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

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SummaryAutoantibodies against glutamic acid decarboxylase 65 (GADA) are found frequently in patients with autoimmune diabetes. Immunoglobulin (Ig)G1 is the most frequent subclass among the GADA IgG subclasses. IgG4 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 - IgG1: P < 0·001; IgG2: P < 0·001; IgG3: P < 0·001; IgG4: 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 IgG3 and IgG4 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.

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