title: In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells.
abstract: Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients'sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients' sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.
authors.affiliation: Department of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bason
authors.forename: Renata
authors.initials: R
authors.lastname: Lorini
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.forename: Marzia
authors.initials: M
authors.lastname: Dolcino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giannattasio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: d'Annunzio
authors.forename: Antonella
authors.initials: A
authors.lastname: Rigo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pedemonte
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Antonio
authors.initials: A
authors.lastname: Puccetti
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D004770:Enterovirus / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007223:Infant; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D014764:Viral Proteins