Immunoglobulin G-Insulin Antibodies and Immune Region-Associated Alloantigens in Insulin-Dependent Diabetes Mellitus

Abstract

The importance of immune region-associated alloantigens for susceptibility to insulin-dependent diabetes (IDD), their possible influence on immunoglobulin [Ig] G-insulin antibody formation and their clinical significance were determined. Incidence of DRw3 and DRw4 (HLA D-related immune region-associated alloantigens) was found with significantly increased frequency in the IDD patients (n [number of persons] = 50) compared to healthy individuals (n = 107). Subjects positive for DRw3 carry a 4.5-fold increased risk and those positive for DRw4 carry a 2.5-fold increased risk of developing IDD. By analyzing Ig G-insulin antibody titers in DRw3-positive and DRw3-negative patients (all treated with conventional Lente [long acting] insulin), a significant tendency for high insulin-binding capacity (IBC) was noted in the latter group, yielding a mean IBC of 2.24 in DRw3-negative and 0.74 in DRw3-positive diabetics (P < 0.02). A significantly increased insulin dosage was needed for adequate metabolic control in those patients with high IBC (IBC > 3.0 U[units]/liter). Patients with high IBC and high insulin requirements were predominantly DRw3 negative. IDD is more closely associated with DRw3 than with all hitherto described HLA A, B and C locus alloantigens of the major histocompatibility complex. These immunogenetic factors seem to be of clinical importance by influencing the humoral anti-insulin immune response.