Go Molecular!: A Clinical Reference Guide To Molecular Allergy

2021
edition with
information on
novel components
rSes i 1 and
rPru p 7
Go molecular!
A clinical reference guide to molecular allergy
Part 1: The basics
Revised and updated 2nd edition (2021)

Preface
Molecular allergens have been described overview of the important themes within
in scientific literature for well over a decade molecular allergology, especially protein
now, but it has only been in recent years that families, their clinical relevance and
they have been used more routinely in the nomenclature. If there is one important
allergy clinic. aspect to learn in molecular allergology it is
the scientific relevance of protein families,
New technology can be challenging, and as they are the key to understanding clinical
it often requires a period of adjustment molecular allergology.
and adaptation. There are many allergen
components covering many different sources A straightforward summary of the main
and their clinical relevance is continually allergen components, what ImmunoCAP™
emerging year on year. This can make it products are available and an aid to interpret
difficult to remember their relevance. Many test results can be found in part 2 of this
physicians have commented to me that they series – ‘The Allergen Components’.
could do with a simplified ‘all in one guide’ so
I have tried to simplify molecular allergology I hope you find this guidebook series useful.
based on the allergen components Thermo
Fisher Scientific is supplying (manufacturer is Neal Bradshaw
Phadia AB). Portfolio Manager - Allergy
Author of the Go Molecular! books
The intention of part 1 in this guidebook Immunodiagnostics
series is to give a basic introduction to Thermo Fisher Scientific
molecular allergology focusing on plant food
allergy, although other molecular sources
such as venoms and aeroallergens are also
discussed. This guide gives an introductory
Disclaimer:
The content of this book is intended as an aid to the physician to interpret allergen specific IgE antibody test results.
It is not intended as medical advice on an individual level. A definitive clinical diagnosis of IgE mediated allergic disorders should only be made
by the physician based on the clinical history for the individual patient after all clinical and laboratory findings have been evaluated. It should
not be based on the results of any single diagnostic method.
172050.AL.EU, INT, JP1.EN.v1.21
2
Contents
Foreword 4
Introduction: Molecular allergens tell us more 5
Protein families 7
Allergen component nomenclature 9
Specific and cross-reactive allergens 10
Other clinical considerations 11
Food allergy 13
Plant components 17
Interpreting results from cross-reactive protein families 19
Summary of plant food components 21
Plant allergen components in some common foods 24
Other allergen components 26
Immunotherapeutics – Aeroallergens and venoms 36
Common questions regarding molecular components 37
Glossary 39
Educational resources 40
Using ImmunoCAP Allergen Component tests 41
ImmunoCAP Allergen Component list 43
ImmunoCAP ISAC112i Chip Allergen Components 47
3
Foreword
With the advent of allergen components, This edition of this book is very welcome with
allergy has got much more complicated. its updated information about each of the
However whole allergen diagnostics, with various allergen components. Importantly,
skin prick testing or serum specific IgE, their clinical implications are explained
commonly don’t allow us to unravel the allowing us to use information about allergic
complexity that some of our allergy patients sensitization to each individual component to
exhibit. Using allergen components to improve the management of our patients.
understand the molecular allergology of
these complex patients has a real potential Professor Graham Roberts
to improve our clinical decision-making. The Professor of Paediatric Allergy and
use of component resolved diagnostics may Respiratory Medicine
optimize our investigation plans and improve University of Southampton
our diagnoses, management plans and the
advice we give to our allergy patients. All
this though relies on clinicians acquiring an
understanding of molecular diagnostics.
This is a rapidly evolving area with, for
example, the whole peanut allergen suddenly
been replaced by more than 10 individual
components with different clinical impacts.
4
Introduction: Molecular
allergology tells us more
The diagnosis of IgE mediated allergies is
made by the physician based on clinical
history for the individual patient in conjunction
with clinical findings and test results, e.g.
specific IgE sensitization tests such as skin
prick and/or blood tests and sometimes
allergen provocations. Until recently the
sensitization tests in use were based on
extracts of allergen sources, but in the
past years the use of component resolved
diagnosis has become increasingly common
in clinical practice. Molecular allergology
brings a new level of understanding to
physicians who seek to improve on existing
diagnostic technologies1-3.
While traditional extract-based IgE blood

tests measure the “sum” of sensitization to
all protein components in whole allergens,
e.g. peanut, molecular allergology makes it Figure 1: Illustration of the common
possible to investigate important individual misconception that there is one IgE antibody
produced by the human body for a whole peanut
proteins within a peanut for specific IgE allergen.
sensitization. IgE antibody profiles to these
molecules vary significantly from patient to
patient and they also differ geographically,
due to local differences of exposure1-3.
Molecular diagnostics reveals more factual

information about what a patient is allergic
to, as individual proteins and profiles can
indicate different clinical characteristics1-3.
5
The IgE indicated in yellow is directed against
peanut Ara h 2*. This can be measured using
ImmunoCAP Allergen Components.
Ara h 2 is the most allergenic protein in

peanuts. Patients positive to it are at high risk
of systemic reactions1-3
Other specific IgE antibodies are directed

against lower risk peanut proteins such as
Ara h 8 and Ara h 5. Proteins closely related
to these are also found in tree and grass
pollen.
Figure 2: Illustration of the reality that there are lots of different IgE antibodies produced
which bind to individual proteins in peanut, like Ara h1, Ara h 2 and Ara h 8.
Ara h 2/Ara h 6 are the proteins that seems to have the highest allergenic potential of all proteins in peanut.
Antibodies produced by patients in response to specific allergen proteins can be measured using single or
multiplex allergen component tests, indicating the patients’ immunological response in their current allergy
status. High levels of IgE to Ara h 2/Ara h 6 will often indicate a patient at high risk of systemic symptoms if
peanuts are eaten1-3.
*ImmunoCAP Allergen f423, Allergen component rAra h 2 Peanut
Clinical relevance
Allergen component diagnostics measures Immunotherapy (AIT) – useful for example
IgE to specific allergen components, in venom and aero-allergy patient
uncovering additional information about an selection1-3.
underlying allergy. Not only do they indicate 3. Understanding cross-reactions between
specific allergen reactivity in the way that species – helping to understand multiple
whole extracts do but they are also sensitizations e.g. in pollen
indicators for: food syndrome1-3.
1. Understanding patient risk for allergic The intention of this first guidebook is to
reactions – adding confidence to your give the physician, dietician or scientist
assessment1-3. a background to molecular allergology.
2. Aiding the selection of the proper A straightforward summary of allergen
treatment extract of Allergen Specific components and an aid to interpretation of
results can be found in part 2 of this series.
6
Much of the clinical value of testing with References
1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide.
allergen components up to now has been
Pediatric allergy and immunology: official publication of the
demonstrated within food allergy, especially European Society of Pediatric Allergy and Immunology. 2016;27
with plant foods such as nuts, fruits and Suppl 23:1-250.
legume seeds. The majority of information 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
Diagnostics. Innovation for a Better Patient Management.
in this reference guide therefore focuses Springer International Publishing Switzerland 2017. ISBN
on food allergen components, although an 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook),DOI
10.1007/978-3-319-42499-6.
overview of other allergen components which
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
provide clinical value, such as those in pollen, document on molecular-based allergy diagnostics. World Allergy
furry animals, mites, latex and insect venoms, Organ J. 2013 Oct 3;6(1):17.
is also included.
Protein families
Introducing testing with molecular allergens related family number 10 proteins). Lipocalins
into daily clinical practice will help improve and serum albumins are examples of
diagnosis of allergy based on allergenic protein families found in mammalian allergen
proteins and protein families. sources1-8.
Protein families referred to in this guide are Below is an example showing the IgE test
families with similar functions and structures results of a patient with suspect plant
found in many allergen sources1-8. For food allergy.
example, plant seeds contain storage
proteins such as vicilins, transport proteins The below test results could be interpreted
such as lipid transfer proteins and defense in three different ways:
proteins such as PR-10s (pathogenesis-
IgE test results of a patient with suspect plant food allergy
Bet v 1 (Birch PR-10) 42.9 kUA/L

Cor a 1 (Hazelnut PR-10) 25.7 kUA/L
Mal d 1 (Apple PR-10) 22.8 kUA/L
Ara h 8 (Peanut PR-10) 12.8 kUA/L
7
• Traditional thinking: four different specific This may also be true for one individual
IgE reactions to four different plant sources. patient at different occasions due to presence
• On the molecular level: IgE to one protein or absence of reaction promoting
family group, i.e. PR-10 allergy – also cofactors 1-3.
indicating cross-reactive IgE.
• The patient is also likely to be sensitized to Always consider test results in
other PR-10 proteins not measured. From association with a clinical history.
the above extrapolations can be made
of other PR-10 sensitization and may be References
relevant to the patient’s clinical history to 1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide.
other allergens, e.g. almond contains PR- European Society of Pediatric Allergy and Immunology. 2016;27
10 proteins. Suppl 23:1-250.
• This same way of thinking can for example 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
be applied to profilin or nsLTP (lipid transfer
Springer International Publishing Switzerland 2017. ISBN
protein) profiles (if positive). 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
More on protein families and their clinical 3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
document on molecular-based allergy diagnostics. World Allergy
relevance will be discussed later in this guide. Organ J. 2013 Oct 3;6(1):17.
4. Garcia BE and Lizaso MT. Cross-reactivity Syndrome in Food.
Interpretation of results Allergy 2011;21(3):162-170.
5. Hauser M, et al. – Panallergens and their impact on the allergic
patient. Allergy, Asthma and Clin Immunol 2010;6(1):1.
In this guide, interpretation has been 6. Termi Midoro-Horiuti T, et al. Pathogenesis-related proteins of
simplified as much as possible in terms of proteins of plants as allergens. Ann Allergy Asthma Immunol
presence of specific IgE. The presence of 2001;87:261-271.
7. Egger M, et al. The role of Lipid Transfer Proteins in Allergic
allergen-specific IgE usually indicates a risk
Disease. Curr Allergy Asthma Rep 2010;10:326-335.
of allergy symptoms and a result of ≥0.1 8. Sicherer SH. Clinical implications of cross-reactive food allergen.
kUA/L indicates sensitization. Some J Allergy Clin Immunol 2001;108(6):881-890.
molecular allergens are associated with
a higher risk for systemic reactions, while
others are considered to pose no or a very
low probability for severe reactions. A high
IgE-level to an allergen such as Ara h 2 or
Cor a 14 often means a high risk of
symptomatic allergy1-3.
However for different patients identical results

for the same allergens may not be associated
with clinically equivalent manifestations, due
to differences in individual patient sensitivities.
8
Allergen component
nomenclature
The WHO/IUIS Committee
Allergen and allergen components are Thermo Fisher Scientific, the leading supplier
identified and categorized by a joint (Phadia AB is the manufacturer) of allergen
partnership of The World Health Organization components, also gives the test a prefix ‘n’
(WHO) and The International Union of for native sourced allergen proteins or an ‘r’
Immunological Sciences (IUIS). The WHO/ for recombinant sourced allergen proteins
IUIS Allergen Nomenclature Sub-committee that are used in the IgE tests.
is responsible for maintaining and developing
a unique, unambiguous and systematic You can look up all WHO IUIS recognized
nomenclature for allergenic proteins. The allergens at allergen.org.
systematic nomenclature is based on
the Linnaean system and is applied to all References
allergens1. For further information check 1. Radauer C et.al. Update of the WHO/IUIS Allergen Nomenclature
Database based on analysis of allergen sequences. Allergy
the IUIS allergen nomenclature website at: 2014; 69: 413–419.
allergen.org.
Allergen components are given a name

based on an abbreviation of the Latin name
of the allergen source (the first three letters of
the first word and first letter of the second).
The allergen protein is also given a number
based on the order of discovery (when
registered/approved by the IUIS committee)1.
An example of peanut allergen component
nomenclature:
Peanut – Arachis hypogaea – Ara h 2
9
Specific and cross-reactive
allergens
Molecular allergens can be split into allergens For instance, dog, cat and horse all contain
with high and low potential for triggering members of the lipocalin protein family
clinical symptoms. These allergens can together with serum albumin which is also
then also be further grouped into molecules found in milk. Birch, grass and weeds contain
specific to an allergen source and molecules profilins, which are found in legumes such
with great similarities even between distantly as soy and peanut, as well as in wheat
related allergen sources. Such allergens and hazelnut. IgE cross-reactions can
are said to be cross-reactive. Differentiating confound extract based test results, which
between sensitization to specific and cross- makes it difficult to understand what the
reactive allergen components helps us to primary allergen causing the symptoms is.
better understand the characteristics of an ImmunoCAP Allergen Component tests
individual’s allergy profile1-3. and the multiplex ImmunoCAP ISAC help to
improve diagnostic clarity1-3.
The below figure demonstrates a typical
allergen test panel. Many of the allergens
could give rise to IgE cross-reactions.
Figure 3: Illustration of a typical allergen test profile
Cat Dog Horse Birch Grass Weed Mite Mould
Egg Fish Milk Hazelnut Peanut Soy Wheat
10
You can learn more about the significance of 3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
these types of allergens at: allergyai.com. document on molecular-based allergy diagnostics. World Allergy
Organ J. 2013 Oct 3;6(1):17.
This website contains an educational course

which describes the basics of molecular
allergy and includes patient case examples.
References
European Society of Pediatric Allergy and Immunology. 2016;27
Suppl 23:1-250.
2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
Springer International Publishing Switzerland 2017. ISBN 978-
3-319-42498-9 ISBN 978-3-319-42499-6 (eBook),
DOI 10.1007/978-3-319-42499-6.
Other clinical considerations

Allergen load A patient sensitized to several allergen
The patient’s clinical history remains the sources will often be sensitized to several
most important part of allergy diagnosis. allergen components. This will contribute to
Component testing will reveal crucial the overall allergen load. For example, if a
information but as with any IgE test it should patient is positive to multiple peanut storage
be used in support of the clinical history. Only components such as Ara h 1, Ara h 2 and
the clinical history can reveal how much of Ara h 3, he or she is likely to have a higher
each food allergen the patient has ingested. IgE load and therefore possibly be at more
For example, when consuming large amounts risk for severe reactions than someone who
of allergens at the same time, such as when is mono-sensitized1-5.
drinking a soy milk drink can affect the
symptom outcome1-3. Diagnostic performance
Extract-based tests (whole allergens) contain
Low risk allergens such as PR-10 proteins a mix of many different proteins from an
found in soy milk, when consumed in great allergen source (e.g. peanut) and measure
amounts can provoke more serious allergy the sum of IgE antibodies to these, which
symptoms in some patients (such as drinking gives high sensitivity, but sometimes can
soy milk1-2). create difficulties in interpretation of results1-5.
11
ImmunoCAP Allergen Component-based For example in food allergy, circulating IgE
tests, both singleplex and multiplex, contain antibodies may remain undetectable despite
pure proteins, measure only specific IgE to a convincing clinical history. The antibodies
single molecules and give results with high may be directed towards allergens that
diagnostic specificity1-5. are revealed or altered during industrial
processing, cooking or digestion and
Allergen component tests therefore have therefore do not exist in the original food for
technical diagnostic superiority at measuring which the patient is tested1-2.
IgE to important individual proteins of interest,
such as to Ara h 2 in peanut or Cor a 14 in Limitations of ImmunoCAP products test
hazelnut. They simply measure IgE specific to results:
one protein and offer reliable results in terms
of minimal variation – like all ImmunoCAP Samples with results below limit of
products. However, it must be remembered quantitation obtained with ImmunoCAP
that a test with allergen components only Allergen Components are recommended
measures one type of specific IgE and that to be tested with the corresponding
most patients will have IgE antibodies to extract based ImmunoCAP Allergen and/
several molecules contained in the or additional relevant ImmunoCAP Allergen
allergen source1-5. Components, if not already performed
and a clinical indication is present. The
Presence of allergen specific IgE implies a extract based testing can cover additional
risk of allergic disease and its significance allergen components present in the allergen
must be evaluated within the clinical source material to which the patient
context. Generally the higher the level of IgE may be sensitized, but which are not
antibodies the higher the probability of a presently available as ImmunoCAP Allergen
clinically manifest allergic reaction1-5. Components or in ImmunoCAP ISAC.
However, for different patients identical A result below limit of quantitation obtained
results for the same allergens may not with an extract based ImmunoCAP Allergen
be associated with clinically equivalent never excludes the possibility of obtaining
manifestations, due to differences in measurable concentrations of specific IgE
individual patient sensitivities. This may also when testing with ImmunoCAP Allergen
be true for one individual patient at different Components from the same allergen source.
occasions due to presence or absence of This is due to the fact that some components
reaction promoting cofactors1-5. may be present in very low amounts in the
natural extract.
Absence of detectable allergen specific IgE
antibodies does not necessarily exclude
the potential for an allergy-like reaction1-2.
12
In most cases it is recommended that testing 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
starts with whole allergens to achieve high
sensitivity to be followed up with allergen document on molecular-based allergy diagnostics. World Allergy
component tests for further specificity and Organ J. 2013 Oct 3;6(1):17.
as an aid in risk assessment if the test for the 4. Wickman M. When allergies complicate allergies. Allergy
2005;60(S79):14-18.
whole allergen is positive1-5.
5. Van Hage M et.al. ImmunoCAP assays: Pros and cons in
allergology. J Allergy Clin Immunol 2017;140:974-7.
Further information at allergyai.com.
References
Suppl 23:1-250.
Food allergy
Food is made up of complex matrices of Fats are metabolized into fatty acids;
natural constituents such as proteins, fats carbohydrates are eventually broken down
and carbohydrates. The way that the human into small sugar molecules, while proteins
body processes food creates by-products of are digested into their constituents - amino
the original food structure. The natural state acids. Most allergens are proteins, made
of proteins can be changed even before we up of amino acid chains, and within these
eat them, most obviously by cooking but also structures are regions called epitopes. It
by storage and processing e.g. liquidizing or is these recognition sites that specific IgE
concentrating (as for fruit juices)1-2. molecules bind to. This can lead to the
release of histamine and other mediators,
There are many different metabolic processes resulting in allergy symptoms1-2.
that occur as soon as food enters the
digestive system. Enzymatic digestion starts
straight away in the mouth; acidic pH and
gastric juices play a role as food enters the
stomach and further digestion takes place in
the gut until the food is absorbed as
smaller nutrients1-2.
13
Unstable labile
proteins cause more
localised reactions
such as OAS
Stable proteins can caused

mixed reactions such as OAS,
other local symptoms and
systemic reactions
Figure 4: An overview of the biological

differences in how allergen proteins
can cause different types of symptoms
Molecules of high allergenic potential mouth, causing less problematic reactions

Some proteins are more resistant than others such as oral allergy syndrome (OAS). As the
to metabolic processes, due to their robust epitope binding regions in these proteins
chemical structures; e.g. storage proteins are destroyed, these molecules tend not to
from peanut (Ara h 1, Ara h 2, Ara h 3 and induce systemic symptoms1-10.
Ara h 6) or ovomucoid from hen’s egg (Gal d
1). As these allergens have higher resistance Allergen profile variability
to digestion, their allergenic potential is also
higher as their epitope structures stay intact If molecules vary in their potential to trigger
longer. As a result, these proteins cause more allergy it raises the question:
systemic symptoms than unstable proteins
(figure 4)1-10. Q: ‘If a patient is IgE tested using a
whole extract (the source) how do you
Molecules of low allergenic potential know which proteins within the source
Certain allergen molecules such as PR- they are sensitized to?’
10s and profilins (present in nuts, fruits A: ‘The simple answer is that a whole
and pollen) are more labile in structure and extract test does not provide all the
therefore susceptible to digestive processes answers!’
such as heating/cooking and enzyme activity
in the gastrointestinal tract. Such labile
proteins start to break down already in the
14
The above question and answer is quite Specific allergens and primary food
thought-provoking. A whole extract IgE test allergy
(the source) is a mixture of lots of individual Identifying IgE to specific molecules often
proteins. It would be impossible to tell indicates the cause of allergy symptoms. In
which proteins a patient is IgE positive to food allergy, the allergens that initially trigger
unless they were separated individually – as the immune system to produce specific
they are when using ImmunoCAP Allergen IgE antibodies are mostly food proteins
Component tests. Also, all patients vary in more resistant to digestion. Such primary
which components they are sensitized to1-10. sensitization to stable proteins is therefore
often associated with systemic allergy
ImmunoCAP offers a large portfolio of symptoms1-10.
different allergen components, enabling the
mapping of individual patient profiles and Cross-reactive sensitization and pollen-
improving diagnostic clarity. ImmunoCAP food syndrome
ISAC is a multiplexing test that measures IgE Allergen components that have highly similar
to a total of 112 allergen components and structures in several different species can
through cross-reactivity one can extrapolate give rise to extensive cross-reactivity, these
sensitizations to other clinically relevant are referred to as “pan-allergens”. Pan-
allergen sources6. allergens are commonly found in plants and
plant derived foods and they can be found
Patients testing positive to a whole extract even in distantly related species such as
(e.g. positive skin prick test to peanut or celery and birch trees1-10.
serum IgE to peanut) can be sensitized to
either allergen proteins of high allergenic Sensitization to pan-allergens may be both
potential or of low/no allergenic potential. By asymptomatic and symptomatic, but the
using molecular diagnostics it is possible to symptoms elicited are often of a milder form,
better differentiate between them, i.e. classify such as OAS. In pollen-allergic patients for
patients into low- and high-risk groups. There instance, IgE antibodies primarily targeted
are of course also cases where the patient towards proteins in pollen (e.g. birch Bet v
is sensitized to both high-risk and low-risk 1) readily cross-react with similar proteins in
allergens and can display symptoms such as food, causing a broad sensitization profile
OAS together with systemic symptoms1-10. which can be considered “secondary” to the
pollen sensitization. In clinical allergy, this is
Furthermore, in a given situation other factors often referred to as pollen-food syndrome
such as amount of allergen, stress, ongoing and in the context of latex, the latex-fruit
infections etc have an impact on the actual syndrome1-10.
clinical reaction1-2.
Cross-reactive allergens exist also in other
sources, such as venoms of stinging insects,
fish, mites and shrimp. For example, dust
15
mite and shrimp share a cross-reactive
protein called tropomyosin1-5.
When sensitization to cross-reactive allergens

is detected, the primary sensitizer should
always be sought after in order to understand
what is driving the patients’ allergy. Using a
range of specific and cross-reactive allergen
component tests it is in most cases possible
to differentiate primary and secondary
reactions1-10.
References
Suppl 23:1-250.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
Organ J. 2013 Oct 3;6(1):17.
4. Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy
2010;40(10):1442-1460.
5. Treudler R. and Simon JC. Overview of component resolved
diagnostics. Curr Allergy Asthma Rep 2013;13(1):110-117.
allergology. J Allergy Clin Immunol 2017;140:974-7.7. Garcia
BE and Lizaso MT. Cross-reactivity Syndromes in Food Allergy. J
Investig Allergol Clin Immunol 2011;21(3):162-170.
8. Zuidmeer L and van Ree R. Lipid transfer protein allergy;
primary allergy/food syndrome in some cases. Curr Opinion Clin
Immunol 2007;7:269-273.
9. Fernándes-Rivas M, et al. Allergies to fruits and vegetables.
Pediatr Allergy Immunol 2008;19:675-681.
10. Santos A and van Ree R. Profilins: Mimickers of Allergy or
Relevant Allergens? Int Arch Allergy Immunol 2011;155:191-
204.
16
Plant components
Plant protein families are shared between and Ara h 6 in peanut and Ber e 1 in Brazil
species; the closer the species are related, nut) are some of the most stable plant food
the more similar the components can be. molecules and therefore the most clinically
This increases the potential for IgE molecules important. The 2S Albumins such as Ara
directed against e.g. pollen allergen epitopes h 2 molecules are not easily destroyed by
to bind to similar allergen epitopes in food. gastric fluids and thus will be immunologically
This immunological mechanism is often the functional in the gastrointestinal tract with
cause for broad sensitization patterns seen the potential to trigger systemic reactions
in many allergic patients. The dominant such as asthma, urticaria, angioedema or
sensitizing plant aeroallergens in Northern anaphylaxis5. Storage proteins are more or
Europe are pollen from birch and temperate less specific to their source and do not cross-
grass species such as Timothy grass, while react except for very closely related allergen
in Southern Europe olive and grass pollen sources (e.g. between legumes such as soy
are the main culprits of hay fever symptoms. and peanut)1-5.
Patients with hay fever may often experience
local symptoms from certain plant-derived LTPs (Lipid Transfer Proteins)
foods, due to cross-reactive proteins LTPs are very stable small molecules
common to different plants1-10. widespread in plant food such as fruits and
nuts. They are found concentrated in the
Plant proteins involved in allergy include skin of Rosaceae fruits, especially in the
storage proteins, LTPs, PR-10s and profilins. peel of peach – the pulp contains less of the
Another type of molecular structure to allergen. LTPs from different species can
take into account is CCDs (cross-reactive be highly cross-reactive. IgE sensitization to
carbohydrate determinants). Further LTPs has mostly been described in Southern
references regarding plant food proteins can Europe, in patients with severe reactions
be found towards the end of this section1-10. to peach and other fruits belonging to the
Rosaceae family (pear, cherry, apple etc.).
Storage proteins LTP allergy has also been described in
Storage proteins are biological reserves connection with nuts such as walnut and
of amino acids used by plants to grow, hazelnut and in peanut1-5, 8.
found in e.g. legumes, seeds and nuts.
Storage proteins are structurally complex The LTP sensitization pattern in Northern
and commonly regarded as much more Europe is not completely understood and not
stable to heat and proteases compared to as well documented as in Southern Europe,
allergens such as PR-10s and profilins. There where LTP sensitization is very common. The
is evidence that 2S albumins (e.g. Ara h 2 protein characteristics of LTPs explain their
17
clinical relevance due to their high resistance enough for testing IgE sensitization to profilin,
to heat and protease digestion. However, due to the close similarity and extensive
LTP sensitization is also associated with local cross-reactivity of this protein group. Profilins
reactions including OAS1-5, 8. from birch (Bet v 2) and/or Timothy grass
(Phl p 12) are often used in measuring IgE
PR-10 (Pathogenesis-Related family to profilin. Profilins are sensitive to heat and
number 10) proteins proteases and will thus primarily give rise
The plant defense proteins of the PR-10 to OAS as the clinical manifestation of food
family are present in pollen of Fagales tree allergy. It is widely accepted that profilins
species (e.g. birch, hazel, alder and beech) have less clinical relevance than PR-10
and can also be found in the pulp of fruit. Bet proteins, although in some cases profilin
v 1 is the major allergen in birch pollen and is sensitization may cause severe reactions1-5, 10.
highly similar to other PR-10 proteins in plant
foods such as Rosaceae fruits (peach, apple CCDs (Cross-reactive Carbohydrate
and cherry etc.), as well as to PR-10s in nuts Determinants)
and legumes. Some molecular structures such as CCDs
are shared between many species and can
In a typical birch allergy scenario, birch pollen be found in insect venoms, pollen and plant
causes a primary sensitization to PR-10 foods. CCDs are not proteins but specific
proteins. This can cause typical hay fever-like parts of carbohydrate chains attached to
symptoms such as an itchy/blocked nose, proteins. The clinical impact of specific IgE
runny eyes etc. to CCDs is considered very low although
As a further consequence, patients who positive IgE test results are frequent1-7.
ingest PR-10 proteins found in nuts or
fruit can react due to IgE cross-reactions. CCDs help us to understand poly-
Food allergy caused via cross-reactivity is sensitization to multiple plant foods and latex
sometimes referred to as secondary food or double positivity between bee and wasp
allergy. Again this is likely to result in local venoms. It is also worth noting that natural
symptoms such as OAS, but depending plant allergen extract preparations contain
on the amount of the cross-reactive protein CCD molecules while recombinant sources
more severe reactions may also occur (e.g. typically are CCD-free and hence more
Gly m 4 induced soy milk reactions)1-5, 9. specific1-7.
Profilin proteins
Profilin proteins occur in many different
plant species and cause broad sensitization
patterns. They are found for example in
pollen (e.g. birch or grass), fruit (e.g. apple,
cherry, melon and banana) and vegetables,
nuts and latex. It has been proposed that
just one profilin from one plant species is
18
References
7. Garcia BE and Lizaso MT. Cross-reactivity Syndromes in Food
Allergy. J Investig Allergol Clin Immunol 2011;21(3):162-170.
European Society of Pediatric Allergy and Immunology. 2016;27 8. Zuidmeer L and van Ree R. Lipid transfer protein allergy;
Suppl 23:1-250. primary allergy/food syndrome in some cases. Curr Opinion Clin
Immunol 2007;7:269-273.
Diagnostics. Innovation for a Better Patient Management. 9. Fernándes-Rivas M, et al. Allergies to fruits and vegetables.
Springer International Publishing Switzerland 2017. ISBN Pediatr Allergy Immunol 2008;19:675-681.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI 10. Santos A and van Ree R. Profilins:Mimickers of Allergy or
10.1007/978-3-319-42499-6. Relevant Allergens? Int Arch Allergy Immunol 2011;155:191-
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus 204.
Organ J. 2013 Oct 3;6(1):17.
2010;40(10):1442-1460.
Interpreting results
from cross-reactive protein
families
Example 1
A variety of allergen component tests could Like all ImmunoCAP Specific IgE tests,
be used when resolving a patient’s birch-food ImmunoCAP Allergen Components give
allergy. Is it a primary food allergy? Bet v 1 is results in kUA/L (ImmunoCAP ISAC gives
a dominating primary sensitizing allergen in a semi-quantitative results in ISU-E). Primary
birch allergic patient and could produce cross- sensitizing allergens from within the same
reactions between other plant food species. protein family (in this example PR-10) will
normally give the highest specific IgE level.
The example below demonstrates a Other secondary IgE sensitizations will give
patient profile of PR-10 sensitization with similar specific IgE readings but normally
a suspected case of IgE-mediated peanut lower levels than the primary sensitizing
allergy. In this example, all other risk allergens allergen due to reduced protein homology
such as Ara h 2 in peanut or Cor a 14 from (and therefore reduced IgE binding)1-6.
hazelnut were IgE-negative.
19
Example 1: PR-10 sensitization with a suspected case of IgE-mediated
peanut allergy

Mal d 1 (Apple PR-10) 22.8 kUA/L
Clinical interpretation: Clinical interpretation:

• Food-pollen syndrome caused by a primary • Primary sensitization to peanut allergens
PR-10 birch-pollen allergy Ara h 1, Ara h 2 and Ara h 3
• Likely symptoms local/mild or none e.g. • Ara h 2 is the most important peanut
oral allergy to hazelnut, peach allergen; the patient is at higher risk of
and peanut severe, systemic symptoms
• The patient also has concomitant birch
“Secondary” reactions due to cross-reactivity sensitization and perhaps other allergy
can occur via plant allergens such as CCDs symptoms such as rhinitis, asthma and oral
and profilins. On the other hand, if a patient itching
has a primary sensitization to an allergen • Food pollen syndrome – caused from a
component that does not cross-react (such primary PR-10 birch-related pollen allergy.
as a storage protein) then this serves as a Likely reactions to these foods are local/
diagnostic marker of risk for severe reactions mild e.g. oral allergy, or none
which is covered further in this guide1-6. • Both systemic and local symptoms
might occur
Example 2
Using the example of suspected peanut
allergy (see figure Example 2 below) the IgE
results could be interpreted like this:
Example 2:
Ara h 1 (Storage protein) 20.8 kUA/L


Pru p 1 (Peach PR-10) 14.8 kUA/L
20
Always use the test results in 5. Treudler R. and Simon JC. Overview of component resolved
combination with a clinical history. The diagnostics. Curr Allergy Asthma Rep 2013;13(1):110-117.
presence of specific IgE is not always
associated with clinical symptoms but
represents a risk of allergic reactions on
allergen exposure.
References
Suppl 23:1-250.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
Organ J. 2013 Oct 3;6(1):17.
2010;40(10):1442-1460.
Summary of plant food

components
Plant protein families are common to many These are storage proteins, LTP, PR-10 and
species and the closer the species are profilin proteins. In addition, CCDs (Cross-
related the more similar the proteins can be. reactive Carbohydrate Determinants) are
But also in distantly related species there are allergenic structures found in pollen and plant
proteins that are very similar which can give food, as well as in insects and venoms1-5.
rise to cross-reactivity. Thus, IgE molecules
directed against pollen allergen epitopes can
bind to similar allergen epitopes in foods such
as peanuts, tree nuts, fruits and vegetables1-5.
The majority of food allergen components in

plants belong to four main protein groups.
21
Protein family Risk for systemic reactions? Do I have to consider many different
allergen sources?
Storage proteins High. Storage proteins are heat and No. Storage proteins are not cross-
digestion stable which explains their ability reactive, except for very closely related
to more often cause systemic reaction in allergen sources (e.g. between legumes
addition to oral allergy syndrome (OAS). such as soy and peanut).
LTP Moderate to High. LTPs are heat and Yes. Partly cross-reactive (the degree of
digestion stable which explains their ability structural similarity varies between LTPs in
to more often cause systemic reaction in plant food and pollen).
addition to OAS.
PR-10 Low. Often cause only local symptoms Yes. Cross-reactive (the degree of
such as OAS due structural similarity varies between PR-10 in
to their sensitivity to heat and digestion, but plant food and birch-related pollen).
a few cases with systemic reactions have
been reported e.g. for soy Gly m 4 and
Celery Api g 1.
Profilin Low. Often have little clinical relevance in Yes. Highly cross-reactive (high degree
allergic diseases. However, profilins may of structural similarity between profilins in
cause local reactions in some patients pollen, plant food and latex).
allergic to plant foods including citrus fruits,
banana and tomato, and a few cases with
systemic reactions have been reported e.g.
for melon and lychee.
CCD Very low. Usually not associated with Yes. Highly cross-reactive (same CCD
clinical reactions but may induce IgE structure in pollen, plant food and venoms).
antibody responses in some patients.
Table References 5. Treudler R. and Simon JC. Overview of component

1. Matricardi PM et al. EAACI Molecular Allergology resolved diagnostics. Curr Allergy Asthma Rep
User’s Guide. Pediatric allergy and immunology: official 2013;13(1):110-117.
publication of the European Society of Pediatric Allergy
and Immunology. 2016;27 Suppl 23:1-250.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook),
DOI 10.1007/978-3-319-42499-6.
document on molecular-based allergy diagnostics. World
Allergy Organ J. 2013 Oct 3;6(1):17.
2010;40(10):1442-1460.
22
Figure 5:
Labile Stable
protein protein
tions
nd reac
re symptoms a
to cau se seve
ing risk
Increas
Risk
Profilin PR-10 Storage

CCDs LTPs
proteins proteins proteins
An overview of the biological differences in how allergen proteins

can cause different types of symptoms
References
1. Matricardi PM et al. EAACI Molecular Allergology
User’s Guide. Pediatric allergy and immunology: official
publication of the European Society of Pediatric Allergy
and Immunology. 2016;27 Suppl 23:1-250.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook),
DOI 10.1007/978-3-319-42499-6.
document on molecular-based allergy diagnostics. World
Allergy Organ J. 2013 Oct 3;6(1):17.
2010;40(10):1442-1460.
5. Treudler R. and Simon JC. Overview of component
resolved diagnostics. Curr Allergy Asthma Rep
2013;13(1):110-117.
23
Plant allergen components
in some common foods
Allergen source/
Storage proteins
Component family Profilin PR-10 LTP 2S Vicilin- Legumin- Other

Albumin like 7S like 11 S
globulin globulin
Peanut Ara h 5 Arah 8 Ara h 9, Ara h 2, Ara h 1 Ara h 3 Ara h 10-
16, 17 6, 7 15
Soy Gly m 3 Gly m 4 Gly m 8 Gly m 5 Gly m 6 Gly m 7
Hazelnut Cor a 2 Cor a 1 Cor a 8 Cor a 14 Cor a 11 Cor a 9
Walnut Jug r 7 Jug r 5 Jug r 3, 8 Jug r 1 Jug r 2, 6 Jug r 4
Pecan Car i 1 Car i 2 Car i 4
Cashew Ana o 3 Ana o 1 Ana o 2
Pistachio Pls v 1 Pls v 3 Pls v 2, 5 Pls v 4
Brazil nut Ber e 1 Ber e 2
Sesame Ses Ses Ses i 3 Ses i 6, 7 Ses i 4, 5
i1 i2
Sunflower seed Hel a 2 Hel a 3 Hel a 2 S

Albumin
Rape seed Bra n 8 Bra n 1 Bra n 4, 7
Cabbage Bra o 8 Bra o 3
Mustard Sin a 4 Sin a 3 Sin a 1 Sin a 2
Buckwheat Fag e 2 Fag e 3 Fag e 4
Kiwi Act d 9 Act d 8, Act d 10 Act d 13 Act d 12 Act d 1,
11 2, 5
Melon Cuc m 2 Cuc m 3 Cuc m 1
Tomato Sola l 1 Sola l 4 Sola l 3, Sola l 2, 5
6, 7
Apple Mal d 4 Mal d 1 Mal d 3 Mal d 2
Pear Pyr c 4 Pyr c 1 Pyr c 3 Pyr c 5
Almond Pru du 4 Pru du 1 Pru du 3 Pru du 6 Pru du 5
Peach Pru Pru
Pru p 4 Pru p 1 Pru p 3
p2 p7
Apricot Pru ar 1 Pru ar 3
Plum Pru d 4 Pru d 1 Pru d 3 Pru d 2, 7
Cherry Pru av 4 Pru av 1 Pru av 3 Pru av 2
24
Available as single ImmunoCAP Available on ImmunoCAP ISAC112i Chip
Bold Bold
Allergen Component only
Normal WHO/IUIS listed Italic Described in peer reviewed literature
Likely but not yet described
Allergen source/
Storage proteins
Component family Profilin PR-10 LTP 2S Vicilin- Legumin- Other

Albumin like 7S like 11 S
globulin globulin
Strawberry Fra a 4 Fra a 1 Fra a 3
Raspberry Rub i 1 Rub i 3
Carrot Dau c 4 Dau c 1 Dau c 3 Dau c 5
Celery Api g 4 Api g 1 Api g 2, 6 Api g 3, 5
Wheat Tri a 12 Tri a 14 Tri a 19,
Gliadin,
many more
Barley Hor v 12 Hor v 15-
17, 20
Rice Ory s 12
Maize Zea m 12 Zea m 14 Zea m 8
Plants often driving sensitization

Birch Bet v 2 Bet v 1
Timothy Phl p 12
Latex Hev b 8 Hev b 12 Hev b 5,
6, 11
References 4. Sastre J. Molecular diagnosis in allergy. Clin Exp

1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide. Allergy 2010;40(10):1442-1460.
Suppl 23:1-250.
www.allergen.org and www.allergome.org
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
Organ J. 2013 Oct 3;6(1):17.
25
Other allergen
components
Allergen Component testing also provides to egg and milk, respectively1,2,5-7.
useful information about other allergen
References
sources such as non-plant foods, furry
animals, mites, molds, pollen and venoms Pediatric allergy and immunology: official publication of the
from stinging insects. Below is a brief European Society of Pediatric Allergy and Immunology. 2016;27
overview, although further information on Suppl 23:1-250.
2. Kleine-Tebbe J and Jakob J Editors: Molecular Allergy
clinical interpretation and what ImmunoCAP
Allergen Components are available can Springer International Publishing Switzerland 2017. ISBN
be found in guidebook 2 – ‘The Allergen 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
Components’. The below is intended as an
introduction to other allergen component document on molecular-based allergy diagnostics. World Allergy
areas, including references below for each Organ J. 2013 Oct 3;6(1):17.
allergen section. 4. Chokshi NY et al. Molecular diagnosis of egg allergy: an update.
Expert Rev Mol Diagn. 2015;15(7):895-906
5. Clark A et al. A longitudinal study of resolution of allergy to well-
Egg and milk cooked and uncooked egg. Clin Exp Allergy 2011;41:706-712.
Foods such as milk and egg are associated 6. Gradman J et al. Relationship between specific IgE to egg
more with pediatric allergy, and children tend components and natural history of egg allergy in Danish
children. Pediatr Allergy Immunol. 2016;27(8):825-830.
to outgrow these allergies at a young age1-7.
7. Nowak-Wegrzyn A et al. Tolerance to extensively heated milk
However, in a recent longitudinal egg allergy in children with cow’s milk allergy. J Allergy Clin Immunol
study in the UK it was shown that many 2008;122:342-347.
children don’t outgrow their egg allergy until

well past 5 years of age, in fact the median Red meat
age in this study was 10 years for egg allergy Recently a previously unrecognized clinical
resolution5. syndrome has been reported where systemic
reactions occur several hours after the
Egg and milk contain allergen components ingestion of mammalian meat (beef, pork,
that are markers for reactivity to different lamb and offal, e.g. kidney)1-8. Most cases
forms of allergy. The allergenicity of hen’s egg have concerned adults, but recent reports
Gal d 1 (Ovomucoid) and cow’s milk Bos d also include children6. Whereas food allergy
8 (Casein) is not destroyed by heating, and symptoms generally occur shortly after
patients negative to Gal d 1 and/or Bos d ingestion, this type of red meat allergy is
8 IgE tests have been observed to tolerate associated with symptoms delayed 3-6
cooked forms of egg and milk1-7. Allergy hours. The most common symptoms include
persistency is associated with IgE to the gastrointestinal problems, urticaria and
same allergens, and therefore IgE to Gal d anaphylaxis1-8.
1 and Bos d 8 can be used as markers of
clinical reactions and tolerance development A carbohydrate, the oligosaccharide
26
Galactose-alpha-1, 3-Galactose (alpha- Shellfish and crustaceans
gal), appears to be the allergen causing the Shellfish and particularly prawns make up
reactions1-8. Alpha-gal is present in many one of the major allergenic food groups1-5.
mammalian proteins including beef, pork Tropomyosin (Pen a 1, Pen m 1) is
and lamb1-2,5. The primary hypothesis in considered a major allergen in shrimp and
the attempts to explain the causes of IgE crustacean allergy1-6. Tropomyosin proteins
antibody responses to alpha-gal is that are highly cross-reactive actin-binding
previous tick bites may be a causative proteins located in muscle fibers amongst
factor1-2,7,8. Measuring specific IgE to alpha- many invertebrate species such as shrimps
gal is a tool that can be used to support the (Pen a 1), and other crustacean foods such
diagnosis of this type of red meat allergy as crab, lobster and molluscs as well as
and also sensitization to the cancer drug dust mites (Der p 10) and cockroaches (Bla
cetuximiab which contains the alpha gal g 7). Due to its wide-spread occurrence,
epitope1-9. tropomyosin can be both inhaled and
ingested. About 10% of dust mite-
References
allergic patients have IgE to tropomyosin.
Some studies suggested that dust mite
European Society of Pediatric Allergy and Immunology. 2016;27 immunotherapy or respiratory exposure
Suppl 23:1-250. to dust mite tropomyosin may induce
tropomyosin sensitization causing food
Springer International Publishing Switzerland 2017. ISBN allergy to shrimps1-3.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6. References
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus 1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide.
document on molecular-based allergy diagnostics. World Allergy Pediatric allergy and immunology: official publication of the
Organ J. 2013 Oct 3;6(1):17. European Society of Pediatric Allergy and Immunology. 2016;27
4. Commins SP et al. Delayed anaphylaxis, angioedema, or Suppl 23:1-250.
urticaria after consumption of red meat in patients with IgE 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
antibodies specific for galactose-alpha-1,3-galactose. The Diagnostics. Innovation for a Better Patient Management.
Journal of allergy and clinical immunology. 2009;123:426-33. Springer International Publishing Switzerland 2017. ISBN
5. Morisset M et al. Anaphylaxis to pork kidney is related to IgE 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
antibodies specific for galactose-alpha-1,3-galactose. Allergy. 10.1007/978-3-319-42499-6.
2012;67:699-704. 3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
6. Kennedy JL, et al. Galactose-alpha-1,3-galactose and delayed document on molecular-based allergy diagnostics. World Allergy
anaphylaxis, angioedema, and urticaria in children. Pediatrics. Organ J. 2013 Oct 3;6(1):17.
2013;131:e1545-52. 4. Leung NYH et al. Current immunological and molecular
7. Van Nunen SA et al. An association between tick bite reactions biological perspectives on seafood allergy: A comprehensive
and red meat allergy in humans. Med J Aust. 2009 May review. Clin Rev Allergy Immunol. 2014;46(3):180-97.
4;190(9): 5. Mariona P et al. Molecular Diagnosis of Shrimp Allergy:
510-1. Efficiency of Several Allergens to Predict Clinical Reactivity. J
8. Hamsten C et. al. Identification of galactose-alpha-1,3- Allergy Clin Immunol: In Practice 2015;3(4):521-529.
galactose in the gastrointestinal tract of the tick Ixodes ricinus; 6. Gamez C, et al. Tropomyosin IgE positive results are a good
possible with red meat allergy. Allergy. 2013;68(4):549-52. predictor of shrimp allergy. Allergy 2011;66:1375-1383.
9. Chung CH et al. Cetuximab-induced anaphylaxis and IgE specific
for galactose-α-1,3-galactose. NEJM. 2008;358 (11):1109-17.
27
Fish Furry Animals
Parvalbumins such as Gad c 1 (cod, white Furry animals such as dogs, cats and
fish) and Cyp c 1 (carp) are major fish horses produce some of the most prevalent
allergen components and markers of fish allergens in our environment and are released
sensitization1-6. Fish-allergic patients can into the surroundings through animal saliva,
sometimes tolerate certain fish species while dander and urine. Like many other allergen
reacting to others. However, as parvalbumins sources furry animals contain both specific
from different fish species are structurally and cross-reactive allergen components1-3.
closely related and highly cross-reactive,
analysis of IgE antibody binding to them Clinically uteroglobin and lipocalins have
is generally not informative in regard to been identified as the most important
discriminating between allergies to different major allergen components from cat, dog
species of fish. A positive test result to and horse1-7. Serum albumins are often
either of Gad c 1 and Cyp c 1 nevertheless considered to have less clinical relevance
indicates a risk of severe reactions to fish1- in allergy to furry animals, they are minor
6
. Parvalbumins are expressed in lower allergens which cause multiple positivity due
amounts in certain fish species such as tuna, to cross-reactivity when using extract tests1-3.
swordfish and some mackerels. This perhaps However serum albumins are important food
explains why some fish-allergic patients can allergens in meat1-3,8.
tolerate these species4-6.
Children with problematic severe asthma
References often have higher levels of IgE antibodies
1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide. towards cat, dog and horse compared with
children with controlled asthma5-6. Revealing
Suppl 23:1-250. the primary allergen source driving the allergy
2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy could help improve allergy management such
as allergen reduction/avoidance strategies,
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI and be an aid to select the proper Allergen
10.1007/978-3-319-42499-6. Specific Immunotherapy (AIT). AIT success
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus is more likely if sensitization to specific
Organ J. 2013 Oct 3;6(1):17. components is identified and appropriate
4. Sharp MF and Lopata AL. Fish Allergy in Review. Clin Rev Allerg therapy administered3,9-10.
Immunol 2014;46:258-271.
5. Griesmeier U et al. Expression levels of parvalbumins determine References
allergenicity of fishspecies. Allergy 2010;65:191-198.
6. Kuehn A. Fish Allergens at a Glance: Variable Allergenicity of Pediatric allergy and immunology: official publication of the
Parvalbumins, the Major Fish Allergens. Front Immunol. 2014; European Society of Pediatric Allergy and Immunology. 2016;27
5:179. Suppl 23:1-250.
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10.1007/978-3-319-42499-6.
28
60-70% of pet sensitized patients are sensitized to serveral pet extracts
- specific or due to cross-reactivity sensitization11
Typical allergens12
Fel df 11
Can Can f 2
Fel d 1 Fel d 4 Fel d 7 Fel d 2 Fel df 14

Can Can f 6 Can f 5 Can f 3 Fel dc 11 Equ c 3
Equ
Cat Dog Horse
Specific components in squares
Uteroglobin Lipocalin family Kallikrein Serum albumins
Protein family Summary Clinical Importance
Uteroglobin Uteroglobin, a steroid-inducible High. Fel d 1 the major cat allergen

cytokine-like molecule with anti- belongs to this family.
inflammatory and immunomodulatory
properties.
Lipocalin family Small, specific molecules. Although High. Lipocalins are often major
highly conserved they display limited allergens and constitute an important
sequence identity of between 20 – primary allergen.
30%.
Kallikrein Kallikreins are peptidases. Prostate High. Associated with male dogs
specific antigen (PSA) is a kallikrein (Can f 5). A major allergen.
which liquefies semen and allows
sperm to swim freely.
Serum albumin Large globular proteins present in High. Highly cross reactivity, minor
dander, saliva, meat and milk. allergen and is seldom of clinical
importance.
29
Furry Animals (continued)
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus for a long time been known to be major mite
specific allergens1-4. Recently several other
Organ J. 2013 Oct 3;6(1):17.
4. Hilger C et al. Animal Lipocalin allergens, Curr Allergy Asthma
mite allergens have been identified and Der
Rep 2012;12 438 – 447 p 23 has been recognized as also being
5. Konradsen JR et al. Severe childhood asthma and allergy to a major mite component with high clinical
furry aninmals: Refined assessment and using molecular based
relevance5-6. Sensitization to increasing
allergy diagnostics. Pediatr Allergy Immunol 2014: 25: 187 -
192. numbers of mite components seem to
6. Nordlund B et al. IgE antibodies to animal-derived lipocalin, indicate more severe disease6.
kallikrein and secretoglobin are markers of bronchial
inflammation in severe childhood asthma. Allergy 2012;67:661-
669. Tropomyosin (Der p 10) is the main cross-
7. Cosme-Blanco W et.al Anaphylaxis to Horses and Epinephrine reactive allergen between mites, shellfish,
Use: Increasing Awareness Among Pediatric Patients and cockroaches and helminths. Tropomyosin is a
Families. Pediatr Allergy Immunol 2017 ;28(6):608-610.
minor allergen in mite allergy but considered
8. Werfel SJ. Clinical reactivity to beef in children allergic to cow’s
milk. J Allergy Clin Immunol 1997 99(3):293-300. a major allergen in shellfish allergy1-3.
9. Asero R. Component-resolved diagnosis-assisted prescription
of allergen-specific immunotherapy: a practical guide Eur Ann References
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10. Schmid-Grendelmeier et al. Recombinant allergens – routine Pediatric allergy and immunology: official publication of the
diagnostics or still only science? Der Hautarzt 2010;61(11):946- European Society of Pediatric Allergy and Immunology. 2016;27
953 Suppl 23:1-250.
11. Borres MP et al. Use of allergen components begins a new era 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
in pediatric allergolog. Pediatr Allergy Immunol. 2011;22:454- Diagnostics. Innovation for a Better Patient Management.
61. Springer International Publishing Switzerland 2017. ISBN
12. Konradsen W, et al. Allergy to furry animals: New insights, 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
diagnostic approaches, and challenges. J Allergy Clin Immunol. 10.1007/978-3-319-42499-6.
2015;135:616-25. 3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
Organ J. 2013 Oct 3;6(1):17.
House dust mites 4. Calderon MA et al. House Dust Mite Respiratory Allergy: An
Allergy to house dust mites (HDM) is a main Overview of Current Therapeutic Strategies. The journal of
allergy and clinical immunology In practice. 2015;3(6):843-55.
cause of respiratory allergies in most parts
5. Posa D et al. Evolution and predictive value of IgE responses
of the world, and exposure to HDM is a toward a comprehensive panel of house dust mite allergens
major trigger of asthma exacerbations1-4. during the first 2 decades of life. J Allergy Clin Immunol
2017;139 :541.
Dermatophagoides pteronyssinus (Der p)
6. Resch Y et.al. Different IgE recognition of mite allergen
and Dermatophagoides farinae (Der f) are components in asthmatic and non-asthmatic children. J Allergy
the most common HDM species, both Clin Immunol. 2015;136(4):1083-91.
containing the major allergens - group 1 and
2 proteins. The homology between the two
mite species is very high and cross-reactions Pollen
are common1-3.
Grasses
Der p 1/Der f 1 and Der p 2 /Der f 2 have All grasses belong to the same botanical
30
family, Poaceae, therefore cross-reactivity Organ J. 2013 Oct 3;6(1):17.
between different species is common and the 4. Andersson K. et al. Characteristics and immunobiology of grass
closer the relations (e.g. within subfamilies), pollen allergens. International Archives of Allergy & Immunology.
2003; 130(2): 87–107.
the higher the degree of cross reactivity1-4.
5. Barber D. et al. Understanding patient sensitization profiles
Grass pollen allergy is common worldwide, in complex pollen areas: a molecular epidemiological study.
and many atopic patients show sensitization Allergy. 2008 Nov;63(11):1550–8.
to grass pollen1-6. Grass pollen season 6. Hatzler L et al. Molecular spreading and predictive value of
preclinical IgE response to Phleum pratense in children with hay
overlaps with weed pollen such as mugwort fever. J Allergy Clin Immunol. 2012 Oct;130(4):894–901 e5.
and ragweed in most parts of Europe and 7. Hauser M et al. Panallergens and their impact on the allergic
with tree pollen (olive, plane) in Southern patient. Allergy Asthma Clin Immunol. 2010; 6(1):1.
Europe 1-3,5. Group 1 and group 5 allergens

(e.g. Phl p 1 and Phl p 5 from Timothy) Trees
are dominating grass pollen allergens and Opposed to grasses, trees belong to several
markers of primary sensitization in a majority different botanical families, often even to
of patients1-6. Sensitization to Phl p 1 usually different orders, and there is less cross-
precedes other grass pollen component reactivity between specific tree allergens.
sensitizations in the development of hay fever However all tree pollen contain profilin and
symptoms6. In warmer areas, other grass most contain polcalcins and CCDs, giving
species such as Bermuda grass are common rise to possible cross-reactivity on the extract
and they also contain group 1 allergens e.g. level1-8.
Cyn d 11-5. Sensitization to cross-reactive
allergens such as profilin (Phl p 12) and Due to Bet v 1 sensitization (the major birch
polcalcin (Phl p 7) is usually not frequent but allergen) many birch pollen allergic patients
several grass allergens carry CCD which react to several pollen, such as the closely
can cause cross reactivity in extract based related alder, hazel, beech and oak1-3,6.
testing1-7. In addition, many of these patients have
concomitant pollen-related food allergies due
When no specific grass sensitization is to PR-10 cross-reactivity (Bet v 1) and may
detected other pollen or food specific react to various fruits, nuts and vegetables
components should be investigated1-3,5. (e.g. apple, pear, cherry or hazelnut)1-3. In
most cases, symptoms are restricted to oral
References reactions and the food is often tolerated
1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide. when cooked since PR-10 allergens are heat
labile1-3.
Suppl 23:1-250.
2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy Olive and ash are botanically very closely
related (Oleaceae family) and there is
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI extensive cross-reactivity between these
10.1007/978-3-319-42499-6.
31
species1-5,7. Olive tree pollen allergy is quite Cha o 1) and Japanese cedar (Cry j 1) and
common and is one of the most important there is an extensive cross-reactivity between
causes of seasonal respiratory allergy species1-4,8,9.
in the Mediterranean area5,7. Ole e 1 is
the major marker for primary olive pollen References
sensitization1-5,7. The European ash (Fraxinus 1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide.
excelsior) is common in most of Europe but European Society of Pediatric Allergy and Immunology. 2016;27
ash tree pollen may often be overlooked as Suppl 23:1-250.
a cause of pollinosis1-2,5. Ole e 1 serves as a 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
very good marker allergen for ash due to the
high cross reactivity1-5,7. 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
Plane trees are known as “street trees” and 3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
are found planted practically anywhere in the Organ J. 2013 Oct 3;6(1):17.
world1-2. Recombinant Pla a 1 is a specific 4. Asam C et al. Tree pollen allergens - an update from a
marker allergen discriminating between molecular perspective. Allergy 2015:70:1201-1211.
genuine plane tree pollen sensitization and 5. Barber D et al. Understanding patient sensitization profiles
in complex pollen areas: a molecular epidemiological study.
cross-reactivity1-5. Pla a 3 is a LTP which Allergy. 2008 Nov; 63(11): 1550–8.
cross-reacts with other LTPs in e.g. fruits1-3. 6. Hauser M et.al. Bet v 1-like pollen allergens of multiple Fagales
Pla a 3 is presently not available as a single species can sensitize atopic individuals. Clinical & Exp Allergy.
2011; 41:1804–181.
ImmunoCAP Allergen Component. However,
7. Rodríguez R, et al. Olive pollen recombinant allergens: value in
Pla a 3, as well as the diagnosis and immunotherapy. J Investig Allergol Clin Immunol
plane-tree specific and major allergen Pla a 2007;17 Suppl 1:4–10.
1 are available on the ImmunoCAP ISAC112i 8. Charpin D et al .Cypress Pollinosis: from Tree to Clinic. Clin Rev
Allergy Immunol. 2017 Apr 11
Chip.
9. Douladiris N et al. A molecular diagnostic algorithm to guide
pollen immunotherapy in Southern Europe: towards component
Cypresses and cedars are common resolved management of allergic diseases. Int Arch Allergy
Immunol 2013;162;163-172.
ornamental trees1-5. There are several
species of cypress and cedars and since
they are closely related cross-sensitization is Weeds
extensive. Cypress trees bloom in the winter Weed allergy diagnosis can be unclear
and may cause winter respiratory allergy and difficult to make due to frequent poly-
which is often misdiagnosed since symptoms sensitizations and inconclusive anamnesis
are occurring during winter and are very because of overlapping flowering seasons
similar to perennial allergies like dust mite with other pollen such as birch and grass1-3.
allergy1-3,8,9. Cup a 1 is a specific marker for Cross reactions are expected between
primary sensitization to Cupressaceae pollen. different weed species when botanically
The Cup a 1 allergen is very similar to major closely related, however many weeds belong
allergens of Mediterranean cypress (Cup s 1) to unrelated botanical families and therefore
Mountain cedar (Jun a 1) Japanese cypress specific marker allergens are available,
32
e.g. Amb a 1 from Ragweed, Art v 1 from Molds
Mugwort, Par j 1 from Parietaria, Pla l 1 from There is current evidence to demonstrate
English plantain and Sal k 1 from Saltwort1-5. a close association between fungal
Saltwort is a weed common in dry, semi- sensitization and asthma severity1-5. Many
arid areas and is becoming more and more airborne fungi are involved such as Alternaria,
common in southern parts of Europe due to Aspergillus, Cladosporium and Penicillium,
climate change. and exposure may be indoors, outdoors
or both. Fungal sensitization is common
Apart from profilin and CCDs, mugwort in asthmatic patients and the term “severe
and ragweed pollen contain some other asthma with fungal sensitization” (SAFS) has
cross-reactive allergens. Cross-reactive IgE been proposed1-5. However, it is recognised
antibodies can lead to clinically significant that enhanced and precise definition of fungal
allergic reactions5. sensitization will require improvements in
diagnostic testing and this can be facilitated
Pollen-food syndromes driven by weed by component testing1-9.
pollen are mainly generated by mugwort and
ragweed pollen. In addition to Oral Allergy Alternaria alternata is a major outdoor as
Syndrome (OAS) more severe allergy is well as indoor aeroallergen in many parts
reported such as the celery-mugwort-spice of the world. Sensitivity to Alternaria has
syndrome1-2,6. been increasingly recognized as a risk factor
for the development and persistence of
References asthma, asthma severity, and potentially fatal
1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide. asthma exacerbations2-6. Alt a 1 is the major
Alternaria allergen. Alt a 1 is considered a
Suppl 23:1-250. specific marker of primary sensitization to
2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy Alternaria Alternata and useful in asthma
diagnostics2-6.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6. Aspergillus fumigatus is an opportunistic
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus fungus causing allergic and invasive
Organ J. 2013 Oct 3;6(1):17. aspergillosis in humans and animals1-4,7-9
4. Gadermaier G et al. Allergens of weed pollen: An overview on Genuine A. fumigatus sensitization is not
recombinant and natural molecules. Methods 2014;66;55-66. always easily identifiable and IgE sensitization
5. Asero R et al. Concomitant sensitization to ragweed and tests are used as part of routine workup
mugwort pollen: who is who in clinical allergy? Ann Allergy
Asthma Immunol 2014;113:307-313. for diagnosing Allergic Bronchopulmonary
6. Egger M et al. Pollen food syndromes associated with weed Aspergillosis (ABPA). The use of allergen
pollinosis: an update from the molecular point of view. Allergy components for A. fumigatus can aid
2006;61:461-476.
the identification of primary A. fumigatus
sensitization1-4,7-9.
33
Asp f 1, Asp f 2 and Asp f 4 are species Venoms
specific allergens while Asp f 3 and Asp f 6 Many patients with suspected honey bee
are described as cross-reactive allergens1,2,7-9. and/or common wasp specific IgE test
Recent studies investigating ABPA positive to both species when using extract
demonstrated that ImmunoCAP Allergen testing. True double allergic reactivity to both
Components could differentiate ABPA from bee and wasp is not clinically common. In
asthma and sensitised patients. ABPA has many cases double venom IgE positivity can
been particularly linked to Asp f 4 and Asp p be caused by cross-reactions to CCDs1-5.
67-9 – see book 2 for further details. Recombinant venom components do not
carry CCD and therefore provide greater
References diagnostic specificity, useful when making
1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide. decisions such as to start AIT1-7. Ves v
1 and Ves v 5 are major allergens from
Suppl 23:1-250. common wasp and Pol d 5 is a marker for
2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy sensitization to paper wasp. The picture for
honey bee sensitivity seems more complex
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI than for wasp and can involve more varied
10.1007/978-3-319-42499-6. sensitization patterns to major components.
3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus Api m 1, Api m 2, Api m 3, Api m 5 and Api
Organ J. 2013 Oct 3;6(1):17. m 10 are all major allergens within bee venom
4. Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy allergy. It has recently been shown that using
2010;40(10):1442-1460. an increasing number of bee components
5. Medrek SK et.al. Fungal sensitization is associated with can improve diagnostic sensitivity1-7.
increased risk of life-threatening asthma. J Allergy Clin Immunol
Pract. 2007;5:1025-31. Low level specific IgE below 0.35 kUA/l can
6 Kustrzeba-Wójcicka I et.al Alternaria alternata and its allergens: be relevant when using components and may
a comprehensive review. Clin Rev Allergy Immunol. 2014 be indicative of venom allergy, so measuring
Dec;47(3):354-65.
down to 0.1 kUA/l can be important1,6.
7. Fukutomi Y et al. Serological diagnosis of allergic
bronchopulmonary mycosis: Progress and challenges.
Allergology International 65 (2016) 30e36. Patients with suspected venom allergy should
8. Bowyer P et al. Relative reactivity of Aspergillus allergens used also be tested with ImmunoCAP Tryptase5,8-9.
in serological tests Medical Mycology September 2006;44, S23
-S28. Patients with high basal levels of tryptase
9. Tanimoto H et al. Molecular-based allergy diagnosis of should be investigated for mastocytosis since
allergic bronchopulmonary aspergillosis in Aspergillus these patients have higher risk for severe
fumigatus-sensitized Japanese patients Clin Exp Allergy.
2015 2015;45,1790–1800 + erratum Clin Exp Allergy reactions during venom immunotherapy5,8-9.
2016;46(2):381.
References
Suppl 23:1-250.
34
2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy allergy1-6. Sensitization to these components
is frequent in surgery-related latex-allergy,
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI especially among children having undergone
10.1007/978-3-319-42499-6 multiple and extensive surgery, such as those
with spina bifida. Sensitization to Hev b 5
Organ J. 2013 Oct 3;6(1):17. and Hev b 6 is associated with occupational
4. Spillner E. et al., Hymenoptera allergens: from venom to exposure to latex e.g. in healthcare workers
”venome”. Frontiers in immunology 2014;5:1-7. and food-handling personnel using latex
5. Biló B, et al. EAACI Interest Group on Insect Venom
gloves1-5. Latex allergens Hev b 8 (profilin)
Hypersensitivity. Diagnosis of Hymenoptera venom allergy.
Allergy 2005;60:1339-1349. and Hev b 6 can be used for examining
6. Kohler et al. Component resolution reveals additional major cross-reactivity to pollen and plant foods,
allergens in patient’s with honeybee venom allergy. J Allergy Clin respectively1-4. If an exclusive sensitization to
Immunol 2014;133:1383-9.
7. Korosec P et al. High sensitivity of CAP-FEIA rVes v 5 and rVes v
the profilin Hev b 8 is seen, allergic symptoms
1 for diagnosis of Vespula venom allergy. J Allergy Clin Immunol. to latex are hardly to be expected5,6.
2012 May;129(5):1406-8.
8. Bonifazi F et al. and EAACI Interest Group on Insect Venom
References
Hypersensitivity. Prevention and treatment of hymenoptera
venom allergy: guidelines for clinical practice. Allergy 1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide.
2005;60:1459-1470. Pediatric allergy and immunology: official publication of the
9. Bonadonna P. et al., Clonal mast cell disorders in patients with
Suppl 23:1-250.
systemic reactions to Hymenoptera stings and increased serum
tryptase levels. J Allergy Clin Immunol 2009;123:680-6. 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
Latex 10.1007/978-3-319-42499-6.
Primary latex allergy should be identified 3. Canonica GW et.al. A WAO - ARIA - GA²LEN consensus
using specific allergen components as Organ J. 2013 Oct 3;6(1):17.
many positive extract test results arise as a 4. Garnier L et al. Molecular allergens in the diagnosis of latex
result of cross-reactive pollen sensitization allergy. Eur Ann Allergy Clin Immunol 2012;44(2):73–79.
involving profilin, CCDs or PR-10 allergens1-6. 5. Ebo DG, et al. Component-resolved diagnosis from latex allergy
by micro-array. Clin Exp Allergy 2010;40(2):348-358.
The association of latex allergy and allergy 6. Schuler S, et al. Microarray-based component-resolved
to plant-derived foods is referred to as the diagnosis of latex allergy: isolated IgE-mediated sensitization to
latex-fruit syndrome and includes a large Latex profilin Hev b 8 may act as confounder. Clin Transl Allergy
2013;3:11.
number of plant foods such as avocado,
banana, chestnut, kiwi, peach, tomato,
potato and bell pepper. The latex allergen
Hev b 6 is considered the main culprit in this
syndrome1-2.
IgE antibodies to Hev b 1, Hev b 3, Hev b

5 and Hev b 6 are markers for primary latex
35
Immunotherapeutics –
Aeroallergens and venoms
Understanding cross-sensitization and Many patients with suspected venom allergy
identifying the right allergen source can be positive for both bee and wasp
Clinically it is obviously important to whole allergens. Double positivity can be
correctly identify the allergen source causing caused by CCDs rather than true double
symptoms before starting immunotherapy sensitization1-3,8-11. ImmunoCAP recombinant
and this is not always easy1-6. Patients can be venom components are CCD-free, which
cross-sensitized to several allergen species; enables the physician to distinguish between
therefore sometimes it is not clear what positivity from cross-reactions and true
the disease-eliciting source is. This applies venom allergy before selecting the right
to pollen allergies as well as to animal, immunotherapeutic solution. Api m 3 and
dust mite and venom allergy. Tests with Api m 10 can be absent or underrepresented
molecular allergens can help streamline the in VIT extracts and venom AIT in patients
identification process1-6. Specific molecules sensitized to these components may be less
from, for example, grass can differentiate and efficient10-11.
identify true grass-allergic patients.
References
Determining a patient’s molecular profile 1. Matricardi PM et al. EAACI Molecular Allergology User’s Guide.
will also help to indicate if they are likely to European Society of Pediatric Allergy and Immunology. 2016;27
respond satisfactorily to immunotherapy3, Suppl 23:1-250.
6-7
. Immunotherapy products vary from 2. Kleine-Tebbe J and Jakob T Editors: Molecular Allergy
manufacturer to manufacturer; they contain
molecules from the allergen source. But 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
which ones and in what quantity? Most 10.1007/978-3-319-42499-6
products contain larger quantities of the 3. Canonica GW et al. A WAO - ARIA - GA²LEN consensus
major allergens such as Bet v 1 in birch or Phl Organ J. 2013 Oct 3;6(1):17.
p 1 and Phl p 5 in timothy grass and Der p 1 4. Focke M et al. Heterogeneity of commercial timothy grass pollen
in mite extracts, while sometimes much lower extracts. Clin Exp Allergy 2008;38(8):1400-1408.
quantities of other allergens are included7. 5. Asero R. Component-resolved diagnosis-assisted prescription

of allergen-specific immunotherapy: a practical guide Eur Ann
Patients who are positive only to the minor Allergy Clin Immunol. 2012;44(5):183-7.
allergens are therefore less likely to respond 6. Schmid-Grendelmeier P. Recombinant Allergens – Routine
satisfactorily1-7,10-11. diagnostics or still only science? Der Hautarzt 2010;61(11):946-
953.
7. Focke M et al. Molecular composition and biological activity
36
of commercial birch pollen allergen extracts. Eur J Clin Invest
2009;39(5):429-436.
8. Mittermann I et al. Recombinant allergen-based IgE testing
to distinguish bee and wasp allergy. J Allergy Clin Immunol
2010;125(6):1300-1307.
9. Muller U et al. IgE to recombinant allergens Api m 1, Ves v 1 and
Ves v 5 distinguish double sensitization from cross-reaction in
venom allergy. Allergy 2012;67:1069-1073.
10. Grunwald T et al., Molecular cloning and expression in insect
cells of honeybee venom allergen acid phosphatase (Api m 3). J
Allergy Clin Immunol 2006; 117:848-54.
11. Blank S et al., Api m 10, a genuine A. mellifera venom allergen,
is clinically relevant but underrepresented in therapeutic
extracts. Allergy 2011; 66:1322-1329.
Common questions
regarding allergen
components
What is a molecular allergen-specific IgE Generally speaking they don’t. For example,
test and does it differ technically from there are over 30 proteins reported in the
normal specific IgE tests that I request peanut extract, many not clinically relevant
from my laboratory? or with unknown relevance. The field of
Technically they work in the same way and molecular allergology is ever-expanding as
give results in kUA /L, the same as normal we gain further scientific information and
whole extract sources such as cat, peanut knowledge. Thermo Fisher Scientific
etc. supplies (Phadia AB is manufacturer)
between 2-4 new components every year.
How many ImmunoCAP Allergen Since all components are not available
Components are available? as single tests it is suggested to use the
There are currently over 100 tests with available components together with the
allergen components in the product range. whole extract to cover the spectrum of
A list is included in this guide, however patients’ sensitizations.
availability may differ between countries.
What is ImmunoCAP ISAC?
For each allergen source how do I ImmunoCAP ISAC is a microarray chip which
know that the ImmunoCAP Allergen tests for IgE to 112 allergen components
Components represent the whole simultaneously. It is a multiplex test giving
allergen extract? semi-quantitative results on a patient’s
37
allergen component sensitization profile. It
has been found useful for the diagnosis of
the following, but this list is not exhaustive:
complex allergy, OAS, and cases of multi-
sensitization, idiopathic anaphylaxis and
high total IgE patients. More information
on ImmunoCAP ISAC is available in Go
Molecular, Book 2.
Where can I get access to ImmunoCAP

ISAC?
Your local immunology laboratory may have
ImmunoCAP ISAC in-house, otherwise the
lab should be able to refer your sample for
testing. Therefore contact your local lab to
find out what is possible.
Is it possible to have an ImmunoCAP

Whole Allergen test result that is
negative and an ImmunoCAP Allergen
Component test result that is positive
(from the same source)?
This is possible in some cases. The
whole allergen contains a mix of proteins,
representing the natural composition at the
source, while the allergen component is one
single pure protein. Overall the component
tests give higher specificity and sometimes
even more sensitivity. Using a combination of
both whole extract and components (where
possible) is currently considered the best
strategy for diagnosis.
38
Glossary
Allergen component – single immunogenic Bet v 1 from birch or Ara h 2 from peanut.
protein from an allergen source e.g. Ara h 2
from peanut. Minor and major allergens – Major allergen
components are those to which at least 50%
Cross-reactivity/Cross-sensitization – IgE of relevant patients are sensitized. Minor
antibodies directed against one allergen may allergens are often less prevalent in triggering
cross-react to structurally related allergens allergy. For instance, in birch allergy the major
from other allergen sources. Cross-reactive allergen is Bet v 1 (PR-10), whilst a minor
antibodies can cause a variety of different allergen is Bet v 2 (profilin).
clinical outcomes.
Secondary sensitization – IgE antibodies
Epitope – Defined substructure of a protein directed to a primary sensitizer cross-react
to which an antibody binds. due to the similarity of the proteins/allergens
and give rise to cross-reactive sensitization.
ImmunoCAP – an in vitro test for the This occurs in food-pollen syndrome for
measurement of specific IgE antibodies. example, when an individual is sensitized to
ImmunoCAP is one of the market leaders and birch PR-10 (Bet v1) and the IgE antibodies
has been established for several decades. then cross-react to peanut PR-10 (Ara h 8).
ImmunoCAP is also available for testing for
other immunoglobulins (e.g. IgG4/ IgG). Allergen extract – refers to the crude
mixture of proteins that is obtained by
Pan-allergen – evolutionarily conserved extraction of an allergen source (e.g. birch
and widely distributed allergen, ubiquitous pollen or peanut).
component of several sources of allergens.
IgE antibodies to a pan-allergen may cross-
react with homologous allergens and thus
also give rise to symptoms to many different
allergens in a patient.
Primary sensitizing allergen – an allergen

originally triggering the immune system to
produce specific IgE antibodies. For example
39
Educational resources
allergyai.com – Home Page of
Immunodiagnostics, Thermo Fisher Scientific
allergen.org – International Union for

Immunological Sciences/WHO Allergen
Database
Matricardi PM et al. EAACI Molecular

Allergology User’s Guide. Pediatric allergy
and immunology: official publication of the
European Society of Pediatric Allergy and
Immunology. 2016;27 Suppl 23:1-250.
Kleine-Tebbe J and Jakob T Editors:

Molecular Allergy Diagnostics. Innovation
for a Better Patient Management. Springer
International Publishing Switzerland 2017.
ISBN 978-3-319-42498-9 ISBN 978-3-319-
42499-6 (eBook), DOI 10.1007/978-3-319-
42499-6
Canonica GW et al. A WAO – ARIA –

GA2LEN consensus document on molecular-
based allergy diagnostics. World Allergy
Organ J 2013;6(1):17.

40
Using ImmunoCAP
Allergen Component tests
The term ‘ImmunoCAP Allergen Component’ ImmunoCAP Allergen Components,
is used for singleplex ImmunoCAP products singleplex as well as multiplex, are useful
based on molecular allergens purified tools for the physician when investigating
from either their natural source (native) or and explaining allergic reactions in more
biotechnologically produced as recombinant detail and to determine if cross-reacting IgE
proteins bound to the conventional antibodies or primary sensitization causes
ImmunoCAP solid phase. them. However as all test results they must
be evaluated by the physician together with
By using tests for single allergen components the clinical history of the individual patient.
as a complement to more traditional specific
IgE antibody tests, further clinically relevant Presence of allergen specific IgE implies
and quantitative information can be gained as a risk of allergic disease and generally the
an aid to the physician in making a diagnosis higher the level of IgE antibodies the higher
of allergy. the probability of a clinically manifest allergic
reaction1-5. However, due to differences in
Allergen components are also available in individual patient sensitivities identical results
a multiplex microarray format, ImmunoCAP for the same allergens may not be associated
ISAC. Here each test contains 112 with clinically equivalent manifestations. This
components giving 112 semi-quantitative may also be true for one individual patient
specific IgE results, thus presenting at different occasions due to presence or
a snapshot of the patient’s complete absence of reaction promoting cofactors1-5.
sensitization profile in one test.
Absence of detectable allergen specific IgE
More information on ImmunoCAP ISAC is antibodies does not necessarily exclude the
available in Book 2. potential for an allergy-like reaction1,2.
The interpretation of sensitizations to allergen Limitations of ImmunoCAP products test

components that is described in this book, results:
(as well as in book 2) is the same for both Samples with results below limit of
single and multiplex formats. quantitation obtained with ImmunoCAP
Allergen Components are recommended
41
to be tested with the corresponding 5. Van Hage M et.al. ImmunoCAP assays: Pros and cons in
extract based ImmunoCAP Allergen and/
or additional relevant ImmunoCAP Allergen
Components, if not already performed
and a clinical indication is present. The
extract based testing can cover additional
allergen components present in the allergen
source material to which the patient
may be sensitized, but which are not
presently available as ImmunoCAP Allergen
Components or in ImmunoCAP ISAC.
A result below limit of quantitation obtained

with an extract based ImmunoCAP Allergen
never excludes the possibility of obtaining
measurable concentrations of specific IgE
when testing with ImmunoCAP Allergen
Components from the same allergen source.
This is due to the fact that some components
may be present in very low amounts in the
natural extract.
References
Suppl 23:1-250.
978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook), DOI
10.1007/978-3-319-42499-6.
Organ J. 2013 Oct 3;6(1):17.
4. Wickman M. When allergies complicate allergies. Allergy
2005;60(S79):14-18.
Disclaimer:
The content of this book is intended as an aid to the physician to interpret allergen specific IgE antibody test results.
It is not intended as medical advice on an individual level. A definitive clinical diagnosis of IgE mediated allergic disorders
should only be made by the physician based on the clinical history for the individual patient, after all clinical and laboratory
findings have been evaluated. It should not be based on the results of any single diagnostic method.
42
ImmunoCAP Allergen
Component list*
Product description Latin name Code Size Art. no. Barcode
Grass pollen
Cyn d 1 Bermuda grass Cynodon dactylon g216 10 14-4972-01 CFA
rPhl p 1 Timothy Phleum pratense g205 10 14-5234-01 BSU
rPhl p 2 Timothy Phleum pratense g206 10 14-5235-01 C0K
nPhl p 4 Timothy Phleum pratense g208 10 14-5288-01 C0L
rPhl p 5b Timothy Phleum pratense g215 10 14-5338-01 BV3
rPhl p 6 Timothy Phleum pratense g209 10 14-5289-01 BSV
rPhl p 7 Timothy Phleum pratense g210 10 14-5290-01 BSW
rPhl p 11 Timothy Phleum pratense g211 10 14-5291-01 BSX
rPhl p 12 Profilin, Timothy Phleum pratense g212 10 14-5292-01 BSY
rPhl p 1, rPhl p 5b Timothy Phleum pratense g213 10 14-5312-01 BU1
rPhl p 7, rPhl p 12 Timothy Phleum pratense g214 10 14-5313-01 BU2
Weed pollen
nAmb a 1 Ragweed Ambrosia artemisiifolia (A. elatior) w230 10 14-4969-01 CF8
nArt v 1 Mugwort Artemisia vulgaris w231 10 14-4970-01 CF9
nArt v 3 LTP, Mugwort Artemisia vulgaris w233 10 14-4983-01 CJ2
rPar j 2 LPT, Wall pellitory Parietaria judaica w211 10 14-5311-01 C2M
rPla l 1 Plantain Plantago lanceolata w234 10 14-5751-01 D1H
nSal k 1 Saltwort Salsola kali w232 10 14-4978-01 CFE
Tree pollen
rBet v 1 PR-10, Birch Betula verrucosa t215 10 14-5225-01 BPV
rBet v 2 Profilin, Birch Betula verrucosa t216 10 14-5226-01 BR1
rBet v 4 Birch Betula verrucosa t220 10 14-5287-01 BT7
rBet v 6 Birch Betula verrucosa t225 10 14-5345-01 CF1
rBet v 2, rBet v 4 Birch Betula verrucosa t221 10 14-5310-01 BU0
nCup a 1 Cypress Cupressus arizonica t226 10 14-4977-01 CFD
rOle e 1 Olive Olea europaea t224 10 14-5705-01 CTC
nOle e 7 LTP, Olive Olea europeae t227 10 14-4993-01 CKT
rOle e 9, Olive Olea europeae t240 10 14-4999-01 CTZ
rPla a 1 Maple leaf sycamore, London plane Platanus acerifolia t241 10 14-5957-01 D2H
*Not all ImmunoCAP Products are available in all regions/ countries
43
Microorganisms
rAlt a 1 Alternaria alternata m229 10 14-5346-01 CE0
rAsp f 1 Aspergillus fumigatus m218 10 14-5293-01 BPL
rAsp f 2 Aspergillus fumigatus m219 10 14-5294-01 BPM
rAsp f 3 Aspergillus fumigatus m220 10 14-5295-01 BT4
rAsp f 4 Aspergillus fumigatus m221 10 14-5296-01 BPN
rAsp f 6 Aspergillus fumigatus m222 10 14-5297-01 BPP
Epidermals and animal proteins

nBos d 6 BSA, Cow Bos spp. e204 10 14-5009-01 BRV
rCan f 1 Dog Canis familiaris e101 10 14-4955-01 CBN
rCan f 2 Dog Canis familiaris e102 10 14-4956-01 CBP
nCan f 3 Dog serum albumin Canis familiaris e221 10 14-5241-01 C14
rCan f 4 Dog Canis familiaris e229 10 14-5755-01 CZY
rCan f 5 Dog Canis familiaris e226 10 14-4998-01 CMZ
rCan f 6 Dog Canis familiaris e230 10 14-6081-01 E2X
rFel d 1 Cat Felis domesticus e94 10 14-4905-01 BY0
rFel d 2 Cat serum albumin Felis domesticus e220 10 14-5240-01 BRX
rFel d 4 Cat Felis domesticus e228 10 14-5702-01 CT9
rFel d 7 Cat Felis domesticus e231 10 14-6082-01 E2Y
rEqu c 1 Horse Equus caballus e227 10 14-5700-01 CN7
nSus s Pig serum albumin, Swine Sus scrofa e222 10 14-5242-01 C36
Mites
rDer p 1 House dust mite Dermatophagoides Pteronyssinus d202 10 14-5996-01 DP4
rDer p 2 House dust mite Dermatophagoides Pteronyssinus d203 10 14-4967-01 CG2
rDer p 10 Tropomyosin, House dust mite Dermatophagoides Pteronyssinus d205 10 14-4985-01 CG5
rDer p 23 House dust mite Dermatophagoides Pteronyssinus d209 10 14-6040-01 DWU
Venoms
rApi m 1 Phospholipase A2, Honey bee Apis mellifera i208 10 14-4987-01 CJ7
rApi m 2 Hyaluronidase, Honey bee Apis mellifera i214 10 14-6014-01 DUD
rApi m 3, Acid phosphatase, Honey bee Apis mellifera i215 10 14-6015-01 DUC
rApi m 5 Dipeptidyl peptidase, Honey bee Apis mellifera i216 10 14-6016-01 DUB
rApi m 10 Icarapin, Honey bee Apis mellifera i217 10 14-6004-01 DR0
rVes v 1 Phospholipase A1, Common wasp Vespula vulgaris i211 10 14-4995-01 CMR
rVes v 5 Common wasp Vespula vulgaris i209 10 14-4992-01 CJ8
rPol d 5 Paper wasp Polistes dominulus i210 10 14-4994-01 CJ9
Occupational
rHev b 1 Latex Hevea brasiliensis k215 10 14-5324-01 C20
rHev b 3 Latex Hevea brasiliensis k217 10 14-5326-01 C2A
rHev b 5 Latex Hevea brasiliensis k218 10 14-5327-01 C1Z
rHev b 6.02 Latex Hevea brasiliensis k220 10 14-5329-01 C22
rHev b 8 Profilin, Latex Hevea brasiliensis k221 10 14-5330-01 C1V
rHev b 11 Latex Hevea brasiliensis k224 10 14-5333-01 C29
44
ImmunoCAP Allergen Component list continued*

Occupational / Enzymes
Alkalase Alkalase k205 10 14-5126-01 C1F
nAna c 2 Bromelain, Pineapple nAna c 2 Bromelain, Pineapple k202 10 14-5127-01 BT1
nAsp o 21 alpha-amylase nAsp o 21 alpha-amylase k87 10 14-4370-01 595
nCar p 1 Papain, Papaya nCar p 1 Papain, Papaya k201 10 14-5130-01 BT0
nGal d 4 Lysozyme, Egg nGal d 4 Lysozyme, Egg k208 10 14-5128-01 C0T
Maxatase Maxatase k204 10 14-5129-01 C2F
Savinase Savinase k206 10 14-5132-01 C2R
nSus s Pepsin, Swine nSus s Pepsin, Swine k213 10 14-5258-01 C3B
Foods
rAct d 8 PR-10, Kiwi Actinidia deliciosa f430 10 14-4984-01 CG7
rAna o 3 Cashew nut Anacardium occidentale f443 10 14-5760-01 D0W
rApi g 1.01 PR-10, Celery Apium graveolens f417 10 14-4957-01 CBR
rAra h 1 Peanut Arachis hypogaea f422 10 14-4963-01 CDF
rAra h 2 Peanut Arachis hypogaea f423 10 14-4964-01 CDG
rAra h 3 Peanut Arachis hypogaea f424 10 14-4965-01 CDH
rAra h 6 Peanut Arachis hypogaea f447 10 14-6041-01 DYU
rAra h 8 PR-10, Peanut Arachis hypogaea f352 10 14-5341-01 CEZ
rAra h 9 LTP, Peanut Arachis hypogaea f427 10 14-4980-01 CFC
rBer e 1 Brazil nut Bertholletia excelsa f354 10 14-5343-01 CDS
rSes i 1, Sesame seed Sesamum indicum f449 10 14-6109-01 E7M
nBos d 4 alpha-lactalbumin, Milk Bos spp. f76 10 14-4522-01 CTP
nBos d 5 beta-lactoglobulin, Milk Bos spp. f77 10 14-4523-01 CTR
nBos d 8 Casein, Milk Bos spp. f78 10 14-4524-01 CTS
rCor a 1 PR-10, Hazel nut Corylus avellana f428 10 14-4981-01 CFB
rCor a 8 LTP, Hazel nut Corylus avellana f425 10 14-4968-01 CDP
nCor a 9, Hazel nut Corylus avellana f440 10 14-5758-01 D0M
rCor a 14, Hazel nut Corylus avellana f439 10 14-5754-01 CZP
rCyp c 1 Carp Cyprinus carpio f355 10 14-5344-01 CF0
rGad c 1 Cod Gadus morhua f426 10 14-4971-01 CEY
nGal d 1 Ovomucoid, Egg Gallus spp. f233 10 14-4805-01 904
nGal d 2 Ovalbumin, Egg Gallus spp. f232 10 14-4804-01 903
nGal d 3 Conalbumin, Egg Gallus spp. f323 10 14-5222-01 C18
rGly m 4 PR-10, Soy Glycine max f353 10 14-5340-01 CDR
nGly m 5 beta-conglycinin, Soy Glycine max f431 10 14-4990-01 CLV
nGly m 6 Glycinin Glycine max f432 10 14-4991-01 CLU
rJug r 1 Walnut Juglans regia f441 10 14-5762-01 D0T
rJug r 3 LTP, Walnut Juglans regia f442 10 14-5954-01 D11
rMal d 1 PR-10, Apple Malus domestica f434 10 14-5703-01 CWR
rMal d 3 LTP, Apple Malus domestica f435 10 14-5704-01 CWS
rPen a 1 Tropomyosin, Shrimp Penaeus aztecus f351 10 14-5335-01 C11
rPru p 1 PR-10, Peach Prunus persica f419 10 14-4960-01 CBV
*Not all ImmunoCAP Products are available in all regions/ countries
45
Foods continued
rPru p 3 LTP, Peach Prunus persica f420 10 14-4961-01 CBW
rPru p 4 Profilin, Peach Prunus persica f421 10 14-4962-01 CBX
rPru p 7, Peach Prunus persica f454 10 14-6086-01 E3Z
rTri a 14 LTP, Wheat Triticum aestivum f433 10 14-5701-01 CN6
rTri a 19 Omega-5 Gliadin, Wheat Triticum aestivum f416 10 14-4954-01 C8H
Gliadin f98 10 14-5752-01 CXG
Miscellaneous
nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, o215 10 14-5997-01 DPC
bovine
MUXF3 CCD, Bromelain o214 10 14-5339-01 CJU
46
ImmunoCAP ISAC112i
Chip Allergen
Components
Allergen Allergen source Latin name Protein group
component common name
Food allergens
Gal d 1 Egg white Gallus domesticus Ovomucoid
Gal d 2 Egg white Gallus domesticus Ovalbumin
Gal d 3 Egg white Gallus domesticus Conalbumin/Ovotransferrin
Gal d 5 Egg yolk/chicken meat Gallus domesticus Livetin/Serum albumin
Bos d 4 Cow’s milk Bos domesticus Alpha-lactalbumin
Bos d 5 Cow’s milk Bos domesticus Beta-lactoglobulin
Bos d 6 Cow’s milk and meat Bos domesticus Serum albumin
Bos d 8 Cow’s milk Bos domesticus Casein
Bos d lactoferrin Cow’s milk Bos domesticus Transferrin
Gad c 1 Cod Gadus callarias Parvalbumin
Pen m 1 Shrimp Penaeus monodon Tropomyosin
Pen m 2 Shrimp Penaeus monodon Arginine kinase
Pen m 4 Shrimp Penaeus monodon Sarcoplasmic Ca-binding protein
Ana o 2 Cashew nut Anacardium occidentale Storage protein, 11S globulin
Ana 0 3 Cashew nut Anacardium occidentale Storage Protein, 2S albumin
Ber e 1 Brazil nut Bertholletia excelsa Storage protein, 2S albumin
Cor a 1.0401 Hazelnut Corylus avellana PR-10 protein
Cor a 8 Hazelnut Corylus avellana Lipid transfer protein (nsLTP)
Cor a 9 Hazelnut Corylus avellana Storage protein, 11S globulin
Cor a 14 Hazelnut Corylus avellana Storage Protein, 2S albumin
Jug r 1 Walnut Juglans regia Storage protein, 2S albumin
Jug r 3 Walnut Juglans regia Lipid transfer protein (nsLTP)
Ses i 1 Sesame seed Sesamum indicum Storage protein, 2S albumin
Ara h 1 Peanut Arachis hypogaea Storage protein ,7S globulin
Ara h 2 Peanut Arachis hypogaea Storage protein, 2S albumin
Ara h 3 Peanut Arachis hypogaea Storage protein, 11S globulin
Ara h 6 Peanut Arachis hypogaea Storage protein, 2S albumin
Ara h 8 Peanut Arachis hypogaea PR-10 protein
Ara h 9 Peanut Arachis hypogaea Lipid transfer protein (nsLTP)
Gly m 4 Soybean Glycine max PR-10 protein
Gly m 5 Soybean Glycine max Storage protein, Beta-conglycinin
Gly m 6 Soybean Glycine max Storage protein, Glycinin
Fag e 2 Buckwheat Fagopyrum esculentum Storage protein, 2S albumin
Tri a 14 Wheat Triticum aestivum Lipid transfer protein (nsLTP)
Tri a 19.0101 Wheat Triticum aestivum Omega-5 gliadin
Tri a aA_TI Wheat Triticum aestivum
Act d 1 Kiwi Actinidia deliciosa
Act d 2 Kiwi Actinidia deliciosa Thaumatine-like protein
Act d 5 Kiwi Actinidia deliciosa
Act d 8 Kiwi Actinidia deliciosa PR-10 protein
Api g 1 Celery Apium graveolens PR-10 protein
Mal d 1 Apple Malus domestica PR-10 protein
Pru p 1 Peach Prunus persica PR-10 protein
Pru p 3 Peach Prunus persica Lipid transfer protein (nsLTP)
47
Aeroallergens
Cyn d 1 Bermuda grass Cynodon dactylon Grass group 1
Phl p 1 Timothy grass Phleum pratense Grass group 1
Phl p 4 Timothy grass Phleum pratense
Phl p 7 Timothy grass Phleum pratense Polcalcin
Phl p 12 Timothy grass Phleum pratense Profilin
Aln g 1 Alder Alnus glutinosa PR-10 protein
Bet v 1 Birch Betula verrucosa PR-10 protein
Bet v 2 Birch Betula verrucosa Profilin
Bet v 4 Birch Betula verrucosa Polcalcin
Cor a 1.0101 Hazel pollen Corylus avellana PR-10 protein
Cry j 1 Japanese ceder Cryptomeria japonica
Cup a 1 Cypress Cupressus arizonica
Ole e 1 Olive Olea europaea
Ole e 7 Olive Olea europaea Lipid transfer protein (nsLTP)
Ole e 9 Olive Olea europaea
Pla a 1 Plane tree Platanus acerifolia
Pla a 3 Plane tree Platanus acerifolia Lipid transfer protein (nsLTP)
Amb a 1 Ragweed Ambrosia artemisiifolia
Art v 1 Mugwort Artemisia vulgaris
Art v 3 Mugwort Artemisia vulgaris Lipid transfer protein (nsLTP)
Che a 1 Goosefoot Chenopodium album
Mer a 1 Annual mercury Mercurialis annua Profilin
Par j 2 Wall pellitory Parietaria judaica Lipid transfer protein (nsLTP)
Pla l 1 Plantain (English) Plantago lanceolata
Sal k 1 Saltwort Salsola kali
Can f 1 Dog Canis familiaris Lipocalin
Can f 3 Dog Canis familiaris Serum albumin
Can f 5 Dog Canis familiaris Arginine esterase
Equ c 1 Horse Equus caballus Lipocalin
Equ c 3 Horse Equus caballus Serum albumin
Fel d 1 Cat Felis domesticus Uteroglobin
Fel d 2 Cat Felis domesticus Serum albumin
Fel d 4 Cat Felis domesticus Lipocalin
Mus m 1 Mouse Mus musculus Lipocalin
Alt a 1 Alternaria Alternaria alternata
Alt a 6 Alternaria Alternaria alternata Enolase
Asp f 1 Aspergillus Aspergillus fumigatus
Asp f 3 Aspergillus Aspergillus fumigatus
Asp f 6 Aspergillus Aspergillus fumigatus Mn superoxide dismutase
Cla h 8 Cladosporium Cladosporium herbarum
Blo t 5 House dust mite Blomia tropicalis
Der f 1 House dust mite Dermatophagoides farinae
Der f 2 House dust mite Dermatophagoides farinae
Der p 1 House dust mite Dermatophagoides pteronyssinus
Der p 2 House dust mite Dermatophagoides pteronyssinus
Der p 10 House dust mite Dermatophagoides pteronyssinus Tropomyosin
Der p 23 House dust mite Dermatophagoides pteronyssinus Peritrophin-like protein
Lep d 2 Storage mite Lepidoglyphus destructor
48 Aeroallergens continued overleaf...

Aeroallergens continued
Bla g 1 Cockroach Blattella germanica
Bla g 7 Cockroach Blattella germanica Tropomyosin
Other
Ani s 1 Anisakis Anisakis simplex
Ani s 3 Anisakis Anisakis simplex Tropomyosin
Hev b 1 Latex Hevea brasiliensis
Hev b 6.01 Latex Hevea brasiliensis
Hev b 8 Latex Hevea brasiliensis Profilin
Gal-alpha-1,3-Gal Alpha gal Thryoglobulin
MUXF3 Sugar epitope from Bromelain CCD-marker
49
Notes
50
Notes
51
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75163.AL.GB1.EN.v1.19

Go Molecular!: A Clinical Reference Guide To Molecular Allergy

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Go Molecular!: A Clinical Reference Guide To Molecular Allergy

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2021

Revised and updated 2nd edition (2021)

172050.AL.EU, INT, JP1.EN.v1.21

Introduction: Molecular allergens tell us more 5

Allergen component nomenclature 9

Specific and cross-reactive allergens 10

Other clinical considerations 11

Interpreting results from cross-reactive protein families 19

Summary of plant food components 21

Plant allergen components in some common foods 24

Other allergen components 26

Immunotherapeutics – Aeroallergens and venoms 36

Common questions regarding molecular components 37

Using ImmunoCAP Allergen Component tests 41

ImmunoCAP Allergen Component list 43

ImmunoCAP ISAC112i Chip Allergen Components 47

While traditional extract-based IgE blood

Molecular diagnostics reveals more factual

Ara h 2 is the most allergenic protein in

Other specific IgE antibodies are directed

*ImmunoCAP Allergen f423, Allergen component rAra h 2 Peanut

IgE test results of a patient with suspect plant food allergy

Bet v 1 (Birch PR-10) 42.9 kUA/L

However for different patients identical results

Allergen components are given a name

Peanut – Arachis hypogaea – Ara h 2

Figure 3: Illustration of a typical allergen test profile

Cat Dog Horse Birch Grass Weed Mite Mould

Egg Fish Milk Hazelnut Peanut Soy Wheat

This website contains an educational course

Other clinical considerations

Stable proteins can caused

Figure 4: An overview of the biological

Molecules of high allergenic potential mouth, causing less problematic reactions

When sensitization to cross-reactive allergens

Bet v 1 (Birch PR-10) 42.9 kUA/L

Clinical interpretation: Clinical interpretation:

Ara h 1 (Storage protein) 20.8 kUA/L

Bet v 1 (Birch PR-10) 42.9 kUA/L

Summary of plant food

The majority of food allergen components in

Table References 5. Treudler R. and Simon JC. Overview of component

Profilin PR-10 Storage

An overview of the biological differences in how allergen proteins

Component family Profilin PR-10 LTP 2S Vicilin- Legumin- Other

Sunflower seed Hel a 2 Hel a 3 Hel a 2 S

Normal WHO/IUIS listed Italic Described in peer reviewed literature

Likely but not yet described

Component family Profilin PR-10 LTP 2S Vicilin- Legumin- Other

Plants often driving sensitization

References 4. Sastre J. Molecular diagnosis in allergy. Clin Exp

children don’t outgrow their egg allergy until

Fel d 1 Fel d 4 Fel d 7 Fel d 2 Fel df 14

Cat Dog Horse

Specific components in squares

Uteroglobin Lipocalin family Kallikrein Serum albumins

Protein family Summary Clinical Importance

Uteroglobin Uteroglobin, a steroid-inducible High. Fel d 1 the major cat allergen

Europe 1-3,5. Group 1 and group 5 allergens

References 4. Sastre J. Molecular diagnosis in allergy. Clin Exp