HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus

R. Strollo, P. Rizzo, M. Spoletini, R. Landy, C. Hughes, F. Ponchel, N. Napoli, A. Palermo, R. Buzzetti, P. Pozzilli, A. Nissim

Research output: Contribution to journalArticle

Abstract

Aims/hypothesis: 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 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. Conclusion: Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.

Original languageEnglish
Pages (from-to)563-572
Number of pages10
JournalDiabetologia
Volume56
Issue number3
DOIs
Publication statusPublished - Mar 2013

Keywords

  • Collagen type II
  • Post-translational modification
  • Reactive oxygen species
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Strollo, R., Rizzo, P., Spoletini, M., Landy, R., Hughes, C., Ponchel, F., Napoli, N., Palermo, A., Buzzetti, R., Pozzilli, P., & Nissim, A. (2013). HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus. Diabetologia, 56(3), 563-572. https://doi.org/10.1007/s00125-012-2780-1