A1 Refereed original research article in a scientific journal

Autoantibodies to N-Terminally Truncated GAD65(96-585): HLA Associations and Predictive Value for Type 1 Diabetes




AuthorsPöllänen Petra M, Härkönen Taina, Ilonen Jorma, Toppari Jorma, Veijola Riitta, Siljander Heli, Knip Mikael

PublisherOxford Academic

Publication year2022

JournalJournal of Clinical Endocrinology and Metabolism

Journal name in sourceThe Journal of clinical endocrinology and metabolism

Journal acronymJ Clin Endocrinol Metab

Volume107

Issue3

First page 935

Last page946

ISSN0021-972X

eISSN1945-7197

DOIhttps://doi.org/10.1210/clinem/dgab816

Web address https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab816/6423226?login=true

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/69176954


Abstract

Objective

To evaluate the role of autoantibodies to N-terminally truncated glutamic acid decarboxylase GAD65(96-585) (t-GADA) as a marker for type 1 diabetes (T1D) and to assess the potential HLA-associations with such autoantibodies.

Design

In this cross-sectional study combining data from the Finnish Pediatric Diabetes Register, the Type 1 Diabetes Prediction and Prevention (DIPP) Study, the DIABIMMUNE Study, and the Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity (EDIA) Study, venous blood samples from 760 individuals (53.7% males) were analyzed for t-GADA, autoantibodies to full-length GAD65 (f-GADA), and islet cell antibodies. Epitope-specific GAD autoantibodies were analyzed from 189 study participants.

Results

T1D had been diagnosed in 174 (23%) participants. Altogether 631 (83%) individuals tested positive for f-GADA and 451 (59%) for t-GADA at a median age of 9.0 years (range 0.2-61.5). t-GADA demonstrated higher specificity (46%) and positive predictive value (30%) for T1D than positivity for f-GADA alone (15% and 21%, respectively). Among participants positive for f-GADA, those who tested positive for t-GADA carried more frequently HLA genotypes conferring increased risk for T1D than those who tested negative for t-GADA (77 vs. 53%; P<0.001).

Conclusions

Autoantibodies to N-terminally truncated GAD improve the screening for T1D compared to f-GADA and may facilitate the selection of participants for clinical trials. HLA class II-mediated antigen presentation of GAD(96-585)-derived or structurally similar peptides might comprise an important pathomechanism in T1D.


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Last updated on 2024-26-11 at 18:37