Impaired Primary Immune Response in Type-1 Diabetes: Results from a Controlled Vaccination Study

Patients with diabetes have an increased risk for infections, but information on their adoptive immunity is incomplete and contradictory. Twenty patients with diabetes type-1 and 20 patients with type-2 diabetes were vaccinated with T-cell-dependent primary protein antigens (hepatitis A viral antigen, HAV; diphtheria toxoid) and a T-cell-independent polysaccharide antigen (pneumococcal polysaccharide). In parallel, the proliferative response of CD4+ T-cells to the primary protein antigens keyhole limpet hemocyanin (KLH) and sperm whale myoglobin (SWM) was measured in vitro using monocyte-derived dendritic cells (MDDC) as antigen-presenting cells. Compared to healthy controls, type-1 diabetes patients mounted a significantly impaired primary antibody response to hepatitis A vaccine (median HAV antibody titer after the first vaccination, 53 IU/L in diabetic patients vs 212 IU/L in the controls, P = 0.017) and diphtheria toxoid (median serum antibodies after vaccination, patients, 0.94 IU/ml, controls, 6.38 IU/ml, P = 0.004), while the response to pneumococcal polysaccharide was normal. Type-2 diabetes patients had a comparable metabolic dysregulation but showed a normal antibody response following vaccination, demonstrating that the effect was not due to hyperglycemia. Antigen-induced interferon-γ and interleukin-13 release was reduced in type-1 diabetes patients, localizing the impairment to the level of antigen-presenting cell–T-cell interaction. In addition, the proliferative response of CD4+ T-cells derived from type-1 diabetes patients to KLH and SWM was significantly reduced (P ≤ 0.01). FACS analysis of CD80 (B7.1), CD86 (B7.2), and HLA-DR expression on MDDC could not demonstrate significant differences in the expression of these molecules between type-1 and type-2 diabetes patients and healthy controls. An association of low HAV antibody response with HLA-DR3,4 expression in the patients was shown. Our results indicate that the primary antibody response to T-cell dependent antigens as well as the T-cell response to primary protein antigens is reduced in type-1 diabetes patients and that additional booster immunization can overcome the defect.