The Glutamic Acid Decarboxylase 65 Immunoglobulin G Subclass Profile Differs Between Adult-onset Type 1 Diabetes and Latent Autoimmune Diabetes in Adults (LADA) Up to 3 Years After Clinical Onset

Autoantibodies against glutamic acid decarboxylase 65 (GADA) are found frequently in patients with autoimmune diabetes. Immunoglobulin (Ig)G(1) is the most frequent subclass among the GADA IgG subclasses. IgG(4) is a more common subclass in latent autoimmune diabetes in adults (LADA) at clinical onset compared to type 1 diabetes. The aim of this work was to study the different GADA-IgG subclass profiles during a 3-year follow-up in these groups of autoimmune diabetes. Adult-onset subjects, classified as either type 1 (n = 40) or LADA (n = 43), were included in the study. New samples were collected every year from these patients. In addition to conventional GADA analyses, GADA-IgG subclasses were also analysed with a radioimmunoprecipitation assay using biotin-conjugated antibodies (directed against human IgG subclasses and IgM) and streptavidin Sepharose. During 3 years' follow-up, all the IgG subclass levels decreased in type 1 diabetes - IgG(1): P < 0.001; IgG(2): P < 0.001; IgG(3): P < 0.001; IgG(4): P < 0.05 (Friedman's' test) - while levels remained stable for all four subclasses in LADA. GADA IgM, however, decreased in both groups (P < 0.001). Patients with LADA have higher GADA IgG(3) and IgG(4) at clinical onset and seem to maintain the levels and profile of their IgG subclasses up to 3 years after clinical onset, while all the GADA IgG subclass levels decrease in type 1 diabetic patients. This indicates a persistent different immune response in LADA compared to type 1 diabetes and further indicates the difference in pathogenesis.