title: Heterogeneous IgG subclass distribution of islet cell antibodies.
abstract: Islet cell antibodies (ICA)-IgG are the serological marker of type 1 diabetes, an organ-specific autoimmune disease. A proportion of patients also have thyro-gastric autoimmunity, implying a broader humoral autoreactivity in these cases. In order to determine whether this is also reflected within islet cell antibodies (ICA) we examined the ICA-IgG subclass distribution in type 1 diabetic patients with or without associated thyro-gastric autoantibodies. ICA-IgG subclasses were detected by two-step indirect immunofluorescence, using monoclonal antibodies against the four IgG subclasses, in sera from 51 patients with type 1 diabetes and detectable ICA; 31 had no other antibodies (group 1) and 20 had at least one associated thyroid and/or gastric autoantibody (group 2). Our results show that ICA are polyclonal and invariably IgG1. In 48% of patients with type 1 diabetes without associated thyro-gastric autoantibodies, ICA were restricted to IgG1 only. Conversely, only 10% of those with thyro-gastric antibodies had ICA-IgG1 only (P < 0.02), and a larger ICA-IgG subclass recruitment was observed in these patients (P = 0.002). These findings provide evidence of heterogeneity within ICA at the IgG subclass level, with a broader clonal recruitment within this specificity in individuals displaying features of multiple organ autoimmunity. These results support the hypothesis of heterogeneity within the pathogenetic process leading to type 1 diabetes.
authors.affiliation: Department of Internal Medicine, San Raffaele Hospital Scientific Institute, University of Milan, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Dozio
authors.forename: C
authors.initials: C
authors.lastname: Belloni
authors.forename: A M
authors.initials: AM
authors.lastname: Girardi
authors.forename: S
authors.initials: S
authors.lastname: Genovese
authors.forename: J C
authors.initials: JC
authors.lastname: Sodoyez
authors.forename: G F
authors.initials: GF
authors.lastname: Bottazzo
authors.forename: G
authors.initials: G
authors.lastname: Pozza
authors.forename: E
authors.initials: E
authors.lastname: Bosi
mesh_terms: D001323:Autoantibodies / Q000145:classification*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification*; D007515:Islets of Langerhans / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; C024211:islet cell antibody