Published Online
on May 6, 2004

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

This Article Full Text (PDF) All Versions of this Article: 35/6/1299    most recent 01.STR.0000128412.59768.6ev1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Undas, A. Articles by Jakubowski, H. Search for Related Content PubMed PubMed Citation Articles by Undas, A. Articles by Jakubowski, H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB L-LYSINE Medline Plus Health Information Stroke Related Collections Pathophysiology Acute Cerebral Infarction Risk Factors for Stroke

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

This article has been cited by other articles:

				H. Jakubowski, J. Perla-Kajan, R. H. Finnell, R. M. Cabrera, H. Wang, S. Gupta, W. D. Kruger, J. P. Kraus, and D. M. Shih Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in mice FASEB J, June 1, 2009; 23(6): 1721 - 1727. [Abstract] [Full Text] [PDF]

				H. Jakubowski, G. H. J. Boers, and K. A. Strauss Mutations in cystathionine {beta}-synthase or methylenetetrahydrofolate reductase gene increase N-homocysteinylated protein levels in humans FASEB J, December 1, 2008; 22(12): 4071 - 4076. [Abstract] [Full Text] [PDF]

				K. S McCully Homocysteine, vitamins, and vascular disease prevention Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1563S - 1568S. [Abstract] [Full Text] [PDF]

				A. Undas, M. Kolarz, G. Kopec, R. Glowacki, E. Placzkiewicz-Jankowska, and W. Tracz Autoantibodies against N-homocysteinylated proteins in patients on long-term haemodialysis Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1685 - 1689. [Abstract] [Full Text] [PDF]

				G. Chwatko, G. H. J. Boers, K. A. Strauss, D. M. Shih, and H. Jakubowski Mutations in methylenetetrahydrofolate reductase or cystathionine {beta}-syntase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice FASEB J, June 1, 2007; 21(8): 1707 - 1713. [Abstract] [Full Text] [PDF]

				A. Undas and H. Jakubowski Letter by Undas and Jakubowski Regarding Article, "Relationship Between Homocysteine and Mortality in Chronic Kidney Disease" Circulation, October 17, 2006; 114(16): e547 - e547. [Full Text] [PDF]

				J. Zimny, M. Sikora, A. Guranowski, and H. Jakubowski Protective Mechanisms against Homocysteine Toxicity: THE ROLE OF BLEOMYCIN HYDROLASE J. Biol. Chem., August 11, 2006; 281(32): 22485 - 22492. [Abstract] [Full Text] [PDF]

				H. Jakubowski Pathophysiological Consequences of Homocysteine Excess J. Nutr., June 1, 2006; 136(6): 1741S - 1749S. [Abstract] [Full Text] [PDF]

				G. Chwatko and H. Jakubowski Urinary Excretion of Homocysteine-Thiolactone in Humans Clin. Chem., February 1, 2005; 51(2): 408 - 415. [Abstract] [Full Text] [PDF]