IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autoimmune 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 1 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_h1) response, mainly represented by IgG₁-subclass in humans. It has been proposed that the presence of IgG₄ may be associated with a T_h2 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 (IgG₁, IgG₂, IgG₃ and IgG₄) was used to precipitate the antibody/antigen-complex.Results We only detected IgG₄-subclass of GADA in subjects with LADA (26.7%; p<0.001). IgG₁ was the most common GADA-subclass in both groups, however IgG₁ 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 1 diabetes was IgG₁>IgG₃>IgG₂>IgG₄ and in LADA patients IgG₁>IgG₄>IgG₂>IgG₃.Conclusions/interpretation The difference in GADA IgG-subclasses could indicate a different immune response, possibly an altered balance between T_h1 and T_h2 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.