Detection of autoantibodies against reactive oxygen species modified glutamic acid decarboxylase-65 in type 1 diabetes associated complications

From the cohort of samples, serum autoantibodies from T1D retinopathic and nephropathic patients showed high recognition of ROS-GAD65 as compared to native GAD65 (N-GAD65). Uncomplicated T1D subjects also exhibited reactivity towards ROS-GAD65. However, this was found to be less as compared to the binding recorded from complicated subjects. These results were further proven by competitive ELISA estimations. The apparent association constants (AAC) indicate greater affinity of IgG from retinopathic T1D patients (1.90 × 10-6 M) followed by nephropathic (1.81 × 10-6 M) and uncomplicated (3.11 × 10-7 M) T1D patients for ROS-GAD65 compared to N-GAD65.Increased oxidative stress and blood glucose levels with extended duration of disease in complicated T1D could be responsible for the gradual formation and/or exposing cryptic epitopes on GAD65 that induce increased production of ROS-GAD65Abs. Hence regulation of ROS-GAD65Abs could offer novel tools for analysing and possibly treating T1D complications.In autoimmune diabetes the autoantibodies have always been important for clinical interest due to their potential role in screening, diagnosis, monitoring treatment of effectiveness and prognosis. The GAD65Abs are often considered to be an epiphenomenon resulting from the autoimmune destruction of the pancreatic beta cells in T1D. Previous studies suggest that they are involved in antigen processing and presentation and thus modulate the immune response [1]. Because of the high diagnostic sensitivity for autoimmune diabetes, the presence of GAD65Ab is currently used to identify subjects at high risk for the disease [2]. GAD65Abs are detected in about 60% of new-onset cases of type 1 diabetes [3], and high levels of these autoantibodies were also reported in diabetic patients with secondary complications (such as retinopathy and nephropathy), thus leading cause of blindness and renal failure [4,5]. The exact etiology behind these complications is not completely clear.In our rec