IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autolmmune diabetes in adults than in type 1 diabetes

Aims/hypothesis. Glutamic acid decarboxylase autoantibodies (GADA) are the most frequent beta-cell-specific autoantibodies in type I diabetes and in latent autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet cells is associated with a T helper 1 cell (T(h)1) response, mainly represented by IgG(1)-subclass in humans. It has been proposed that the presence of IgG(4) may be associated with a T(h)2 response. The aim of our study was to compare the GADA IgG-subclass distribution between adult patients with type 1 diabetes and LADA. Methods. Patients with type 1 diabetes (n=45) and patients with LADA (n=60) were included. Radioimmunoprecipitation assay with IgG-subclass specific Sepharose (IgG(1), IgG(2), IgG(3) and IgG(4)) was used to precipitate the antibody/antigen-complex. Results. We only detected IgG(4)-subclass of GADA in subjects with LADA (26.7%; p<0.001). IgG(1) was the most common GADA-subclass in both groups, however IgG(1) as the solely expressed subclass was more common among type 1 diabetic patients (77.8%; p<0.05). The rank order of the frequencies of IgG-subclasses in type I diabetes was IgG(1)>IgG(3)>IgG(2)>IgG(4) and in LADA patients IgG(1)>IgG(4)>IgG(2)>IgG(3) Conclusions/interpretation. The difference in GADA IgG-subclasses could indicate a different immune response, possibly an altered balance between TO and Th2 cytokine profile in pancreatic islets. This difference could contribute to the slower rate of beta cell destruction in LADA patients, as reflected by a higher C-peptide level at clinical onset.