IgG1 subclass dominates autoimmune response to tyrosine phosphatase-like molecule IA-2 in Chinese type 1 diabetes patients

Background and Aims: Islet autoantibodies are known markers for type 1 diabetes with an immune-mediated basis; their isotype or subclass profiles may also provide clues to changes in immune response during disease or after intervention. For ICAs and GADab, the IgG1 subclass consistently dominates in recent-onset disease. The aims of our study were to determine the isotype patterns for 1A-2ab in Asian Chinese patients with autoimmune diabetes. Materials and Methods: From an initial screening of over 400 diabetes patients, 40 subjects (mean age 22.2 ′ 15.8 years) with 1A-2ab were enrolled for this study. 1A-2ab was detected by radioimmunoassay of [ 3 5 S]-labelled recombinant human IA-2 i c ( 6 0 5 - 9 7 9 ) . Of them, 31 (median age 15 years, range 2-57 years; 16 children) had clinical type 1 diabetes (that is, they required insulin at onset or within 1 year) with the majority having been recently diagnosed ( 3 >2 >4; 15 subjects had detectable 1gG4-IA-2ab. Clonality of immune response determined with kappa/lambda chain-specific antibodies also showed a non-restricted pattern. Patients aged 38.2 ′ 15.2 years with type 2 diabetes had broad patterns of isotypes - IgG1/3 was detected more frequently (n = 8) than IgG2/4 (n = 5). Of three patients on insulin treatment, one was also positive for GADab. The remaining 6 patients were on oral hypoglycaemic treatment. IA-2ab in type 2 diabetes showed a low titre compared to type 1 diabetes. Conclusions: Isotype responses to IA-2 had a strong IgG1 presence, similar to ICAs and GADab. With IgG3 subclass representation, a predominant Th1 milieu in the systemic environment is likely. There is no suggestion of differences in immune response to IA-2 between adults and children with type 1 diabetes.