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HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus.
Diabetologia. 2013 Mar; 56(3):563-72.D

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 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.

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Strollo R
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.
Rizzo P
No affiliation info available
Spoletini M
No affiliation info available
Landy R
No affiliation info available
Hughes C
No affiliation info available
Ponchel F
No affiliation info available
Napoli N
No affiliation info available
Palermo A
No affiliation info available
Buzzetti R
No affiliation info available
Pozzilli P
No affiliation info available
Nissim A
No affiliation info available

MeSH

Arthritis, RheumatoidAutoantibodiesBlood GlucoseCollagen Type IIDiabetes Mellitus, Type 1Enzyme-Linked Immunosorbent AssayGenotypeHLA-DRB1 ChainsHumansOxidative StressProtein Processing, Post-TranslationalReactive Oxygen Species

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23160643

Citation

Strollo, R, et al. "HLA-dependent Autoantibodies Against Post-translationally Modified Collagen Type II in Type 1 Diabetes Mellitus." Diabetologia, vol. 56, no. 3, 2013, pp. 563-72.
Strollo R, Rizzo P, Spoletini M, et al. HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus. Diabetologia. 2013;56(3):563-72.
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), 563-72. https://doi.org/10.1007/s00125-012-2780-1
Strollo R, et al. HLA-dependent Autoantibodies Against Post-translationally Modified Collagen Type II in Type 1 Diabetes Mellitus. Diabetologia. 2013;56(3):563-72. PubMed PMID: 23160643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus. AU - Strollo,R, AU - Rizzo,P, AU - Spoletini,M, AU - Landy,R, AU - Hughes,C, AU - Ponchel,F, AU - Napoli,N, AU - Palermo,A, AU - Buzzetti,R, AU - Pozzilli,P, AU - Nissim,A, Y1 - 2012/11/19/ PY - 2012/06/16/received PY - 2012/10/26/accepted PY - 2012/11/20/entrez PY - 2012/11/20/pubmed PY - 2013/8/21/medline SP - 563 EP - 72 JF - Diabetologia JO - Diabetologia VL - 56 IS - 3 N2 - 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 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. 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. SN - 1432-0428 UR - https://www.unboundmedicine.com/medline/citation/23160643/HLA_dependent_autoantibodies_against_post_translationally_modified_collagen_type_II_in_type_1_diabetes_mellitus_ L2 - https://doi.org/10.1007/s00125-012-2780-1 DB - PRIME DP - Unbound Medicine ER -