HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M200370-JLR200v1 44/3/487    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Virella, G. Articles by Lopes-Virella, M. F. Search for Related Content PubMed PubMed Citation Articles by Virella, G. Articles by Lopes-Virella, M. F. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 487-493, March 2003
Copyright © 2003 by Lipid Research, Inc.

Autoimmune response to advanced glycosylation end-products of human LDL

Gabriel Virella^1,*, Suzanne R. Thorpe, Nathan L. Alderson, Elias M. Stephan, Daniel Atchley^*,, Francesco Wagner^*, and Maria F. Lopes-Virella and the DCCT/EDIC Research Group²

^* Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 92425
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208
Department of Medicine, Division of Endocrinology-Metabolism-Nutrition, Medical University of South Carolina, and Ralph H. Johnson VAMC, Charleston, SC 92425

¹ To whom correspondence should be addressed. e-mail: virellag{at}musc.edu

Advanced glycosylation end-products (AGEs) are believed to play a significant role in the development of vascular complications in diabetic patients. One such product, AGE-LDL, has been shown to be immunogenic. In this report, we describe the isolation and characterization of human AGE-LDL antibodies from the sera of seven patients with Type 1 diabetes by affinity chomatography using an immobilized AGE-LDL preparation that contained primarily the AGE N(carboxymethyl)lysine (CML, 14.6 mmol/mol lysine), and smaller amounts of N(carboxyethyl)lysine (CEL, 2.7 mmol/mol lysine). The isolated antibodies were predominantly IgG of subclasses 1 and 3, and considered proinflammatory because of their ability to promote FcR-mediated phagocytosis and to activate complement. We determined dissociation constants (K_d) for the purified antibodies. The average K_d values (4.76 ± 2.52 x 10^-9 mol/l) indicated that AGE-LDL antibodies are of higher avidity than oxidized LDL antibodies measured previously (K_d = 1.53 ± 07 x 10^-8 ml/l), but of lower avidity than rabbit polyclonal LDL antibodies (K_d = 9.34 x 10^-11). Analysis of the apolipoprotein B-rich lipoproteins isolated with polyethylene glycol-precipitated antigen-antibody complexes from the same patients showed the presence of both CML and CEL, thus confirming that these two modifications are recognized by human autoantibodies.

A comparative study of the reactivity of purified AGE-LDL antibodies with CML-LDL and CML-serum albumin showed no cross-reactivity.

Abbreviations: AGE, advanced glycosylation end-product; ALE, advanced lipoxidation end-product; CEL, (carboxyethyl)lysine; CML, (carboxymethyl)lysine; EDIC, Epidemiology of Diabetes Complication; EIA, enzymoimmunoassay; IC, immune complexes; oxLDL, oxidized LDL

Supplementary key words modified lipoproteins • diabetes • immunogenicity of advanced glycosylation end-products-LDL • advanced glycosylation end-products-LDL antibodies

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. F. Saad, G. Virella, C. Chassereau, R. J. Boackle, and M. F. Lopes-Virella OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages J. Lipid Res., September 1, 2006; 47(9): 1975 - 1983. [Abstract] [Full Text] [PDF]

				E. O. Apostolov, S. V. Shah, E. Ok, and A. G. Basnakian Quantification of Carbamylated LDL in Human Sera by a New Sandwich ELISA Clin. Chem., April 1, 2005; 51(4): 719 - 728. [Abstract] [Full Text] [PDF]

				A. Undas, J. Perla, M. Lacinski, W. Trzeciak, R. Kazmierski, and H. Jakubowski Autoantibodies Against N-Homocysteinylated Proteins in Humans: Implications for Atherosclerosis Stroke, June 1, 2004; 35(6): 1299 - 1304. [Abstract] [Full Text] [PDF]

				G. Virella and M. F. Lopes-Virella Lipoprotein Autoantibodies: Measurement and Significance Clin. Vaccine Immunol., July 1, 2003; 10(4): 499 - 505. [Full Text] [PDF]