ICA+ Relatives with DQA10102/DQB10602 have Expected 0602 Sequence and DR Types

• Published in: Journal of autoimmunity Vol. 18; no. 1; pp. 67 - 70
• Main Authors: Greenbaum, Carla J., Gaur, Lakshmi K., Noble, Janelle A.
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.02.2002; Elsevier
• Subjects: Alleles; antibody positive relative, DQA10102/DQB10602, genetics, type 1 diabetes; Autoantibodies - biosynthesis; Biological and medical sciences; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Follow-Up Studies; Genes, MHC Class II - genetics; Genetic Testing; Haplotypes - genetics; histocompatibility antigen HLA; Histocompatibility Testing; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; HLA-DR Antigens - genetics; Humans; Islets of Langerhans - immunology; Medical sciences; Prospective Studies; antibody positive relative, DQA10102/DQB10602, genetics, type 1 diabetes; Endocrinopathy; Autoimmunity; Human; Immunopathology; HLA-System; Antibody; Major histocompatibility system; Class II histocompatibility antigen; Langerhans islet; Autoantibody; Autoimmune disease; HLA-DR-Locus; HLA-DQ-Locus; Insulin dependent diabetes; Genetics; Pancreas; Haplotype
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.2001.0562

The HLA haplotype DQA1*0102/DQB1*0602 reportely confers protection from type 1 diabetes. DQA1*0102/DQB1*0602 is present in more than 7% of ICA positive relatives screened as part of the Diabetes Prevention Trial— type 1. The presence of autoantibodies in these subjects suggests that the mechanism that protects DQB1*0602 subjects from diabetes occurs after the disease process has been initiated. However, as previously suggested, the method used to type the DQB1*0602 alleles may have lacked the sensitivity to identify alleles similar, but not identical, to DQB1*0602. In addition unusual extended haplotypes may be presented that could help account for the presence of diabetes autoantibodies. We therefore sequenced and performed extended haplotyping on samples from ICA+ relatives with DQA1*0102/DQB1*0602. In this group, sequencing confirmed DQB1*0602 in 149/150, and 152/165 have the common DRB1*1501-DQB1*0602 haplotype. Thus, high resolution typing of class II alleles either by PCR-based oligotyping or nucleotide sequencing fail to indicate any unusual genetic characteristics about these antibody-positive relatives, of which few are expected to progress to clinical disease.