SYSTEM

E
Anti-TPO
2K47
840242/R2

Anti-TPO
Customer Service
United States: 1-877-4ABBOTT
International: Call your Abbott Representative

This package insert must be read carefully prior to use. Package insert instructions must be followed accordingly.
Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package
insert.

© 2005 Abbott Laboratories / ARCHITECT Anti-TPO

July 2005

Key to symbols used

List Number Lot Number

For In Vitro Diagnostic Use Expiration Date

Store at 2-8°C Reaction Vessels

Sample Cups

Consult instructions for use Septum

Replacement Caps
Serial Number
Produced by
Fisher Scientific, 8365 Valley Pike,
Reagent Lot
Middletown, VA 22645, USA Authorized Representative
for Abbott Laboratories,
Abbott Park, IL 60064, USA Assay CD-ROM
Legal Manufacturer
ABBOTT Control Number
Max-Planck-Ring 2
65205 Wiesbaden
Germany
+49-6122-580 See REAGENTS section for a full explanation of symbols used in reagent component naming.

ABBOTT
Diagnostics Division
1
NAME Other Reagents
ARCHITECT® Anti-TPO ARCHITECT i Pre-Trigger Solution

INTENDED USE • Pre-Trigger Solution containing 1.32%

ARCHITECT Anti-TPO is a Chemiluminescent Microparticle Immunoassay (w/v) hydrogen peroxide.
(CMIA) for the quantitative determination of the IgG class of thyroid peroxidase ARCHITECT i Trigger Solution
autoantibodies (anti-TPO) in human serum and plasma on the ARCHITECT i
System. The ARCHITECT Anti-TPO assay is intended for use as an aid in • Trigger Solution containing 0.35N sodium
the diagnosis of thyroid disease. hydroxide.
ARCHITECT i Wash Buffer
SUMMARY AND EXPLANATION OF TEST
It was first demonstrated by Trotter et al. in 19571 and subsequently by Roitt • Wash Buffer containing phosphate buffered saline
and Doniach in 19582 that many patients with Hashimoto’s thyroiditis had solution. Preservative: antimicrobial agent.
detectable autoantibodies in their blood directed at a thyroid antigen distinct WARNINGS AND PRECAUTIONS
from thyroglobulin. This antigen was termed thyroid microsomal and it has
since been demonstrated that most if not all anti-thyroid microsomal For In Vitro Diagnostic Use.
autoantibodies recognize thyroid peroxidase (TPO).3 Safety Precautions
TPO is a membrane-bound glycoprotein enzyme with an approximate mass
of 107kD. The in vivo function is the iodination of tyrosine in the synthesis
• CAUTION: This product requires the handling of human specimens.
of T3 and T4.4 Autoimmune reactivity to TPO is believed to be polyclonal and
It is recommended that all human sourced materials be considered
heterogeneous in nature with a minimum of six antigenic determinants being
potentially infectious and handled in accordance with the OSHA Standard
recognized, comprising both conformational and linear epitopes.5,6 In
on Bloodborne Pathogens.24 Biosafety Level 225 or other appropriate
addition, the proportion of each immunoglobulin class (G or M) or subclass
biosafety practices 26,27 should be used for materials that contain or are
(G1 – G4) as well as their affinity varies widely from patient to patient.7,8
suspected of containing infectious agents.
Unlike autoantibodies to thyroglobulin (anti-Tg), autoantibodies to TPO fix
complement,9 are potentially deleterious and may have a pathogenic role in • Microparticles contain Potassium Ferricyanide and are classified per
(destructive) autoimmune thyroid disease.10,11 Anti-TPO antibodies are found applicable European Community (EC) Directives as: Harmful (Xn). The
often in conjunction with anti-Tg in the majority of cases of Hashimoto’s following are the appropriate Risk (R) and Safety (S) phrases.
thyroiditis, Primary Myxedema, and Graves’ disease. The relationship of R32 Contact with acids liberates very toxic gas.
autoimmune thyroid disease to pregnancy has been the subject of S35 This material and its container must be disposed of in
considerable interest with the recognition of the postpartum thyroid disease a safe way.
syndromes.12 Anti-TPO antibodies are demonstrable in most cases of S36 Wear suitable protective clothing.
S46 If swallowed, seek medical advice immediately and
postpartum thyroiditis and it has been found that the presence of autoantibody
show this container or label.
in early pregnancy was associated with a high risk of asymptomatic
• The ARCHITECT i Trigger Solution contains sodium hydroxide (NaOH)
postpartum hypothyroidism.13-17
and is classified per applicable European Community (EC) Directives
It is common to find anti-TPO antibodies in the absence of autoantibodies to
as: Irritant (Xi). The following are the appropriate Risk (R) and Safety (S)
thyroglobulin, particularly in patients with small goitres and up to 64% of
phrases.
cases of autoimmune hypothyroidism have been reported to be associated
with anti-TPO antibodies alone. 18 In addition, anti-TPO antibodies are R41 Risk of serious damage to eyes.
S25 Avoid contact with eyes.
frequently found in patients with other autoimmune diseases such as
S26 In case of contact with eyes, rinse immediately with
Rheumatoid Arthritis, Addison’s Disease and Type I Diabetes.19-21 They are
plenty of water and seek medical advice.
also detectable at low levels in up to 20% of asymptomatic individuals,22 S35 This material and its container must be disposed of in
particularly the elderly23 and more often in women than in men, although the a safe way.
clinical significance of these autoantibodies is unclear. S36/39 Wear suitable protective clothing and eye/face
protection.
BIOLOGICAL PRINCIPLES OF THE PROCEDURE S46 If swallowed, seek medical advice immediately
The ARCHITECT Anti-TPO assay is a two-step immunoassay for the and show this container or label.
quantitative determination of anti-TPO in human serum and plasma using • For product not classified as dangerous per European Directive 1999/45/
CMIA technology with flexible assay protocols, referred to as Chemiflex®. EC - Safety data sheet available for professional user on request.
In the first step, sample, assay diluent and TPO coated paramagnetic
microparticles are combined and incubated. Anti-TPO present in the sample Handling Precautions
binds to the TPO coated microparticles. After washing, anti-human IgG • Do not use reagent kits beyond the expiration date.
acridinium labeled conjugate is added in the second step. Following another • Do not pool reagents within a kit or between reagent kits.
incubation and wash, pre-trigger and trigger solutions are added to the • Prior to loading the ARCHITECT Anti-TPO Reagent Kit on the system
reaction mixture. The resulting chemiluminescent reaction is measured as for the first time, the microparticle bottle requires mixing to resuspend
relative light units (RLUs). A direct relationship exists between the amount of microparticles that have settled during shipment. For microparticle mixing
anti-TPO in the sample and the RLUs detected by the ARCHITECT i* system instructions, refer to the PROCEDURE, Assay Procedure section of
optics. For additional information on system and assay technology, refer to this package insert.
the ARCHITECT System Operations Manual, Section 3. • Septa MUST be used to prevent reagent evaporation and
*i = immunoassay contamination and to ensure reagent integrity. Reliability of assay
results cannot be guaranteed if septa are not used according to the
REAGENTS instructions in this package insert.
Reagent Kit, 100 Tests • To avoid contamination, wear clean gloves when placing a septum
NOTE: Some kit sizes are not available in all countries; please contact your on an uncapped reagent bottle.
local distributor. • Prior to placing the septum on an uncapped reagent bottle, squeeze the
ARCHITECT Anti-TPO Reagent Kit (2K47) septum in half to confirm that the slits are open. If the slits appear sealed,
continue to gently squeeze the septum to open the slits.
• 1 or 4 Bottles (6.6 mL) Thyroid peroxidase • Once a septum has been placed on an open reagent bottle, do not
(recombinant) coated microparticles in MES buffer with protein (bovine) invert the bottle as this will result in reagent leakage and may
stabilizer. Preservative: antimicrobial agents. compromise assay results.
• 1 or 4 Bottles (5.9 mL) Anti-human IgG (mouse, • Over time, residual liquids may dry on the septum surface. These are
monoclonal) acridinium labeled conjugate in MES buffer with protein typically dried salts which have no effect on assay efficacy.
(bovine) stabilizer. Preservative: antimicrobial agents. • For a detailed discussion of handling precautions during system operation,
• 1 or 4 Bottles (10.0 mL) Assay Diluent in MES buffer. refer to the ARCHITECT System Operations Manual, Section 7.
Preservative: antimicrobial agents.

2
Storage Instructions Preparation for Analysis
• The ARCHITECT Anti-TPO Reagent Kit must be stored • Patient specimens with a cloudy or turbid appearance must be centrifuged
at 2-8°C in an upright position and may be used prior to testing. Following centrifugation, avoid the lipid layer (if present)
immediately after removal from 2-8°C storage. when pipetting the specimen into a sample cup or secondary tube.
• When stored and handled as directed, reagents are stable until the • Specimens must be mixed THOROUGHLY after thawing by LOW speed
expiration date. vortexing or by gently inverting, and centrifuged prior to use to remove
• The ARCHITECT Anti-TPO Reagent Kit may be stored on board the red blood cells or particulate matter to ensure consistency in the results.
ARCHITECT i System for a maximum of 30 days. After 30 days, the Multiple freeze-thaw cycles of specimens should be avoided.
reagent kit must be discarded. For information on tracking onboard time, • All samples (patient specimens, controls, and calibrators) should be tested
refer to the ARCHITECT System Operations Manual, Section 5. within 3 hours of being placed on board the ARCHITECT System. Refer
• Reagents may be stored on or off the ARCHITECT i System. If reagents to the ARCHITECT System Operations Manual, Section 5, for a more
are removed from the system, store them at 2-8°C (with septa and detailed discussion of onboard sample storage constraints.
replacement caps) in an upright position. For reagents stored off the
system, it is recommended that they be stored in their original trays and Storage
boxes to ensure they remain upright. If the microparticle bottle does • If testing will be delayed for more than 8 hours, remove serum or plasma
not remain upright (with a septum installed) while in refrigerated from the serum or plasma separator, red blood cells or clot. Specimens
storage off the system, the reagent kit must be discarded. After removed from the separator gel, cells or clot may be stored up to
reagents are removed from the system, one must initiate a scan to update 72 hours at 2-8°C.
the onboard stability timer. • Specimens can be stored up to 30 days frozen at -10°C or colder.

Indications of Reagent Deterioration Shipping

When a control value is out of the specified range, it may indicate deterioration • Before shipping specimens, it is recommended that specimens be
of the reagents or errors in technique. Associated test results are invalid and removed from the serum or plasma separator, red blood cells or clot.
must be retested. Assay recalibration may be necessary. For troubleshooting When shipped, specimens must be packaged and labeled in compliance
information, refer to the ARCHITECT System Operations Manual, with applicable state, federal and international regulations covering the
Section 10. transport of clinical specimens and infectious substances. Specimens
must be shipped frozen (dry ice). Do not exceed the storage time
INSTRUMENT PROCEDURE limitations identified in this section of the package insert.
• The ARCHITECT Anti-TPO assay file must be installed on the
ARCHITECT i System from the ARCHITECT i Assay CD-ROM Addition B
PROCEDURE
prior to performing the assay. For detailed information on assay file Materials Provided:
installation and on viewing and editing assay parameters, refer to the • 2K47 ARCHITECT Anti-TPO Reagent Kit
ARCHITECT System Operations Manual, Section 2.
Materials Required but not Provided:
• For information on printing assay parameters, refer to the ARCHITECT
System Operations Manual, Section 5. • ARCHITECT i System
• For a detailed description of system procedures, refer to the ARCHITECT • 3K53 ARCHITECT i WW (excluding US) Addition B
System Operations Manual. • 2K47-01 ARCHITECT Anti-TPO Calibrators
• The default result unit for the ARCHITECT Anti-TPO assay is IU/mL.
• 2K47-10 ARCHITECT Anti-TPO Controls
SPECIMEN COLLECTION AND PREPARATION FOR ANALYSIS • ARCHITECT i
Specimen Types
• ARCHITECT i
• The following specimen collection tubes may be used in the ARCHITECT
Anti-TPO assay. • ARCHITECT i
Glass Plastic • ARCHITECT i
Serum • No additive (uncoated) • Serum separator tubes • ARCHITECT i
• Lithium heparin • Lithium heparin • ARCHITECT i
• Plasma separator tubes • Plasma separator tubes with
• ARCHITECT i
Plasma with lithium heparin lithium heparin
• EDTA • Sodium heparin • Pipettes or pipette tips (optional)
• EDTA For information on materials required for maintenance procedures, refer to
the ARCHITECT System Operations Manual, Section 9.
Other anticoagulants have not been validated for use with the ARCHITECT
Anti-TPO assay. Follow the manufacturer’s processing instructions for serum Assay Procedure
or plasma collection tubes. • Before loading the ARCHITECT Anti-TPO Reagent Kit on the system for
• When serial specimens are being evaluated, the same type of specimen the first time, the microparticle bottle requires mixing to resuspend
should be used throughout the study. microparticles that have settled during shipment.
• The ARCHITECT i System does not provide the capability to verify • Invert the microparticle bottle 30 times.
specimen type. It is the responsibility of the operator to verify the correct • Visually inspect the bottle to ensure microparticles are resuspended.
specimen types are used in the ARCHITECT Anti-TPO assay. If microparticles remain adhered to the bottle, continue to invert the
Specimen Conditions bottle until the microparticles have been completely resuspended.
• If the microparticles do not resuspend, DO NOT USE. Contact
• Do not use specimens with the following conditions:
your local Abbott Laboratories representative.
• heat-inactivated specimens
• Once the microparticles have been resuspended, remove and discard
• cadaver specimens or body fluids other than human serum or plasma
the cap. Wearing clean gloves, remove a septum from the bag.
• obvious microbial contamination
Squeeze the septum in half to confirm that the slits are open. Carefully
• Use caution when handling patient specimens to prevent cross
snap the septum onto the top of the bottle.
contamination. Use of disposable pipettes or pipette tips is recommended.
• Order calibration, if necessary.
• Inspect all samples for bubbles. Remove bubbles with an applicator stick
• For information on ordering calibrations, refer to the ARCHITECT
prior to analysis. Use a new applicator stick for each sample to prevent
System Operations Manual, Section 6.
cross contamination.
• Order tests.
• Serum and plasma specimens should be free of fibrin, red blood cells or
• For information on ordering patient specimens and controls, refer to
other particulate matter.
the ARCHITECT System Operations Manual, Section 5.
• Ensure that complete clot formation in serum specimens has taken place
• Load the ARCHITECT Anti-TPO Reagent Kit on the ARCHITECT i System.
prior to centrifugation. Some specimens, especially those from patients
• Verify that all necessary assay reagents are present. Ensure that
receiving anticoagulant or thrombolytic therapy, may exhibit increased
septa are present on all reagent bottles.
clotting time. If the specimen is centrifuged before a complete clot forms,
the presence of fibrin may cause erroneous results.

3
• The minimum sample volume is calculated by the system and is printed Calibration
on the Orderlist report. No more than 10 replicates may be sampled • To perform an ARCHITECT Anti-TPO calibration, test Calibrators A, B, C,
from the same sample cup. Verify adequate sample cup volume is present D, E, and F in duplicate. A single sample of each ARCHITECT
prior to running the test. Anti-TPO Control level must be tested to evaluate the assay calibration.
• Priority: 75 µL for the first ARCHITECT Anti-TPO test plus 25 µL Ensure that assay control values are within the concentration ranges
for each additional ARCHITECT Anti-TPO test from the same specified in the control package insert. Calibrators should be priority
sample cup. loaded.
• < 3 hours on board: 150 µL for the first ARCHITECT Anti-TPO test • Calibration Range: 0.00 - 1000.00 IU/mL.
plus 25 µL for each additional ARCHITECT Anti-TPO test from the • Once an ARCHITECT Anti-TPO calibration is accepted and stored, all
same sample cup. subsequent samples may be tested without further calibration unless:
• To minimize the effects of evaporation, all samples (patient specimens, • A reagent kit with a new lot number is used.
calibrators and controls) must be tested within 3 hours of being placed • Controls are out of range.
on board the ARCHITECT i System. • For detailed information on how to perform an assay calibration, refer to
• If using primary or aliquot tubes, use the sample gauge to ensure the ARCHITECT System Operations Manual, Section 6.
sufficient patient specimen is present.
• Prepare Calibrators and Controls. QUALITY CONTROL PROCEDURES
• ARCHITECT Anti-TPO Calibrators and Controls should be prepared The recommended control requirement for the ARCHITECT Anti-TPO assay
according to their respective package inserts. is a single sample of each control level be tested once every 24 hours each
• To obtain the recommended volume requirements for the ARCHITECT day of use. If the quality control procedures in your laboratory require more
Anti-TPO Calibrators and Controls, hold the bottles vertically and frequent use of controls to verify test results, follow your laboratory-specific
dispense 5 drops of each calibrator or control into each respective procedures.
sample cup. The ARCHITECT Anti-TPO Control values must be within the acceptable
• Load samples. ranges specified in the control package insert. If a control is out of its specified
• For information on loading samples, refer to the ARCHITECT System range, the associated test results are invalid and must be retested.
Operations Manual, Section 5. Recalibration may be indicated.
• Press RUN. The system performs the following functions:
Verification of Assay Claims
• Moves the sample to the aspiration point.
• Loads a reaction vessel (RV) into the process path. For protocols to verify package insert claims, refer to the ARCHITECT System
• Aspirates and transfers sample into the RV. Operations Manual, Appendix B. The ARCHITECT Anti-TPO assay belongs
• Advances the RV one position and transfers assay diluent and to method group 1. Use ARCHITECT Anti-TPO Calibrators in place of
microparticles into the RV. MasterCheck® as described in the ARCHITECT System Operations Manual,
• Mixes, incubates, and washes the reaction mixture. Appendix B.
• Adds conjugate to the RV. RESULTS
• Mixes, incubates, and washes the reaction mixture.
Calculation
• Adds pre-trigger and trigger solutions.
• Measures chemiluminescent emission to determine the quantity of The ARCHITECT Anti-TPO assay uses a 4 Parameter Logistic Curve Fit
anti-TPO in the sample. (4PLC, Y-weighted) data reduction method to generate a calibration curve.
• Aspirates contents of RV to liquid waste and unloads RV to solid Flags
waste. • Some results may contain information in the Flags field. For a description
• Calculates the result. of the flags that may appear in this field, refer to the ARCHITECT System
• For optimal performance, it is important to follow the routine maintenance Operations Manual, Section 5.
procedures defined in the ARCHITECT System Operations Manual,
Section 9. If your laboratory requires more frequent maintenance, follow LIMITATIONS OF THE PROCEDURE
those procedures. • Antibody measurement represents one parameter in a multi-criteria
diagnostic process. When making a diagnosis of thyroid disease, a
Specimen Dilution Procedures
combination of test methods should be used in conjunction with clinical
Specimens with an anti-TPO value exceeding 1000.00 IU/mL are flagged symptoms.
with the code “>1000.00” and may be diluted with the Automated Dilution • About 20% of asymptomatic specimens may present with anti-TPO
Protocol or the Manual Dilution Procedure. autoantibodies reflecting the prevalence in apparently healthy populations.
Automated Dilution Protocol The prevalence of anti-TPO may also depend on age, gender, and
• If using the Automated Dilution Protocol, the system performs a 1:2 dilution geographic region of the selected population.
of the specimen and automatically calculates the concentration of the • Some specimens may not dilute linearly because of the heterogeneity of
specimen before dilution and reports the result. the autoantibodies with respect to physiochemical properties.
• Specimens with an anti-TPO value exceeding 2000.00 IU/mL are flagged • Specimens from patients who have received preparations of mouse
with the code “>2000.00” when run using the Automated Dilution Protocol. monoclonal antibodies for diagnosis or therapy may contain human anti-
These specimens may be diluted by following the Manual Dilution mouse antibodies (HAMA).28 Such specimens may show either falsely
Procedure. elevated or depressed values when tested with assay kits that employ
mouse monoclonal antibodies.28,29 Assay results that are not consistent
Manual Dilution Procedure with other clinical observations may require additional information for
• Manual dilutions should be performed as follows: diagnosis.
• The suggested dilution for an anti-TPO test is 1:20. • Heterophilic antibodies in human serum can react with reagent
• Prior to diluting the specimen, dispense approximately 10 drops of immunoglobulins, interfering with in vitro immunoassays.30 The presence
ARCHITECT Anti-TPO Calibrator A into a clean test tube for use in of heterophilic antibodies in a patient specimen may cause anomalous
the next step. values to be observed.30 Additional information may be required for
• Transfer 190 µL of ARCHITECT Anti-TPO Calibrator A from the test diagnosis.
tube prepared in the prior step into another clean test tube and add
10 µL of the patient specimen. EXPECTED VALUES
• The operator must enter the dilution factor in the Patient or Control In a study, human serum specimens were collected from a population of 236
order screen. The system will use this dilution factor to automatically apparently healthy individuals. All specimens delivered TSH values within
calculate the concentration of the sample before dilution. This will be the normal reference range. Of this study population, 9 specimens delivered
the reported result. The dilution should be performed so that the diluted positive results on a commercially available anti-TPO assay device and were
result (before the dilution factor is applied) reads greater than excluded from further normal range analysis. The 97.5 percentile
5.61 IU/mL. concentration of the remaining population was 5.61 IU/mL. In this study
• For detailed information on ordering dilutions, refer to the ARCHITECT population, the normal range is < 5.61 IU/mL. A total of 97.8% (222/227) of
System Operations Manual, Section 5. the population gave values within this normal range.* This normal range is
suggested as a guideline and each laboratory should establish a normal
range appropriate to their patient populations, giving due consideration to
age, gender, geographical location and their clinical practice.
* Representative data; results in individual laboratories may vary from these data.

4
 Linearity
SPECIFIC PERFORMANCE CHARACTERISTICS
The ARCHITECT Anti-TPO assay is linear between 3.0 and 1000.0 IU/mL
Precision based on a study performed with guidance from NCCLS protocol
The ARCHITECT Anti-TPO assay is designed to have an assay precision of EP6-A. 32
< 10% total CV for samples > 5.61 IU/mL.
A study was performed for the ARCHITECT Anti-TPO assay with guidance Autodilution Verification
from the National Committee for Clinical Laboratory Standards (NCCLS) The ARCHITECT Anti-TPO automated dilution protocol is designed to recover
Protocol EP5-A.31 ARCHITECT Anti-TPO Positive Control and three human within 15% of manually diluted specimens. In a study, the automated dilution
panels were assayed using three lots of reagents in replicates of two at two protocol (1:2) was compared to a manual 1:2 dilution procedure using 9
separate times per day for 20 days on three instruments. Each reagent lot human specimens with anti-TPO levels that were greater than Calibrator E
used a single calibration curve throughout the study. Data from this study (250 IU/mL). The manual dilution was performed with ARCHITECT Anti-
are summarized in the following table.* TPO Calibrator A. The observed percent recovery results are summarized
in the following table.*
Mean
Reagent Conc. Within Run Total Automated Manual Dilution
Sample Instrument Lot n (IU/mL) SD %CV SD %CV Sample ID Dilution (IU/mL) (IU/mL) % Recovery**

1 A 80 74.85 2.11 2.8 2.16 2.9 1 861.25 859.27 100.2

B 80 74.20 1.89 2.6 2.04 2.7 2 684.49 703.64 97.3
C 80 74.63 2.01 2.7 2.17 2.9 3 844.36 847.62 99.6
2 A 80 77.42 2.11 2.7 3.25 4.2 4 724.55 757.09 95.7
Positive B 80 75.32 1.92 2.5 2.54 3.4 5 709.46 688.49 103.1
Control C 80 74.59 1.73 2.3 2.57 3.4 6 1105.65 1106.18 100.0
3 A 80 75.41 2.13 2.8 2.52 3.3 7 948.43 931.80 101.8
B 80 75.48 1.90 2.5 2.13 2.8 8 840.77 851.72 98.7
C 80 76.66 2.42 3.2 2.87 3.7 9 966.48 998.45 96.8

1 A 80 1.57 0.08 4.8 0.10 6.5 * Representative data; results in individual laboratories may vary from these data.
B 80 1.46 0.06 3.8 0.09 5.8
Automated Dilution (IU/mL)
C 80 1.64 0.09 5.6 0.10 6.1 **% Recovery = ––––––––––––––––––––––– x 100
Panel 1 2 A 80 1.60 0.09 5.3 0.12 7.6 Manual Dilution (IU/mL)
B 80 1.53 0.06 3.9 0.11 7.2
Interference
C 80 1.52 0.10 6.7 0.12 7.7
Interference from elevated levels of bilirubin, hemoglobin, triglycerides, and
3 A 80 1.47 0.08 5.3 0.11 7.8
total protein in the ARCHITECT Anti-TPO assay is designed to be < 15% at
B 80 1.47 0.07 4.7 0.13 8.5
the levels indicated.
C 80 1.52 0.14 9.5 0.15 9.8
A study based on guidance from the NCCLS Protocol EP7-A33 was performed
1 A 80 20.98 0.65 3.1 0.76 3.6 for the ARCHITECT Anti-TPO assay. Specimens with anti-TPO levels
B 80 21.14 0.61 2.9 0.66 3.1 between 45.07 and 361.64 IU/mL were supplemented with the following
C 80 21.51 0.71 3.3 0.75 3.5 potentially interfering compounds. The average amount of interference
2 A 80 21.27 0.61 2.9 0.98 4.6 observed during the study ranged from -3.6% to +3.7%.*
Panel 2 B 80 21.62 0.66 3.0 0.90 4.2
C 80 20.82 0.67 3.2 0.85 4.1 Potentially Interfering Potentially Interfering
3 A 80 21.00 0.73 3.5 0.86 4.1 Substance Substance Concentration
B 80 21.77 0.60 2.7 0.84 3.8 Bilirubin 20 mg/dL
C 80 21.24 0.70 3.3 0.89 4.2 Hemoglobin 1000 mg/dL
1 A 80 214.78 5.14 2.4 6.48 3.0 Total Protein (Low) 4 g/dL
B 80 221.79 4.73 2.1 5.82 2.6 Total Protein (High) 10 g/dL
C 80 216.71 5.36 2.5 6.36 2.9 Triglycerides 1000 mg/dL
2 A 80 219.32 4.41 2.0 8.61 3.9 * Representative data; results in individual laboratories may vary from these data.
Panel 3 B 80 224.54 4.04 1.8 13.37 6.0
Evaluation of Autoimmune Disease Specimens and High Titer IgG Samples
C 80 218.73 5.76 2.6 13.18 6.0
3 A 80 212.91 6.11 2.9 6.84 3.2 Potential interference from autoimmune disease specimens and high titer IgG
B 80 225.46 5.15 2.3 5.67 2.5 samples in the ARCHITECT Anti-TPO assay is designed to be < 15%. In a
C 80 228.17 5.80 2.5 7.09 3.1 study, the ARCHITECT Anti-TPO assay was evaluated by testing specimens
with known autoimmune diseases and elevated IgG. Specimens were
*Representative data; results in individual laboratories may vary from these data. evaluated with anti-TPO levels spiked between 131.44 and 568.78 IU/mL.
Functional Sensitivity Mean absolute % interference is summarized in the following table.*
In a study, human panels ranging in concentration from 0.16-1.20 IU/mL Clinical Condition Mean Absolute % Interference
were tested in replicates of 2 over 10 days on one instrument using two
reagent lots and three calibrations for a total of 40 replicates per panel. The Anti-Nuclear Antibody (ANA) 1.6
total %CVs (combining variance components for replicate, run, day and Rheumatoid Arthritis (RA) 1.6
reagent lot) were calculated and plotted against the mean concentration. A Systemic Lupus Erythematosus (SLE) 1.1
reciprocal curve was fitted through the data and the functional sensitivity Insulin Dependent Diabetes Mellitus (IDDM) 1.0
value was calculated as the concentration corresponding to the 20% CV Crohn’s Disease 2.4
level of the fitted curve. The lowest ARCHITECT Anti-TPO assay value Multiple Sclerosis 1.7
exhibiting a 20% CV is 0.50 IU/mL.* Ulcerative Colitis 1.5
* Representative data; results in individual laboratories may vary from these data. Hyperglobulinemia (high IgG) 0.9
* Representative data; results in individual laboratories may vary from these data.
Analytical Sensitivity
The ARCHITECT Anti-TPO assay is designed to have an analytical sensitivity
of < 1.0 IU/mL. The analytical sensitivity of the ARCHITECT Anti-TPO assay,
defined as the concentration at two standard deviations above the ARCHITECT
Anti-TPO Calibrator A (0.0 IU/mL) was calculated to be 0.16 IU/mL* at the
95% level of confidence (based upon one study with n=48 runs, 10 replicates
of Calibrator A and 4 replicates of Calibrator B per run).
* Representative data; results in individual laboratories may vary from these data.

5
Evaluation of Other Potential Interferents 11. Banga JP, Pryce G, Hammond L, et al. Structural features of the
Potential interference from HAMA and rheumatoid factor (RF) in the autoantigens involved in thyroid autoimmune disease: the thyroid
ARCHITECT Anti-TPO assay is designed to be < 15%. In a study, the microsomal / microvillar antigen. Mol Immunol 1985;22(6):629-42.
ARCHITECT Anti-TPO assay was evaluated by testing specimens with HAMA 12. Davies TF, Weiss I. Autoimmune thyroid disease and pregnancy. Am J
and RF to further assess the clinical specificity. Specimens positive for HAMA Reprod Immunol 1981;1:187-92.
and specimens positive for RF were evaluated for % interference with 13. Amino N, Yabu Y, Miki T, et al. Serum ratio of triiodothyronine to thyroxine,
anti-TPO levels spiked between 163.0 and 184.3 IU/mL. Mean absolute % and thyroxine-binding globulin and calcitonin concentrations in Graves’
interference is summarized in the following table.* disease and destruction-induced thyrotoxicosis. J Clin Endocrinol Metab
1981;53(1):113-6.
Other Potential Interferents Number of Mean Absolute 14. Jansson R, Bernander S, Karlsson A, et al. Autoimmune thyroid
Specimens % Interference dysfunction in the postpartum period. J Clin Endocrinol Metab
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The performance of the ARCHITECT Anti-TPO was compared to a
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commercially available immunoassay for the determination of anti-TPO. A
23. Mariotti S, Chiovato L, Franceschi C, et al. Thyroid autoimmunity and
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of apparently healthy individuals and patients with autoimmune thyroid
24. US Department of Labor, Occupational Safety and Health Administration,
disease (Graves’ disease and Hashimoto’s thyroiditis). Specimens were
29 CFR Part 1910.1030, Occupational Exposure to Bloodborne
tested in replicates of one using the ARCHITECT Anti-TPO assay with three
Pathogens.
reagent lots on three instruments and compared with a commercially available
25. US Department of Health and Human Services. Biosafety in
immunoassay (Comparison Assay). Data from this study are summarized in
Microbiological and Biomedical Laboratories, Fourth Edition.
the following table.*
Washington, DC: US Government Printing Office, May 1999.
Comparison Assay 26. World Health Organization. Laboratory Biosafety Manual. Geneva: World
ARCHITECT Anti-TPO Negative Positive Health Organization; 2004.
Negative 242 32
27. Clinical and Laboratory Standards Institute. Protection of Laboratory
Positive 5 221
Workers from Occupationally Acquired Infections: Approved Guideline
– Third Edition. CLSI Document M29-A3. Wayne, PA: Clinical and
Concordance = 92.6 % Laboratory Standards Institute, 2005.
* Representative data; results in individual laboratories may vary from these data. 28. Schroff RW, Foon KA, Beatty SM, et al. Human anti-murine
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