title: Identification of insulin autoantibodies of IgA isotype that preferentially target non-human insulin.
abstract: Insulin autoantibodies (IAA) precede clinical type 1 diabetes in children. Immunization events leading to IAA are unknown. The aim of this study was to determine whether some IAA result from mucosal immunization. IgA-IAA and binding of IAA to non-human insulin were examined in selected high and low affinity IAA-positive samples and in first IAA-positive samples from children aged <2 years. High affinity IAA (>10(9)L/mol) bound strongly to human insulin and poorly to chicken insulin. In contrast, 12/13 lower affinity IAA were chicken insulin-reactive, binding equally to human and chicken insulin (n=4), or preferentially binding chicken insulin (n=8). IgA-IAA were found in association with chicken insulin-reactive IAA, and included cases where IgA-IAA predominated over IgG-IAA. Among 20 IAA-positive children aged <2 years, one had early IgA-chicken insulin-reactive IAA that were replaced by high affinity IgG-IAA. The findings suggest that some IAA can result from immunization against molecules other than human insulin at mucosal sites.
authors.affiliation: Diabetes Research Institute, Munich, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Koczwara
authors.forename: Daniela
authors.initials: D
authors.lastname: Muller
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D000293:Adolescent; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D001667:Binding, Competitive; D002645:Chickens; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003429:Cross Reactions / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007328:Insulin / Q000737:chemistry / Q000276:immunology*; D007330:Insulin Antibodies / Q000032:analysis* / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies