title: The potential of multimer technologies in type 1 diabetes prediction strategies.
abstract: Type 1 diabetes is an autoimmune disease which occurs in (human leukocyte antigen) genetically predisposed individuals as a consequence of the organ-specific immune destruction of the insulin-producing β cells in the islets of Langherans within the pancreas. Type 1 diabetes is the result of a breakdown in immune regulation that leads to expansion of autoreactive CD4+ and CD8+ T cells, autoantibody-producing B lymphocytes and activation of the innate immune system. Islet-related autoantibodies revealed themselves to be good predictors of future onset of the disease, although they are not directly pathogenetic; T cells instead play a dominant role in disease initiation and progression. In this review, we first discuss the approaches that several laboratories attempted to measure human islet autoantigen-specific T-cell function in type 1 diabetes. T-cell assays could be used in combination with standardized autoantibody screenings to improve predictive strategies. They could also help to monitor in long-term follow-up the efficacy of tolerogenic immunotherapeutic strategies when established at the onset of the disease, and help to predict the recurrence of disease. Although some recent developments based on enzyme-linked immunosorbent spot and immunoblotting techniques have been able to distinguish with good sensitivity and specificity patients from controls, T-cell results, as revealed by international workshops, were indeed largely inconclusive. Nowadays, novel technologies have been exploited that could contribute to answering the tantalizing question of identifying autoreactive T cells. We particularly focus on and discuss MHC multimer tools and emphasize the advantages they can offer but also their weaknesses when used in combination with other T-cell assays. Copyright © 2011 John Wiley & Sons, Ltd.
authors.affiliation: Research Laboratories, Ospedale Pediatrico Bambino Gesù, Research Institute (IRCCS), Piazza S. Onofrio 4, Rome, Italy. fierabracci@opbg.net
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D055503:Protein Multimerization; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006680:HLA Antigens