Date: 19 Nov 2012
HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus
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.
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.
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 HbA1c). 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.
Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.
P. Pozzilli and A. Nissim contributed equally to this work.
Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50:537–546PubMed
Kim WUYW, Park W, Kang YM, Kim SI, Park JH, Lee SS, Joo YS, Min JK, Hong YS, Lee SH, Park SH, Cho CS, Kim HY (2000) IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis. J Rheumatol 3:575–581
- HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus
Volume 56, Issue 3 , pp 563-572
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Collagen type II
- Post-translational modification
- Reactive oxygen species
- Rheumatoid arthritis
- Industry Sectors
- Author Affiliations
- 1. 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
- 2. Department of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
- 3. Diabetes Care Unit, Internal Medicine, Catholic University, Rome, Italy
- 4. Department of Internal Medicine and Medical Specialties, ‘Sapienza’ University of Rome, Rome, Italy
- 5. Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, London, UK
- 6. Division of Musculoskeletal disease and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
- 7. Centre for Diabetes, Queen Mary, University of London, London, UK