Measurement of islet cell antibodies in the Type 1 Diabetes Genetics Consortium: efforts to harmonize procedures among the laboratories

Clin Trials. 2010;7(1 Suppl):S56-64. doi: 10.1177/1740774510373496.


Background: and

Purpose: Three network laboratories measured antibodies to islet autoantigens. Antibodies to glutamic acid decarboxylase (GAD65 [GADA]) and the intracellular portion of protein tyrosine phosphatase (IA-2(ic) [IA-2A]) were measured by similar, but not identical, methods in samples from participants in the Type 1 Diabetes Genetics Consortium (T1DGC).

Methods: All laboratories used radiobinding assays to detect antibodies to in vitro transcribed and translated antigen, but with different local standards, calibrated against the World Health Organization (WHO) reference reagent. Using a common method to calculate WHO units/mL, we compared results reported on samples included in the Diabetes Autoantibody Standardization Program (DASP), and developed standard methods for reporting in WHO units/mL. We evaluated intra-assay and inter-assay coefficient of variation (CV) in blind duplicate samples and assay comparability in four DASP workshops.

Results: Values were linearly related in the three laboratories for both GADA and IA-2A, and intra-assay technical errors for values within the standard curve were below 13% for GADA and below 8.5% for IA-2A. Correlations in samples tested 1-2 years apart were >97%. Over the course of the study, internal CVs were 10-20% with one exception, and the laboratories concordantly called samples GADA or IA-2A positive or negative in 96.7% and 99.6% of duplicates within the standard curve. Despite acceptable CVs and general concordance in ranking samples, the laboratories differed markedly in absolute values for GADA and IA-2A reported in WHO units/mL in DASP over a large range of values.

Limitations: With three laboratories using different assay methods (including calibrators), consistent values among them could not be attained.

Conclusions: Modifications in the assays are needed to improve comparability of results expressed as WHO units/mL across laboratories. It will be essential to retain high intra- and inter-assay precision, sensitivity and specificity and to confirm the accuracy of harmonized methods.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies / immunology*
  • Autoantigens / analysis*
  • Autoantigens / immunology
  • Clinical Laboratory Techniques / instrumentation*
  • Clinical Laboratory Techniques / standards
  • Data Collection / methods*
  • Diabetes Mellitus, Type 1 / genetics*
  • Education
  • Global Health
  • Humans
  • Internationality
  • Islets of Langerhans / immunology*
  • Quality Control
  • ROC Curve
  • Statistics as Topic


  • Antibodies
  • Autoantigens