PuSH - Publication Server of Helmholtz Zentrum München: Detection of antibodies directed to the N-terminal region of GAD is dependent on assay format and contributes to differences in the specificity of GAD autoantibody assays for type 1 diabetes.

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Williams, A.J.* ; Lampasona, V.* ; Schlosser, M.* ; Mueller, P.W.* ; Pittman, D.L.* ; Winter, W.E.* ; Akolkar, B.* ; Wyatt, R.* ; Brigatti, C.* ; Krause, S. ; Achenbach, P.

Detection of antibodies directed to the N-terminal region of GAD is dependent on assay format and contributes to differences in the specificity of GAD autoantibody assays for type 1 diabetes.

Diabetes 64, 3239-3246 (2015)

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Open Access Green as soon as Postprint is submitted to ZB.

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Autoantibodies to glutamate decarboxylase (GADA) are sensitive markers of islet autoimmunity and type 1 diabetes. They form the basis of robust prediction models and are widely used for recruitment of subjects at high risk of type 1 diabetes to prevention trials. However GADA are also found in many individuals at low risk of diabetes progression. To identify the sources of diabetes irrelevant GADA reactivity therefore, we analyzed data from the 2009 and 2010 Diabetes Autoantibody Standardization Program GADA workshop and found that binding of healthy control sera varied according to assay type. Characterization of control sera found positive by radiobinding assay, but negative by ELISA showed that many of these sera reacted to epitopes in the N-terminal region of the molecule. This finding prompted development of an N-terminally truncated GAD65 radiolabel, (35)S-GAD65(96-585), which improved the performance of most GADA radiobinding assays (RBAs) participating in an Islet Autoantibody Standardization Program GADA substudy. These detailed workshop comparisons have identified a source of disease-irrelevant signals in GADA RBAs and suggest that N-terminally truncated GAD labels will enable more specific measurement of GADA in type 1 diabetes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Glutamic-acid Decarboxylase; Stiff-man Syndrome; Standardization Program; Insulin Autoantibodies; Proficiency Evaluation; Epitope Recognition; Islet Antigen-2; Affinity; Risk; Mellitus

ISSN (print) / ISBN 0012-1797

e-ISSN 1939-327X

Journal Diabetes

Quellenangaben Volume: 64, Issue: 9, Pages: 3239-3246

Publisher American Diabetes Association

Publishing Place Alexandria, VA.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research Type 1 (IDF)