title: The oxidative by-product, hydroxyl radical, damaged immunoglobulin-G in patients with non-insulin dependent diabetes mellitus.
abstract: OBJECTIVE
  Free radical-mediated oxidative damage and consequent protein modifications are important mediators of cell toxicity and disease pathogenesis. Earlier investigations from our laboratory revealed an increased oxidative damage in diabetes patients and hydroxyl radicals (OH) caused an extensive damage to immunoglobulin G (IgG) and oxidatively modified IgG was found to be highly immunogenic in rabbits. Here, for the first time, we evaluated the role of hydroxyl radical-damaged IgG (OH-IgG) in non insulin dependent (Type 2) diabetes patients.
  
  
  METHODS
  IgG was isolated from normal human serum by affinity chromatography and modified by hydroxyl radicals, generated by UV irradiation of hydrogen peroxide. Type 2 diabetes patients (n = 38) were accessed by direct binding and competitive inhibition ELISAs and the results were compared to healthy age and sex matched human subjects (n = 22).
  
  
  RESULTS
  A high degree of specific binding by 31.6% of diabetes sera antibodies towards OH-IgG was observed, in comparison to its native analog (p < 0.01). Antibodies from normal human subjects showed negligible binding with either of antigens (p > 0.05).
  
  
  CONCLUSIONS
  Our results suggest that hydroxyl radicals' modification of IgG causes structural perturbations, resulting in the generations of neo-epitopes, and making it a potential immunogen. The IgG modified with hydroxyl radicals may be one of the factors for the induction of circulating type 2 diabetes autoantibodies. The OH-IgG may proves one of the best markers to determine the oxidative stress in type 2 diabetes patients (Tab. 1, Fig. 4, Ref. 44).
authors.affiliation: Department of Biochemistry, Faculty of Medicine, J. N. Medical College, A.M.U. Aligarh, India.
authors.forename: Trivendra
authors.initials: T
authors.lastname: Tripathi
authors.forename: Zafar
authors.initials: Z
authors.lastname: Rasheed
mesh_terms: D000915:Antibody Affinity; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D000939:Epitopes; D007074:Immunoglobulin G; D017665:Hydroxyl Radical