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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1254.)
© 2001 American Heart Association, Inc.

Editorials

The First Human Monoclonal Antibody to Oxidized LDL

Godfrey S. Getz

From the Department of Pathology, University of Chicago, Chicago, Ill.

Correspondence to Dr Godfrey S. Getz, Department of Pathology, University of Chicago, BH-329, MC 3083, 5841 S Mayfield Ave, Chicago, IL 60637-1470. E-mail g-getz@uchicago.edu

Largely as a result of the seminal observations of Steinberg and colleagues¹ on oxidized lipoproteins and the work of Witztum and his colleagues on the immunological response to these modified lipoproteins, there has been much recent interest in the significance and role of antibodies to oxidized LDL (oxLDL) in the plasma of humans and animals with evolving atherosclerosis. This interest has focused on the value of these antibodies for the diagnosis of atherosclerosis and, more important, in its pathogenesis. This story is now greatly advanced by the article from Witztum and colleagues (Shaw et al²) in this issue of the Journal, in which they report on the isolation and characterization of the first human monoclonal antibody that recognizes epitopes of oxLDL. These authors started with RNA extracted from peripheral blood mononuclear cells of a patient with coronary artery disease that were expressing high titers of antibody to malondialdehyde LDL (MDA-LDL). They used this RNA to prepare cDNA, from which they generated 2 phage (filamentous) display libraries expressing the variable chains of heavy and light immunoglobulins with both the k and l light-chain families. These libraries were screened against MDA-LDL through several rounds. Three specific IgG antibodies were isolated that bind MDA-LDL. One of these antibodies, 1K 17, was characterized in some detail with respect to its immunological and biological properties. This antibody bound to the lipid and protein moieties of oxLDL but not to native LDL. 1K 17 also recognized apoptotic cells. It inhibited the uptake of both oxLDL . . . [Full Text of this Article]