SYSTEM

E
Anti-Tg
2K46
840240/R4

Anti-Tg
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, 2006 Abbott Laboratories / ARCHITECT Anti-Tg

May 2006

Key to symbols used

List Number Lot Number

For In Vitro Diagnostic Use Expiration Date

Reaction Vessels
Store at 2-8°C
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-Tg ARCHITECT i Pre-Trigger Solution
INTENDED USE • Pre-Trigger Solution containing 1.32%
ARCHITECT Anti-Tg is a Chemiluminescent Microparticle Immunoassay (w/v) hydrogen peroxide.
(CMIA) for the quantitative determination of the IgG class of thyroglobulin ARCHITECT i Trigger Solution
autoantibodies (anti-Tg) in human serum and plasma on the ARCHITECT i
System. The ARCHITECT Anti-Tg assay is intended for use as an aid in the • Trigger Solution containing 0.35N sodium
diagnosis of autoimmune thyroid disease. hydroxide.

SUMMARY AND EXPLANATION OF TEST ARCHITECT i Wash Buffer

Autoimmune thyroiditis was first described by Hashimoto in 19121 and • Wash Buffer containing phosphate buffered saline
autoimmune thyroid disease with associated goitre is termed Hashimoto’s solution. Preservative: antimicrobial agent.
thyroiditis. The presence of anti-Tg in patients with this disease was first
demonstrated in 1956 by Roitt, et al2 using a precipitin reaction. Unlike WARNINGS AND PRECAUTIONS
autoantibodies to thyroid peroxidase (anti-TPO), autoantibodies to For In Vitro Diagnostic Use.
thyroglobulin do not appear to be pathogenic and may simply be indicators
of disease.3 They have been found to be polyclonal in nature and are also Safety Precautions
heterogeneous with respect to heavy chain subclass.4-9
Thyroglobulin is a glycoprotein of 670,000 daltons, which is comprised of • CAUTION: This product contains human sourced and/or potentially
two identical subunits and represents the major protein found in the thyroid. infectious components. For a specific listing, refer to the REAGENTS
This protein provides 40 tyrosine residues, of the 140 in the molecule, used section of this package insert. No known test method can offer complete
for iodination during the biosynthesis of thyroxine (T4) and triiodothyronine assurance that products derived from human sources or inactivated
(T3) and, therefore, is responsible for the accumulation of iodine by the microorganisms will not transmit infection. Therefore, all human sourced
thyroid gland.10 materials should be considered potentially infectious. It is recommended
Although anti-Tg are found in conjunction with anti-TPO in the majority of that these reagents and human specimens be handled in accordance
cases of Hashimoto’s thyroiditis, Primary Myxedema and Graves’ with the OSHA Standard on Bloodborne Pathogens21. Biosafety Level 222
disease,11,12 up to 1% of cases of hypothyroidism are associated with anti-Tg or other appropriate biosafety practices 23,24 should be used for materials
alone.13 Anti-Tg are associated with cases of mild hypothyroidism or that contain or are suspected of containing infectious agents.
hyperthyroidism, and are frequently found in patients with other autoimmune • The ARCHITECT i Trigger Solution contains sodium hydroxide (NaOH)
diseases such as Rheumatoid Arthritis, Pernicious Anaemia and Type I and is classified per applicable European Community (EC) Directives
Diabetes.14-16 Anti-Tg are detected in 30-60% of cases of thyroid carcinoma as: Irritant (Xi). The following are the appropriate Risk (R) and Safety (S)
patients. In such patients, measurement of Tg antigen must take into account phrases.
the likelihood of the presence of significant levels of anti-Tg, since R41 Risk of serious damage to eyes.
measurement and detection of Tg antigen may be influenced by the presence S25 Avoid contact with eyes.
S26 In case of contact with eyes, rinse immediately with
of anti-Tg.17,18
plenty of water and seek medical advice.
Furthermore, low levels of anti-Tg are also found in up to 20% of asymptomatic
S35 This material and its container must be disposed of in
individuals, particularly the elderly and more often in women than men, a safe way.
although the clinical significance of these autoantibodies is unclear.19,20 S36/39 Wear suitable protective clothing and eye/face
protection.
BIOLOGICAL PRINCIPLES OF THE PROCEDURE
S46 If swallowed, seek medical advice immediately and
The ARCHITECT Anti-Tg assay is a two-step immunoassay for the show this container or label.
quantitative determination of the IgG class of thyroglobulin autoantibodies
• For product not classified as dangerous per European Directive
(anti-Tg) in human serum and plasma using CMIA technology with flexible
1999/45/EC as amended - Safety data sheet available for professional
assay protocols, referred to as Chemiflex®.
user on request.
In the first step, sample, assay diluent and Tg coated paramagnetic
microparticles are combined and incubated. Anti-Tg present in the sample Handling Precautions
binds to the Tg 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-Tg Reagent Kit on the system for
reaction mixture. The resulting chemiluminescent reaction is measured as 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-Tg in the sample and the RLUs detected by the ARCHITECT i* system instructions, refer to the PROCEDURE, Assay Procedure section of
optics. this package insert.
For additional information on system and assay technology, refer to the • Septa MUST be used to prevent reagent evaporation and
ARCHITECT System Operations Manual, Section 3. contamination and to ensure reagent integrity. Reliability of assay
* i = immunoassay results cannot be guaranteed if septa are not used according to the
instructions in this package insert.
REAGENTS • To avoid contamination, wear clean gloves when placing a septum
Reagent Kit, 100 Tests on an uncapped reagent bottle.
NOTE: Some kit sizes are not available in all countries; please contact your • Prior to placing the septum on an uncapped reagent bottle, squeeze the
local distributor. septum in half to confirm that the slits are open. If the slits appear sealed,
ARCHITECT Anti-Tg Reagent Kit (2K46) continue to gently squeeze the septum to open the slits.
• Once a septum has been placed on an open reagent bottle, do not
• 1 or 4 Bottles (6.6 mL) Human thyroglobulin (tested invert the bottle as this will result in reagent leakage and may
and found to be nonreactive to HBsAg, anti-HCV and anti-HIV-1/HIV-2) compromise assay results.
coated microparticles in MES buffer with protein (goat) stabilizer. • Over time, residual liquids may dry on the septum surface. These are
Preservative: antimicrobial agents. typically dried salts which have no effect on assay efficacy.
• 1 or 4 Bottles (5.9 mL) Anti-human IgG (mouse, • For a detailed discussion of handling precautions during system operation,
monoclonal) acridinium labeled conjugate in MES buffer with protein refer to the ARCHITECT System Operations Manual, Section 7.
(bovine) stabilizer. Preservative: antimicrobial agents.
• 1 or 4 Bottles (10.0 mL) Assay Diluent in MES buffer
with protein (goat). Preservative: antimicrobial agents.

2
Storage Instructions Preparation for Analysis
• The ARCHITECT Anti-Tg Reagent Kit must be stored at • Patient specimens with a cloudy or turbid appearance must be centrifuged
2-8°C in an upright position and may be used immediately prior to testing. Following centrifugation, avoid the lipid layer (if present)
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-Tg 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. Recalibration may be required to obtain • All samples (patient specimens, controls, and calibrators) should be tested
maximum onboard reagent stability. For information on tracking onboard within 3 hours of being placed on board the ARCHITECT i System. Refer
time, refer to the ARCHITECT System Operations Manual, Section 5. to the ARCHITECT System Operations Manual, Section 5, for a more
• Reagents may be stored on or off the ARCHITECT i System. If reagents detailed discussion of onboard sample storage constraints.
are removed from the system, store them at 2-8°C (with septa and
replacement caps) in an upright position. For reagents stored off the Storage
system, it is recommended that they be stored in their original trays and • If testing will be delayed for more than 8 hours, remove serum or plasma
boxes to ensure they remain upright. If the microparticle bottle does from the serum or plasma separator, red blood cells or clot. Specimens
not remain upright (with a septum installed) while in refrigerated removed from the separator gel, cells or clot may be stored up to
storage off the system, the reagent kit must be discarded. After 72 hours at 2-8°C.
reagents are removed from the system, one must initiate a scan to update • Specimens can be stored up to 30 days frozen at -10°C or colder.
the onboard stability timer. Shipping
Indications of Reagent Deterioration • Before shipping specimens, it is recommended that specimens be
When a control value is out of the specified range, it may indicate deterioration removed from the serum or plasma separator, red blood cells or clot.
of the reagents or errors in technique. Associated test results are invalid and When shipped, specimens must be packaged and labeled in compliance
must be retested. Assay recalibration may be necessary. For troubleshooting with applicable state, federal and international regulations covering the
information, refer to the ARCHITECT System Operations Manual, 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-Tg assay file must be installed on the ARCHITECT i
System from the ARCHITECT i Assay CD-ROM Addition B prior to
PROCEDURE
performing the assay. For detailed information on assay file installation Materials Provided:
and on viewing and editing assay parameters, refer to the ARCHITECT • 2K46 ARCHITECT Anti-Tg Reagent Kit
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 • 3K51 ARCHITECT i - US - Addition B
System Operations Manual. • 3K53 ARCHITECT i WW (excluding US) Addition B
• The default result unit for the ARCHITECT Anti-Tg assay is IU/mL. • 2K46-01 ARCHITECT Anti-Tg Calibrators
• 2K46-10 ARCHITECT Anti-Tg Controls
SPECIMEN COLLECTION AND PREPARATION FOR ANALYSIS
• ARCHITECT i
Specimen Types • ARCHITECT i
• The following specimen collection tubes may be used in the ARCHITECT
• ARCHITECT i
Anti-Tg assay. Interference from all tube types listed below, when
compared with serum in uncoated glass (no additive), was less than 10%. • ARCHITECT i
Glass Plastic • ARCHITECT i
Serum • No additive (uncoated) • Serum separator tubes • ARCHITECT i
• ARCHITECT i
• Lithium heparin • Lithium heparin
• Pipettes or pipette tips (optional)
• Plasma separator tubes • Plasma separator tubes with
Plasma with lithium heparin lithium heparin For information on materials required for maintenance procedures, refer to
• EDTA • Sodium heparin the ARCHITECT System Operations Manual, Section 9.
• EDTA Assay Procedure
Other anticoagulants have not been validated for use with the ARCHITECT • Before loading the ARCHITECT Anti-Tg Reagent Kit on the system for
Anti-Tg assay. Follow the manufacturer’s processing instructions for serum the first time, the microparticle bottle requires mixing to resuspend
or plasma collection tubes. microparticles that have settled during shipment.
• When serial specimens are being evaluated, the same type of specimen • Invert the microparticle bottle 30 times.
should be used throughout the study. • Visually inspect the bottle to ensure microparticles are resuspended.
• The ARCHITECT i System does not provide the capability to verify If microparticles remain adhered to the bottle, continue to invert the
specimen type. It is the responsibility of the operator to verify the correct bottle until the microparticles have been completely resuspended.
specimen types are used in the ARCHITECT Anti-Tg assay. • If the microparticles do not resuspend, DO NOT USE. Contact
your local Abbott Laboratories representative.
Specimen Conditions
• Once the microparticles have been resuspended, remove and discard
• Do not use specimens with the following conditions: the cap. Wearing clean gloves, remove a septum from the bag.
• heat-inactivated specimens Squeeze the septum in half to confirm that the slits are open. Carefully
• cadaver specimens or body fluids other than human serum or plasma snap the septum onto the top of the bottle.
• obvious microbial contamination • Order calibration, if necessary.
• Use caution when handling patient specimens to prevent cross • For information on ordering calibrations, refer to the ARCHITECT
contamination. Use of disposable pipettes or pipette tips is recommended. System Operations Manual, Section 6.
• Inspect all samples for bubbles. Remove bubbles with an applicator stick • Order tests.
prior to analysis. Use a new applicator stick for each sample to prevent • For information on ordering patient specimens and controls, refer to
cross contamination. the ARCHITECT System Operations Manual, Section 5.
• Serum and plasma specimens should be free of fibrin, red blood cells or • Load the ARCHITECT Anti-Tg Reagent Kit on the ARCHITECT i System.
other particulate matter. • Verify that all necessary assay reagents are present. Ensure that
• Ensure that complete clot formation in serum specimens has taken place septa are present on all reagent bottles.
prior to centrifugation. Some specimens, especially those from patients
receiving anticoagulant or thrombolytic therapy, may exhibit increased
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-Tg 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 Anti-Tg
prior to running the test. Control level must be tested to evaluate the assay calibration. Ensure
• Priority: 75 µL for the first ARCHITECT Anti-Tg test plus 25 µL for that assay control values are within the concentration ranges specified
each additional ARCHITECT Anti-Tg test from the same sample cup. in the control package insert. Calibrators should be priority loaded.
• < 3 hours on board: 150 µL for the first ARCHITECT Anti-Tg test plus • Calibration Range: 0.0 - 1000.0 IU/mL.
25 µL for each additional ARCHITECT Anti-Tg test from the same • Once an ARCHITECT Anti-Tg calibration is accepted and stored, all
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-Tg Calibrators and Controls should be prepared The recommended control requirement for the ARCHITECT Anti-Tg 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-Tg 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-Tg Control values must be within the acceptable ranges
• Load samples. 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-Tg assay belongs to
• Advances the RV one position and transfers assay diluent and method group 1. Use ARCHITECT Anti-Tg 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-Tg assay uses a 4 Parameter Logistic Curve Fit (4PLC,
anti-Tg in the sample. 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-Tg value exceeding 1000.00 IU/mL are flagged with symptoms.
the code “>1000.00” and may be diluted with the Automated Dilution Protocol • About 20% of asymptomatic specimens may present with anti-Tg
or the Manual Dilution Procedure. autoantibodies reflecting the prevalence in apparently healthy
Automated Dilution Protocol populations. The prevalence of anti-Tg may also depend on age, gender,
• If using the Automated Dilution Protocol, the system performs a 1:10 and geographic region of the selected population.
dilution of the specimen and automatically calculates the concentration • Some specimens may not dilute linearly because of the heterogeneity of
of the specimen before dilution and reports the result. the autoantibodies with respect to physiochemical properties.
• Specimens with an anti-Tg value exceeding 10000.00 IU/mL are flagged • Specimens from patients who have received preparations of mouse
with the code “>10000.00” when run using the Automated Dilution monoclonal antibodies for diagnosis or therapy may contain human anti-
Protocol. These specimens may be diluted by following the Manual mouse antibodies (HAMA).25 Such specimens may show either falsely
Dilution Procedure. elevated or depressed values when tested with assay kits that employ
mouse monoclonal antibodies.25,26 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-Tg 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.27 The presence
ARCHITECT Anti-Tg Calibrator A into a clean test tube for use in the of heterophilic antibodies in a patient specimen may cause anomalous
next step. values to be observed.27 Additional information may be required for
• Transfer 190 µL of ARCHITECT Anti-Tg 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.
• The operator must enter the dilution factor in the Patient or Control
order screen. The system will use this dilution factor to automatically
calculate the concentration of the sample before dilution. This will be
the reported result. The dilution should be performed so that the diluted
result (before the dilution factor is applied) reads greater than
1.00 IU/mL.
• For detailed information on ordering dilutions, refer to the ARCHITECT
System Operations Manual, Section 5.

4
EXPECTED VALUES Functional Sensitivity
Human serum specimens were collected from a population of 234 apparently In a study, human panels ranging in concentration from 0.07-1.38 IU/mL
healthy individuals. All specimens delivered TSH values within the normal were tested in replicates of 2 over 10 days on one instrument using two
reference range. Of this study population, 6 specimens delivered positive reagent lots and three calibrations for a total of 40 replicates per panel. The
results on a commercially available anti-Tg assay device and were excluded total %CVs (combining variance components for replicate, run, day and
from further analysis. The 97.5 percentile concentration of the remaining reagent lot) were calculated and plotted against the mean concentration. A
population was 4.11 IU/mL. On the basis of this study population, the expected reciprocal curve was fitted through the data and the functional sensitivity
normal range is < 4.11 IU/mL. A total of 97.8% (223/228) of the population value was calculated as the concentration corresponding to the 20% CV
gave values within this expected normal range.* This normal range is level of the fitted curve. The lowest ARCHITECT Anti-Tg assay value
suggested as a guideline and each laboratory should establish a normal exhibiting a 20% CV is 0.31 IU/mL.*
range appropriate to their patient populations, giving due consideration to * Representative data; results in individual laboratories may vary from these
age, gender, geographical location and their clinical practice. data.
* Representative data; results in individual laboratories may vary from these
Sensitivity
data.
The ARCHITECT Anti-Tg assay is designed to have a limit of detection of
SPECIFIC PERFORMANCE CHARACTERISTICS < 1.0 IU/mL. The limit of detection of the ARCHITECT Anti-Tg assay, defined
Precision as the concentration at two standard deviations above the ARCHITECT Anti-Tg
The ARCHITECT Anti-Tg assay is designed to have an assay precision of Calibrator A (0.0 IU/mL) was calculated to be 0.07 IU/mL* at the 95% level of
< 10% total CV for samples > 4.0 IU/mL. confidence (based upon one study with n=48 runs, 10 replicates of
A study was performed with guidance from the National Committee for Clinical Calibrator A and 4 replicates of Calibrator B per run).
Laboratory Standards (NCCLS) Protocol EP5-A.28 ARCHITECT Anti-Tg * Representative data; results in individual laboratories may vary from these
data.
Positive Control and four human panels were assayed using three lots of
reagents in replicates of two at two separate times per day for 20 days on Linearity
three instruments. Each reagent lot used a single calibration curve throughout The ARCHITECT Anti-Tg assay is linear between 3.0 and 1000.0 IU/mL
the study. Data from this study are summarized in the following table.* based on a study performed with guidance from NCCLS protocol EP6-A.29
Mean Three high sample pools (1000, 300, and 30 IU/mL) were each combined
Sample Instrument Reagent n Conc. Within Run Total with a low pool (ARCHITECT Anti-Tg Calibrator A) to prepare nine sets of
Lot (IU/mL) SD % CV SD % CV test dilutions extending to 1/10th of the starting concentration. All of these
1 A 80 146.83 2.94 2.0 4.69 3.2 dilutions were analyzed with the ARCHITECT Anti-Tg assay using a single
B 80 150.99 3.13 2.1 4.53 3.0 reagent lot.
C 80 149.35 3.41 2.3 4.10 2.7
Autodilution Verification
2 A 80 151.19 3.81 2.5 4.22 2.8
Positive B 80 153.22 2.71 1.8 3.47 2.3 The ARCHITECT Anti-Tg automated dilution protocol is designed to recover
Control C 80 145.63 3.46 2.4 3.90 2.7 within 20% of manually diluted specimens.
3 A 80 146.23 2.85 2.0 4.76 3.3 In a study, the automated dilution protocol (1:10) was compared to a manual
B 80 149.41 3.14 2.1 4.15 2.8 1:10 dilution procedure using 6 human specimens with anti-Tg levels that
C 80 146.82 3.51 2.4 4.70 3.2 were greater than Calibrator E (500 IU/mL). The manual dilution was
performed with ARCHITECT Anti-Tg Calibrator A. The observed percent
1 A 80 4.16 0.15 3.6 0.21 5.0
B 80 4.12 0.11 2.7 0.13 3.1
recovery results are summarized in the following table.*
C 80 3.84 0.11 3.0 0.16 4.3 Automated Manual Dilution
2 A 80 4.08 0.18 4.4 0.25 6.2 Sample ID Dilution (IU/mL) (IU/mL) % Recovery**
Panel 1 B 80 3.78 0.11 2.9 0.14 3.7
C 80 3.88 0.13 3.5 0.17 4.5 1 2103.48 2132.50 98.6
3 A 80 4.26 0.17 4.0 0.27 6.2 2 1656.16 1649.87 100.4
B 80 4.26 0.11 2.7 0.20 4.8 3 732.79 621.43 117.9
C 80 3.73 0.11 3.0 0.21 5.7 4 557.55 561.10 99.4
5 994.66 973.70 102.2
1 A 80 17.27 0.45 2.6 0.62 3.6
6 526.18 562.63 93.5
B 80 17.38 0.80 4.6 0.85 4.9
C 80 16.99 0.38 2.3 0.50 3.0 * Representative data; results in individual laboratories may vary from these
2 A 80 17.46 0.49 2.8 0.66 3.8 data.
Panel 2 B 80 17.32 0.40 2.3 0.53 3.1 Automated Dilution (IU/mL)
C 80 17.16 0.41 2.4 0.56 3.3 ** % Recovery = ––––––––––––––––––––––– x 100
3 A 80 17.61 0.46 2.6 0.79 4.5 Manual Dilution (IU/mL)
B 80 17.80 0.44 2.5 0.67 3.7
C 80 16.68 0.48 2.9 0.94 5.6 Interference
Interference from elevated levels of bilirubin, hemoglobin, triglycerides, and
1 A 80 368.42 6.17 1.7 12.25 3.3
total protein in the ARCHITECT Anti-Tg assay is designed to be < 15% at
B 80 422.83 11.28 2.7 11.66 2.8
the levels indicated.
C 80 421.51 13.64 3.2 17.14 4.1
2 A 80 383.97 9.74 2.5 14.30 3.7
A study based on guidance from the NCCLS Protocol EP7-A30 was performed
Panel 5 B 80 441.17 12.54 2.8 21.81 4.9
for the ARCHITECT Anti-Tg assay. Specimens with anti-Tg levels between
C 80 406.97 12.36 3.0 19.00 4.7 53.41 and 320.25 IU/mL were supplemented with the following potentially
3 A 80 391.42 13.69 3.5 16.96 4.3 interfering compounds. The average amount of interference observed during
B 80 449.02 12.38 2.8 22.10 4.9 the study ranged from -3.8% to +1.7%.*
C 80 429.86 13.35 3.1 21.25 4.9 Potentially Interfering Potentially Interfering
1 A 80 739.28 21.82 3.0 28.40 3.8 Substance Substance Concentration
B 80 757.48 25.09 3.3 28.03 3.7
Bilirubin 20 mg/dL
C 80 753.34 33.05 4.4 35.69 4.7
Hemoglobin 1000 mg/dL
2 A 80 759.26 23.19 3.1 25.63 3.4
Total Protein (Low) 4 g/dL
Panel 6 B 80 794.80 27.45 3.5 29.58 3.7
Total Protein (High) 10 g/dL
C 80 737.07 23.92 3.2 28.95 3.9
3 A 80 827.71 55.03 6.6 68.26 8.2
Triglycerides 2000 mg/dL
B 80 842.48 30.16 3.6 51.23 6.1 * Representative data; results in individual laboratories may vary from these
C 80 765.29 37.90 5.0 45.10 5.9 data.
* Representative data; results in individual laboratories may vary from these
data.

5
Evaluation of Autoimmune Disease Specimens and High Titer IgG Samples BIBLIOGRAPHY
Potential interference from autoimmune disease specimens and high titer 1. Hashimoto H. Zur Kenntniss der lymphomat
sen Vernderung der
IgG samples in the ARCHITECT Anti-Tg assay is designed to be < 20%. In Schilddrse (Struma lymphomatosa). Arch Klin Chir 1912;97:219-48.
a study, the ARCHITECT Anti-Tg assay was evaluated by testing specimens 2. Roitt IM, Doniach D, Campbell PN, et al. Auto-antibodies in Hashimoto’s
with known autoimmune diseases and elevated IgG. Specimens were Disease (Lymphadenoid Goitre). Lancet 1956;6947:820-1.
evaluated with anti-Tg levels spiked between 175.58 and 235.86 IU/mL. 3. Tomer Y. Anti-thyroglobulin autoantibodies in autoimmune thyroid
Mean absolute % interference is summarized in the following table.* diseases: cross-reactive or pathogenic? Clin Immunol Immunopath
Clinical Condition Mean Absolute % Interference 1997;82:3-11.
4. Laing P. Both K and λ light chain types are present in thyroid microsomal
Anti-Nuclear Antibody (ANA) 1.2 and thyroglobulin autoantibodies. Proc Univ Otago Me. Sch.
Rheumatoid Arthritis (RA) 1.8 1983;61:75-7.
Systemic Lupus Erythematosus (SLE) 2.1 5. Nye L, Decarvalho LP, Roitt IM. An investigation of the clonality of human
Insulin Dependent Diabetes Mellitus (IDDM) 3.0 autoimmune thyroglobulin antibodies and their light chains. Clin Exp
Crohn’s Disease 2.5 Immunol 1981;46:161-70.
Multiple Sclerosis 3.6 6. Weetman AP, Black CM, Cohen SB, et al. Affinity purification of IgG
Ulcerative Colitis 2.6 subclasses and the distribution of thyroid auto-antibody reactivity in
Hyperglobulinemia (high IgG) 4.5 Hashimoto’s thyroiditis. Scan J Immunol 1989;30:73-82.
* Representative data; results in individual laboratories may vary from these 7. Weetman AP, Yateman ME, Ealey PA, et al. Thyroid-stimulating antibody
data. activity between different immunoglobulin G subclasses. J Clin Invest
1990;86:723-7.
Evaluation of Other Potential Interferents 8. Shimojo N, Saito K, Kohno Y, et al. Antigenic determinants on
Potential interference from HAMA and rheumatoid factor (RF) in the thyroglobulin: comparison of the reactivities of different thyroglobulin
ARCHITECT Anti-Tg assay is designed to be < 20%. In a study, the preparations with serum antibodies and T cells of patients with chronic
ARCHITECT Anti-Tg assay was evaluated by testing specimens with HAMA thyroiditis. J Clin Endocrinol Metab 1988;66(4):689-95.
and RF to further assess the clinical specificity. Specimens positive for HAMA 9. McIntosh RS, Asghar MS, Weetman AP. The antibody response in
and specimens positive for RF were evaluated for % interference with human autoimmune thyroid disease. Clinical Science 1997;92:529-41.
anti-Tg levels spiked between 218.05 and 235.86 IU/mL. Mean absolute % 10. DeGroot LJ, Larsen PR, Hennemann G, editors. Thyroid hormone
interference is summarized in the following table.* synthesis and secretion. In: The Thyroid and its Diseases 6th edition.
New York: Churchill Livingstone; 1996:45-8.
Other Potential Interferents Number of Mean Absolute
11. Rosenbaum D, Davies TF. The clinical use of thyroid autoantibodies.
Specimens % Interference
The Endocrinologist 1992;2(1):55-62.
HAMA Positive 10 1.3 12. Burek CL, Rose NR. Thyroglobulin autoantibodies. In: Peter JB and
RF Positive 10 1.8 Shoenfeld Y, editors. Autoantibodies. Amsterdam: Elsevier Science B.V.;
* Representative data; results in individual laboratories may vary from these 1996:810-5.
data. 13. Nordyke RA, Gilbert FI Jr, Miyamoto LA, et al. The superiority of
antimicrosomal over antithyroglobulin antibodies for detecting
Clinical Sensitivity Hashimoto’s thyroiditis. Arch Intern Med 1993;153:862-5.
In a study, clinical sensitivity was evaluated by testing 68 clinically defined 14. Ruf J, Feldt-Rasmussen U, Hegeds L, et al. Bispecific thyroglobulin
Hashimoto’s thyroiditis specimens and 85 Graves’ disease specimens. The and thyroperoxidase autoantibodies in patients with various thyroid and
clinical diagnosis was based on the criteria of the respective laboratory. The autoimmune diseases. J Clin Endocrinol Metab 1994;79(5):1404-9.
presence of autoantibodies against thyroglobulin and/or TPO was not 15. Scherbaum WA. On the clinical importance of thyroid microsomal and
necessarily a diagnostic criterion of these Graves’ disease and Hashimoto’s thyroglobulin antibody determination. Acta Endocrinol (Copenh)
thyroiditis specimens. Data from this study are summarized in the following 1987;S281:325-9.
table.* 16. Walker DJ, Griffiths M, Griffiths ID. Occurence of autoimmune diseases
and autoantibodies in multicase rheumatoid arthritis families. Ann Rheum
Hashimoto’s Thyroiditis Graves’ Disease
Dis 1986;45:323-6.
n % Positive n % Positive
17. Feldt-Rasmussen U, Rasmussen K. Serum thyroglobulin (Tg) in
68 75.0 85 75.3 presence of thyroglobulin autoantibodies (TgAb). Clinical and
* Representative data; results in individual laboratories may vary from these methodological relevance of the interaction between Tg and TgAb in
data. vitro and in vivo. J Endocrinol Invest 1985;8:571-6.
18. Schaadt B, Feldt-Rasmussen U, Rasmusson B, et al. Assessment of
High Dose Hook the influence of thyroglobulin (Tg) autoantibodies and other interfering
High dose hook is a phenomenon whereby very high level specimens may factors on the use of serum Tg as tumor marker in differentiated thyroid
falsely read within the dynamic range of the assay. For the ARCHITECT Anti- carcinoma. Thyroid 1995;5(3):165-70.
Tg, no high dose hook effect was observed when samples containing up to 19. Ericsson U-B, Christensen SB, Thorell JI. A high prevalence of
approximately 100,000 IU/mL of Anti-Tg antibody were assayed. thyroglobulin autoantibodies in adults with and without thyroid disease
as measured with a sensitive solid-phase immunosorbent radioassay.
Concordance
Clin Immunol Immunopathol 1985;37:154-62.
The performance of the ARCHITECT Anti-Tg was compared to a commercially 20. Weetman AP and McGregor AM. Autoimmune thyroid disease: further
available immunoassay for the determination of anti-Tg. A total of 234 developments in our understanding. Endocrine Reviews 1994;15(6):
specimens were evaluated in a study, encompassing a population of 788-830.
apparently healthy individuals and patients with autoimmune thyroid disease 21. US Department of Labor, Occupational Safety and Health Administration,
(Graves’ disease and Hashimoto’s thyroiditis). Specimens were tested in 29 CFR Part 1910.1030, Occupational Exposure to Bloodborne
replicates of one using the ARCHITECT Anti-Tg assay with three reagent Pathogens.
lots on three instruments and compared with a commercially available 22. 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 23. World Health Organization. Laboratory Biosafety Manual. Geneva: World
ARCHITECT Anti-Tg Negative Positive Health Organization; 2004.
24. Clinical and Laboratory Standards Institute. Protection of Laboratory
Negative 111 6
Workers from Occupationally Acquired Infections: Approved Guideline
Positive 11 106
– Third Edition. CLSI Document M29-A3. Wayne, PA: Clinical and
Concordance = 92.7% Laboratory Standards Institute, 2005.
25. Schroff RW, Foon KA, Beatty SM, et al. Human anti-murine
Sample Range (ARCHITECT) = 0.2 to 7350.6 IU/mL
immunoglobulin responses in patients receiving monoclonal antibody
Sample Range (Competitor Assay) = <1.0 to 13484.0 IU/mL
therapy. Cancer Res 1985;45:879-85.
* Representative data; results in individual laboratories may vary from these
data. 26. Primus FJ, Kelley EA, Hansen HJ, et al. “Sandwich”-type immunoassay
of carcinoembryonic antigen in patients receiving murine monoclonal
antibodies for diagnosis and therapy. Clin Chem 1988;34(2):261-4.

6
27. Boscato LM, Stuart MC. Heterophilic antibodies: a problem for all
immunoassays. Clin Chem 1988;34(1):27-33.
28. National Committee for Clinical Laboratory Standards. Evaluation of
Precision Performance of Clinical Chemistry Devices – Approved
Guideline. NCCLS document EP5-A. Wayne, PA: NCCLS, 1999.
29. National Committee for Clinical Laboratory Standards. Evaluation of
the Linearity of Quantitative Measurement Procedures: A Statistical
Approach; Approved Guideline. NCCLS document EP6-A. Wayne, PA:
NCCLS, 2003.
30. National Committee for Clinical Laboratory Standards. Interference
Testing in Clinical Chemistry: Approved Guideline. NCCLS document
EP7-A. Wayne, PA: NCCLS, 2002.

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