Clinical Chemistry and Laboratory Medicine (CCLM)
Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)
Editor-in-Chief: Plebani, Mario
Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.
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Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
Citation Information: Clinical Chemical Laboratory Medicine. Volume 43, Issue 10, Pages 1011–1014, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.177, September 2005
- Published Online:
Metabolic conversion of homocysteine (Hcy) to a chemically reactive metabolite, Hcy-thiolactone, catalyzed by methionyl-tRNA synthetase is the first step in a pathway that is suggested to contribute to Hcy toxicity in humans. The accumulation of Hcy-thiolactone is detrimental because of its intrinsic ability to modify proteins by forming N-Hcy-protein adducts, in which a carboxyl group of Hcy is N-linked to the ε-amino group of a protein lysine residue. N-linked Hcy occurs in each protein examined and constitutes a significant pool of Hcy in the blood. N-Hcy proteins are likely to be recognized as neo-self antigens and induce an autoimmune response. Indeed, we found that autoantibodies specific for an Nε-Hcy-Lys epitope on N-Hcy-proteins occur in humans. Serum levels of anti-N-Hcy-protein autoantibodies are directly correlated with plasma tHcy, but not with plasma cysteine or methionine levels. In a group of male patients with stroke, levels of anti-N-Hcy-protein autoantibodies and tHcy were significantly higher than in a group of healthy subjects. In a group of male patients with angiographically documented coronary artery disease, seropositivity for anti-N-Hcy-protein autoantibodies occurred five-fold more frequently than in controls and was an independent predictor of coronary artery disease. These findings show that the formation of N-Hcy-proteins has important physiological consequences and support a hypothesis that N-Hcy-protein is a neo-self antigen that contributes to immune activation, an important modulator of atherogenesis.
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