HLA-haplotypes, anti- beta-cell antibodies: their role in prognostication of type 1 diabetes mellitus (results of 11-year observation)

Abstract

The risk of type 1 diabetes mellitus (DM1) depends in the first place on the presence of predetermining HLA DR haplotypes, DQ genes, and specific autoantibodies.Aim. Prospective observation of DM1 risk groups (healthy sibs of DM patients) for the elucidation of the role of genetic and autoimmune abnormalities in thedevelopment of DM1. Materials and methods. Predetermining and protective haplotypes (HLA-DRBI, DQ genes) in combination with immunological markers (autoantibodiesto cytoplasmic structures of betbeta-cells (ICA), anti-insulin autoantibodies (IAA), anti-glutamate decarboxylase autoantibodies (GAD)) were studied in healthysibs of mean age 11.9?5.8 years selected from 143 discordant families of patients with DM1. In addition, a random sample of 599 DM1 patients (mean age7.5?6.2 years) was enrolled for molecular genetic studies (HLA-DRBI-DG genes). The control group comprised 200 subjects. Results. DQAI*0501-DQB1+0201 (DQ2) and DQAI*0301-DQBI*0302 (DG8) haplotype heterozygosity creating the highest risk of DM1, the healthy sibswere divided into 3 risk groups. The high risk group 1 (DQ2/DQ8) included 23 (13.5%) subjects, moderate risk group 2 (DQ2/X, DQ8/X) 85 (59.7%), andlow risk group 3 (X/X; X - any haplotype besides DQ2, DQ8) 63 (36.8%). The frequency of autoantibodies (AB) of 2 or 3 species in group 1 was higher thanin groups 2 and 3 (26.1, 14.1, 11.1% respectively, p>0.05; 8.7, 2.4, 0%, p

Keywords

• diabetes mellitus
• hla-haplotypes
• autoantibodies
• prognostication