[HLA-antigens and islet cell antibodies in type-1 diabetics of various age groups and their first-degree relatives]

Abstract

140 type 1 diabetics from Basle and vicinity were HLA-typed. 89% had HLA-haplotypes DR3, DR4, or DR3/DR4. The frequency of these antigens was significantly increased compared to normal controls. The HLA antigens DR2 and DR5 were significantly diminished in diabetics. The increase in diabetes-associated HLA antigens differed within the diabetics according to the age of diabetes manifestation. Diabetes onset before age 40 was associated with increased frequency of HLA DR4 and HLA DR3/DR4. In contrast, patients with diabetes onset after age 40 exhibited an increased prevalence of HLA DR3. The combination HLA B7/DR4 was only observed when diabetes onset was below age 20. Islet cell antibodies (ICA) were determined in 124 of the 140 type 1 diabetics. ICA were found in 40% of patients who had had diabetes for less than 2 years, but in only 21% when diabetes had lasted more than 10 years. There was no association between certain HLA haplotypes and presence of ICA. HLA antigens and the presence of ICA were also investigated in 117 first-degree relatives of the type 1 diabetics. Compared to the latter, the relatives had a significantly diminished prevalence of the HLA DR3/DR4 combination. Compared to healthy controls, these relatives had a significantly increased frequency of positive ICA (in 12% compared to 2% in nondiabetic controls). These findings demonstrate that the genetic (HLA-antigens) and immunological (ICA) background of type 1 diabetes is heterogenous. A clinical feature of the genetically determined subtypes is the age of diabetes onset.