University of Oulu

Mikk, M-L, Pfeiffer, S, Kiviniemi, M, et al. HLA-DR-DQ haplotypes and specificity of the initial autoantibody in islet specific autoimmunity. Pediatr Diabetes. 2020; 21: 1218– 1226. https://doi.org/10.1111/pedi.13073

HLA-DR-DQ haplotypes and specificity of the initial autoantibody in islet specific autoimmunity

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Author: Mikk, Mari-Liis1; Pfeiffer, Sophie1; Kiviniemi, Minna1;
Organizations: 1Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
2Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
3Clinical Microbiology, Turku University Hospital, Turku, Finland
4Pediatric Research Center, Children Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
5Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
6Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
7Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland
8Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
9Folkhälsan Research Center, Helsinki, Finland
10Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022030121329
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2022-03-01
Description:

Abstract

Objective: We aimed to clarify the association of various HLA risk alleles with different types of autoantibodies initiating islet specific autoimmunity.

Methods: Follow-up cohorts from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and children diagnosed with type 1 diabetes (T1D) from the Finnish Pediatric Diabetes Register (FPDR) were analyzed for the presence of autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A); and genotyped for HLA DR/DQ alleles. In the DIPP study, autoantibodies were regularly analyzed from birth up to 15 years of age.

Results: In the DIPP cohort, 621 children developed one single persistent autoantibody, GADA in 284, IAA in 268, and IA-2A in 40 cases. Highly significant differences in the specificity of the first autoantibody were observed between HLA genotypes. Homozygotes for the DR3-DQ2 haplotype had almost exclusively GADA as the first autoantibody, whereas a more even distribution between GADA and IAA was found in DR3-DQ2/DR4-DQ8 as well as DR3-DQ/x and DR4-DQ8/x genotypes (x referring to neutral haplotypes). In DR4-DQ8 positive genotypes with the DRB1*04:01 allele IAA was more often the first autoantibody than in DRB1*04:04 positive genotypes. Various neutral haplotypes also significantly affected the relative proportions of different initial autoantibodies. These findings were confirmed and expanded in a series of 1591 T1D children under the age of 10 years from FPDR.

Conclusions: These results emphasize the importance of HLA class II polymorphisms in the recognition of autoantigen epitopes in the initiation of various pathways of the autoimmune response.

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Series: Pediatric diabetes
ISSN: 1399-543X
ISSN-E: 1399-5448
ISSN-L: 1399-543X
Volume: 21
Issue: 7
Pages: 1218 - 1226
DOI: 10.1111/pedi.13073
OADOI: https://oadoi.org/10.1111/pedi.13073
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3123 Gynaecology and paediatrics
Subjects:
Funding: The study was supported by the Academy of Finland (Decision No. 286765) the Sigrid Jusélius Foundation and JDRF.
Copyright information: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Mikk, M-L, Pfeiffer, S, Kiviniemi, M, et al. HLA-DR-DQ haplotypes and specificity of the initial autoantibody in islet specific autoimmunity. Pediatr Diabetes. 2020; 21: 1218– 1226, which has been published in final form at https://doi.org/10.1111/pedi.13073. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.