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


Journal of Nephrology & Therapeutics

Author(s): Khan MW, Banga K, Mashal SN, Khan WA

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Abstract BACKGROUND: Autoantibodies against glutamate decarboxylase-65 (GAD₆₅Abs) are thought to be a major immunological tool involved in pathogenic autoimmunity development in various diseases. GAD₆₅Abs are a sensitive and specific marker for type 1 diabetes (T1D). These autoantibodies can also be found in 6-10\% of patients classified with type 2 diabetes (T2D), as well as in 1-2\% of the healthy population. The latter individuals are at low risk of developing T1D because the prevalence rate of GAD₆₅Abs is only about 0.3\%. It has, therefore, been suggested that the antibody binding to GAD₆₅ in these three different GAD₆₅Ab-positive phenotypes differ with respect to epitope specificity. The specificity of reactive oxygen species modified GAD₆₅ (ROS-GAD₆₅) is already well established in the T1D. However, its association in secondary complications of T1D has not yet been ascertained. Hence this study focuses on identification of autoantibodies against ROS-GAD₆₅ (ROS-GAD₆₅Abs) and quantitative assays in T1D associated complications. RESULTS: 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 x 10⁻⁶ M) followed by nephropathic (1.81 x 10⁻⁶ M) and uncomplicated (3.11 x 10⁻⁷ M) T1D patients for ROS-GAD₆₅ compared to N-GAD₆₅. CONCLUSION: 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.
This article was published in BMC Immunol and referenced in Journal of Nephrology & Therapeutics

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