Coxsackie virus B antibodies are increased in HLA DR3-MICA5.1 positive type 1 diabetes patients in the Linköping region of Sweden

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which genetics and environmental factors play a role. Among the environmental factors, viruses (especially Coxsackie virus B [CBV]), and among genetic markers, human leukocyte antigen (HLA) DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) and DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2), and major histocompatibility complex class I chain-related gene-A (MICA) alleles 5 and 5.1 have been reported to be associated with T1DM in Caucasians. Sweden ranks third in the world for T1DM incidence. In Sweden, the Linköping region indicates the highest incidence for T1DM. In this study, we analyzed whether antibodies against CBV are increased in DR3, DR4, MICA5, or MICA5.1 positive patients from Linköping ( n = 46) and from Swedish population as a whole ( n = 298) between the age of 0 and 15 years old. There was no difference in the frequency of antibodies to CBV in patients compared with controls in Linköping (26% vs 23%) or in all of Sweden (26% vs 21%). However, CBV antibodies were increased in DR3, DR3-DR4 (heterozygous), DR3-MICA5.1, and DR3-DR4-MICA5.1 positive compared with DR3, DR3-DR4, DR3-MICA5.1, and DR3-DR4-MICA5.1 negative patients in Linköping ( p < 0.05 for all), but not in Swedish population as a whole. Thus, our study suggests that in addition to DR3, MICA5.1 has an influence on the immune response to CBV infection in patients from Linköping.