title: Binding characteristics and crossreactivity of insulin autoantibodies and insulin antibodies directed to three different insulin molecules.
abstract: To evaluate ex vivo/in vitro the binding and dissociation characteristics and the level of crossreactivity of insulin antibodies and insulin autoantibodies directed to three different insulin molecules (human, bovine and porcine insulin). In this study sera from 17 diabetic patients were included, who were exclusively treated with s.c. human insulin, but presenting with severe insulin antibody mediated, immunological insulin resistance (i.e., insulin antibodies, IA). In addition, we included serum from one female patient, previously diagnosed with insulin autoimmune syndrome (no exposure to exogenous insulin treatment, i.e., insulin autoantibodies, IAA). Antibody concentrations and a binding/dissociation analysis was performed by using J(125)-labelled (position: A-14) human, porcine and bovine insulin according to the protocol described recently. In the patient with insulin autoimmune syndrome (IAA) we observed total crossreactivity between human, bovine and porcine insulin. By contrast, in the group of s.c. insulin treated diabetic patients with antibody-mediated insulin resistance (IA) we detected only partial crossreactivity. In these patients, there was a significantly higher level in the inital insulin binding (P < 0.05) directed to human insulin (median: 34%, IQR: 21.0-62.0), compared to porcine (median: 29.5%, IQR: 18.3-61.0) and bovine insulin (29%, IQR: 20.3-61.5), respectively. Here, we demonstrate different binding characteristics between IAA and IA, suggesting different epitope specificities. The observation of a significantly lower insulin binding to the "natural insulin analogs" (bovine and porcine insulin) compared to human insulin in the IA-group is in support of the concept that insulin analogs are eventually less immunogenic.
authors.affiliation: II. Medical Clinic, Main-Taunus Hospitals GmbH, Academic Teaching Hospital of Frankfurt University, Kronberger Strasse 36, 65812, Bad Soden a.Ts, Germany. cjaeger@kliniken-mtk.de
authors.forename: C
authors.initials: C
authors.lastname: Jaeger
authors.forename: S
authors.initials: S
authors.lastname: Winter
authors.forename: M
authors.initials: M
authors.lastname: Eckhard
authors.forename: P
authors.initials: P
authors.lastname: Hardt
authors.forename: M D
authors.initials: MD
authors.lastname: Brendel
authors.forename: R G
authors.initials: RG
authors.lastname: Bretzel
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D002417:Cattle; D003429:Cross Reactions / Q000276:immunology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology*; D007330:Insulin Antibodies / Q000097:blood / Q000276:immunology*; D010865:Pilot Projects; D013045:Species Specificity; D013552:Swine; D013577:Syndrome
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D007330:Insulin Antibodies