title: HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus.
abstract: OBJECTIVE
  In this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA.
  
  
  METHODS
  Collagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype.
  
  
  RESULTS
  Significantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA(1c)). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients.
  
  
  CONCLUSIONS
  Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.
authors.affiliation: Bone and Joint Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Strollo
authors.forename: P
authors.initials: P
authors.lastname: Rizzo
authors.forename: M
authors.initials: M
authors.lastname: Spoletini
authors.forename: R
authors.initials: R
authors.lastname: Landy
authors.forename: C
authors.initials: C
authors.lastname: Hughes
authors.forename: F
authors.initials: F
authors.lastname: Ponchel
authors.forename: N
authors.initials: N
authors.lastname: Napoli
authors.forename: A
authors.initials: A
authors.lastname: Palermo
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
authors.forename: A
authors.initials: A
authors.lastname: Nissim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D024043:Collagen Type II / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D024043:Collagen Type II; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C527195:HLA-DRB1*04 antigen; D017382:Reactive Oxygen Species