HLA-DR-DQhaplotypes and specificity of the initial autoantibody in islet specific autoimmunity
| Autor: | Taina Härkönen, Minna Kiviniemi, Jorma Toppari, Mari Liis Mikk, Jorma Ilonen, Sophie Pfeiffer, Antti Laine, Johanna Lempainen, Mikael Knip, Riitta Veijola |
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| Přispěvatelé: | Staff Services, HUS Children and Adolescents, Research Programs Unit, Children's Hospital, University of Helsinki, Helsinki University Hospital Area, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, Research Group Knip |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
type 1 diabetes Endocrinology Diabetes and Metabolism CHILDREN medicine.disease_cause DISEASE Autoimmunity A-CHAIN 0302 clinical medicine T-CELL EPITOPES Risk Factors 3123 Gynaecology and paediatrics Genotype 030212 general & internal medicine Child Finland ASSOCIATIONS RISK 3. Good health Child Preschool Female INSULIN AUTOANTIBODIES Adolescent 030209 endocrinology & metabolism HLA genotypes Human leukocyte antigen DEPENDENT DIABETES-MELLITUS 03 medical and health sciences GLUTAMIC-ACID DECARBOXYLASE HLA-DQ Antigens Internal Medicine medicine HLA-DR Humans Receptor-Like Protein Tyrosine Phosphatases Class 8 Allele Autoantibodies Type 1 diabetes business.industry Haplotype Infant Newborn Autoantibody Infant HLA-DR Antigens medicine.disease Diabetes Mellitus Type 1 Haplotypes Pediatrics Perinatology and Child Health Immunology ONSET islet specific autoantibodies business |
| Popis: | 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 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. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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