title: Antigenic role of the adaptive immune response to d-ribose glycated LDL in diabetes, atherosclerosis and diabetes atherosclerotic patients.
abstract: OBJECTIVE
  Glycation of proteins leads to the formation of advanced glycation end products (AGEs, which have significant role in the pathophysiology of diabetes complications. d-ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the generation of AGEs. Glycation also results in the generation of free radicals causing structural modification which leads to the generation of neoantigenic epitopes. The aim of the present study was to investigate whether LDL modification results in auto-antibodies formation against its glycated conformer in diabetes and atherosclerosis patients.
  
  
  METHODS
  The binding characteristics of circulating auto-antibodies in patients against native and modified LDL were assessed. T2D (n=105), ATH (n=106) and T2D-ATH patients (n=72) were examined by direct binding ELISA as well as inhibition ELISA, compared with healthy age-matched controls (n=50). Furthermore, ketoamine moieties, HMF and carbonyl content were also estimated in these patient's and healthy subjects.
  
  
  RESULTS
  High degree of specific binding was observed by 41.91% of T2D, 54.72% of ATH and 70.83% T2D-ATH patient's sera towards d-ribose glycated LDL, in comparison to its native analog (P<0.05). Normal human sera showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. The higher concentration of HMF, ketoamine and carbonyl content was observed in patient's sera than healthy subjects.
  
  
  CONCLUSIONS
  LDL glycation results in structural perturbation causing generation of neoantigenic epitopes that are better antigens for antibodies in T2D, ATH and T2D-ATH patients where T2D-ATH subjects showed higher prevalence in auto-antibodies against ribosylated LDL.
authors.affiliation: Department of Bio-Engineering, Integral University, Lucknow, India; Department of Bio-Sciences, Integral University, Lucknow, India.
authors.forename: Firoz
authors.initials: F
authors.lastname: Akhter
authors.affiliation: Department of Bio-Sciences, Integral University, Lucknow, India.
authors.forename: M Salman
authors.initials: MS
authors.lastname: Khan
authors.affiliation: Department of Botany & Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman A
authors.initials: AA
authors.lastname: Alatar
authors.affiliation: Department of Botany & Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Faisal
authors.affiliation: Department of Bio-Sciences, Integral University, Lucknow, India. Electronic address: saheem@iul.ac.in.
authors.forename: Saheem
authors.initials: S
authors.lastname: Ahmad
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000328:Adult; D000937:Antigen-Antibody Reactions; D000975:Antioxidants / Q000378:metabolism; D050197:Atherosclerosis / Q000150:complications / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D003925:Diabetic Angiopathies / Q000150:complications / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050050:Protein Carbonylation; D000093844:Glycated Proteins
chemical_list: D000975:Antioxidants; D001323:Autoantibodies; D000939:Epitopes; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins
keywords: Atherosclerosis; Auto-antibodies; Ribosylated LDL; Type 2 diabetes; Type 2 diabetes-atherosclerosis