title: HLA-associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent-onset insulin-dependent diabetes mellitus.
abstract: Insulin-dependent diabetes mellitus (IDDM) is a T cell-dependent immune-mediated disease. Recently, a novel islet cell antigen (ICA69) recognized by autoantibodies was described. We tested T cell responsiveness to ICA69 in peripheral blood of patients with recent onset IDDM (n = 46), patients with long-standing IDDM (n = 44), non-diabetic age-matched, islet cell autoantibody- and glutamic acid decarboxylase (GAD)65 antibody-negative first-degree relatives of IDDM patients (n = 15) and rheumatoid arthritis patients (n = 22). T cell responsiveness was significantly higher in recent onset IDDM patients, compared to IDDM patients post-disease onset, non-diabetic first degree relatives and rheumatoid arthritis patients (p < 0.001). In responding IDDM patients a significant inverse correlation between T cell and autoantibody responsiveness to ICA69 was observed (p < 0.0005). Immunogenetic evaluation revealed an association of HLA-DR3 with T cell responsiveness to ICA69 (p < 0.02) and absence of ICA69-reactive autoantibodies (p < 0.04). The increased T cell reactivity to ICA69 in the absence of antibody reactivity at onset of IDMM is associated with an HLA class II immune response gene, and therefore suggestive of a genetically controlled selective activation of T helper subsets to a specific autoantigen in humans.
authors.affiliation: Department of Immunohaematology & Blood Bank, University Hospital, Leiden, The Netherlands.
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: G
authors.initials: G
authors.lastname: Duinkerken
authors.forename: G M
authors.initials: GM
authors.lastname: Schreuder
authors.forename: H
authors.initials: H
authors.lastname: Kolb
authors.forename: R R
authors.initials: RR
authors.lastname: de Vries
authors.forename: S
authors.initials: S
authors.lastname: Martin
mesh_terms: D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006680:HLA Antigens; C087054:ICA1 protein, human