Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia.

Bonifacio, E; Yu, L; Williams, AK; Eisenbarth, GS; Bingley, PJ; Marcovina, SM; Adler, K; Ziegler, AG; Mueller, PW; Schatz, DA; Krischer, JP; Steffes, MW; Akolkar, B

doi:10.1210/jc.2010-0293

2010

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Title:: Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia.
Document type:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Article
Author(s):: Bonifacio, E; Yu, L; Williams, AK; Eisenbarth, GS; Bingley, PJ; Marcovina, SM; Adler, K; Ziegler, AG; Mueller, PW; Schatz, DA; Krischer, JP; Steffes, MW; Akolkar, B
Abstract:: Autoantibodies to islet antigen-2 (IA-2A) and glutamic acid decarboxylase (GADA) are markers for diagnosis, screening, and measuring outcomes in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consortia studies. A harmonization program was established to increase comparability of results within and among these studies.Large volumes of six working calibrators were prepared from pooled sera with GADA 4.8-493 World Health Organization (WHO) units/ml and IA-2A 2-235 WHO units/ml. Harmonized assay protocols for IA-2A and GADA using (35)S-methionine-labelled in vitro transcribed and translated antigens were developed based on methods in use in three NIDDK laboratories. Antibody thresholds were defined using sera from patients with recent onset type 1 diabetes and healthy controls. To evaluate the impact of the harmonized assay protocol on concordance of IA-2A and GADA results, two laboratories retested stored TEDDY study sera using the harmonized assays.The harmonized assays gave comparable but not identical results in the three laboratories. For IA-2A, using a common threshold of 5 DK units/ml, 549 of 550 control and patient samples were concordantly scored as positive or negative, specificity was greater than 99% with sensitivity 64% in all laboratories. For GADA, using thresholds equivalent to the 97th percentile of 974 control samples in each laboratory, 1051 (97.9%) of 1074 samples were concordant. On the retested TEDDY samples, discordance decreased from 4 to 1.8% for IA-2A (n = 604 samples; P = 0.02) and from 15.4 to 2.7% for GADA (n = 515 samples; P < 0.0001).Harmonization of GADA and IA-2A is feasible using large volume working calibrators and common protocols and is an effective approach to ensure consistency in autoantibody measurements.
Journal title abbreviation:: J Clin Endocrinol Metab
Year:: 2010
Journal volume:: 95
Journal issue:: 7
Pages contribution:: 3360-7
Language:: eng
Fulltext / DOI:: doi:10.1210/jc.2010-0293
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/20444913
Print-ISSN:: 0021-972X
TUM Institution:: Klinik und Poliklinik für Kinderheilkunde und Jugendmedizin
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Kinder- und Jugendmedizin (Prof. Hauer)2010