Increase in Capillary Basement Membrane Width in Parents of Children with Type I Diabetes Mellitus: Association with HLA-DR4

Hereditary factors related to HLA antigens are known to play a role in determining risk for the development of type I diabetes. In the present investigation, asymptomatic first degree relatives of diabetic patients were investigated to determine whether any abnormalities could be associated with the HLA haplo-types. Muscle biopsies were performed to obtain measurements of the width of the capillary basement membranes in 16 type I diabetic children, 20 of their unaffected siblings, and 38 parents. Only two diabetic children had capillary basement membranes greater than 2000 Å. The mean width of the capillary basement membranes was not different in affected compared with unaffected siblings. In contrast, the capillary basement membranes in the parents were considerably larger, with 14 of the 38 parents (37%) having measurements greater than 2000 Å. Moreover, the width of the capillary basement membranes in the parents correlated with the presence of the antigen HLA-DR4. The mean capillary basement membrane width in DR4 positive parents was 2026 ± 350 Å; that of DR4 negative parents was 1642 ± 333 Å. The difference was highly significant (P < 0.001). There was no correlation of capillary basement membrane width with HLA-DR3. The results suggest that a risk factor for type I diabetes associated with HLA-DR4 was associated in parents of type I diabetic patients with an asymptomatic increase in capillary basement membrane width in the absence of any clinical evidence of diabetes. The possible role of these abnormalities in the pathogenesis of type I diabetes and of the vascular complications of the disease require further study.