Published Online
on May 6, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on December 16, 2003
Revised on March 1, 2004
Accepted on March 10, 2004

Autoantibodies Against N-Homocysteinylated Proteins in Humans. Implications for Atherosclerosis

Anetta Undas MD, PhD; Joanna Pera MS; Mariusz acinski MS; Wiesaw Trzeciak MD, PhD; Radosaw Kamierski MD, PhD; and Hieronim Jakubowski PhD^*

From the Department of Neurology (R.K.), Department of Biochemistry & Molecular Biology (M.., W.T.), Medical Sciences University, Pozna, Poland; Institute of Bioorganic Chemistry (J.P., H.J.), Polish Academy of Sciences, Pozna, Poland; Department of Microbiology & Molecular Genetics (A.U., J.P., H.J.), UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ.

^* To whom correspondence should be addressed. E-mail: jakubows{at}umdnj.edu.

Background and Purpose--Homocysteine (Hcy)-thiolactone mediates protein N-homocysteinylation in humans. Protein N-linked Hcy comprises a major pool of Hcy in human blood, greater that the "total" Hcy pool. N-homocysteinylated proteins are structurally different, compared with native proteins, and are thus likely to be recognized as neoself antigens and induce an autoimmune response. This study was undertaken to provide evidence for anti-N-Hcy-Lys-protein antibody and to examine associations between the antibody level, Hcy, and stroke in humans.

Methods--ELISA was used to quantify anti-N-Hcy-Lys-protein antibodies in human serum.

Results--We found that autoantibodies that specifically recognize N-Hcy-Lys epitope on Hcy-containing proteins occur in humans. Serum levels of anti-N-Hcy-Lys-protein autoantibodies positively correlate with plasma total Hcy levels, but not with plasma cysteine or methionine levels. In a group of exclusively male patients with stroke, mean level of anti-N-Hcy-Lys-protein autoantibodies was 50% higher than in a group of healthy subjects.

Conclusion--These findings support a hypothesis that N-Hcy-Lys-protein is a neoself antigen, which may contribute to immune activation, an important modulator of atherogenesis.

Key words: atherosclerosis • dose-response relationship, immunologic • homocysteine • immune system • immune tolerance • proteins • stroke

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