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The present study was undertaken to determine the importance of immune region-associated alloantigens for susceptibility to insulin-dependent diabetes (IDD), their possible influence on immunoglobulin G-insulin antibody formation, and their clinical significance. Incidence of DRw3 and DRw4 (HLA D-related immune region-associated alloantigens; w, defined by sera dispensed during the Seventh International Histocompatibility Workshop) was found with significantly increased frequency in the IDD patients (n = 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 immunoglobulin G-insulin antibody titers in DRw3-positive and DRw3-negative patients (all treated with conventional Lente 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 less than 0.02). A significantly increased insulin dosage was needed for adequate metabolic control in those patients with high IBC (IBC greater than 3.0 U/liter). Patients with high IBC and high insulin requirements were predominantly found to be DRw3 negative. Our data demonstrate that IDD is more closely associated with DRw3 than with all hitherto described HLA A, B, and C locus alloantigens of the major histocompatibility complex. In addition, these immunogenetic factors seem to be of clinical importance by influencing the humoral antiinsulin immune response.

SummaryVarious immunological parameters were determined in 46 patients with severe hemophilia A and in 9 patients with severe hemophilia B. All patients were treated over many years with commercial factor VIII or IX concentrates. Patients with severe classic hemophilia had a significantly reduced relative and absolute number of T-helper cells and a significantly increased relative and absolute number of T-suppressor cells. About half of these patients had an inverse T-helper/suppressor cell ratio. Patients with moderate hemophilia A and severe hemophilia B did not show these abnormalities. Hemophiliacs with an inverse ratio had a significantly higher concentration of serum total protein, IgG and IgM. No relationship between the amount of factor VIII concentrate administered, the HLA-type of the patient, the presence or absence of CMV-antibodies, hepatitis markers, thrombocytopenia and abnormal liver function tests to the T-cell abnormalities could be established. Lymphadenopathy was frequently associated with an inverse ratio. Indirect evidence suggests that the alterations of the immune system began in 1979/80.