Petra M Pöllänen, Taina Härkönen, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Heli Siljander, Mikael Knip, Autoantibodies to N-terminally Truncated GAD65(96-585): HLA Associations and Predictive Value for Type 1 Diabetes, The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 3, March 2022, Pages e935–e946, https://doi.org/10.1210/clinem/dgab816
Autoantibodies to N-terminally truncated GAD₆₅(96‐585) : HLA associations and predictive value for type 1 diabetes
|Author:||Pöllänen, Petra M.1,2; Härkönen, Taina1,2; Ilonen, Jorma3;|
1Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Immunogenetic Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
4Department of Pediatrics, Turku University Hospital, and Institute of Biomedicine and Centre for Population Health Research, University of Turku, Turku, Finland
5Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
6Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
|Online Access:||PDF Full Text (PDF, 0.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022051335113
|Publish Date:|| 2022-05-13
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 human leukocyte antigen (HLA) associations with such autoantibodies.
Methods: In this cross-sectional study combining data from the Finnish Pediatric Diabetes Register, the Type 1 Diabetes Prediction and Prevention study, the DIABIMMUNE study, and the Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity 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 (range 0.2‐61.5) years. 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.
Journal of clinical endocrinology & metabolism
|Pages:||e935 - e946|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
This work was supported by the following grants: Juvenile Diabetes Research Foundation (grants 1-SRA-2016-342-M-R, 1-SRA-2019-732-M-B); European Union (grant BMH4-CT98-3314 and FP7/2007-2013 grant 202063); Novo Nordisk Foundation; Academy of Finland (Decision No 292538) and Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017 (Decision No. 250114); Special Research Funds for University Hospitals in Finland; Diabetes Research Foundation, Finland; Sigrid Jusélius Foundation, Finland; Finska Läkaresällskapet, Finland; Biomedicum Helsinki Foundation, Finland; Orion Research Foundation sr, Finland; Pediatric Research Foundation, Finland; and Yrjö Jahnsson Foundation, Finland.
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.