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01.03.2013 | Article

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

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

Erschienen in: Diabetologia | Ausgabe 3/2013

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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.

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Titel: HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus
verfasst von: R. Strollo
P. Rizzo
M. Spoletini
R. Landy
C. Hughes
F. Ponchel
N. Napoli
A. Palermo
R. Buzzetti
P. Pozzilli
A. Nissim
Publikationsdatum: 01.03.2013
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 3/2013
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-012-2780-1

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