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.
PY - 2013/3
Y1 - 2013/3
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 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.
AB - 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.
KW - Collagen type II
KW - Post-translational modification
KW - Reactive oxygen species
KW - Rheumatoid arthritis
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U2 - 10.1007/s00125-012-2780-1
DO - 10.1007/s00125-012-2780-1
M3 - Article
C2 - 23160643
AN - SCOPUS:84878370123
VL - 56
SP - 563
EP - 572
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 3
ER -