title: Impaired primary immune response in type-1 diabetes: results from a controlled vaccination study.
abstract: 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-gamma 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 < or = 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.
authors.affiliation: Krankenanstalt Rudolfstiftung, 1. Medizinische Abteilung, Juchgasse 25, A-1030 Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Eibl
authors.forename: Martin
authors.initials: M
authors.lastname: Spatz
authors.forename: Gottfried F
authors.initials: GF
authors.lastname: Fischer
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Mayr
authors.forename: Aysen
authors.initials: A
authors.lastname: Samstag
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Wolf
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
authors.forename: Martha M
authors.initials: MM
authors.lastname: Eibl
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D004168:Diphtheria Toxoid / Q000276:immunology; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D022362:Hepatitis A Vaccines / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009211:Myoglobin / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D004168:Diphtheria Toxoid; D022362:Hepatitis A Vaccines; D009211:Myoglobin; D022242:Pneumococcal Vaccines; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin