© 1996 American Heart Association, Inc.
Articles |
Isolation and Characterization of Human Antioxidized LDL Autoantibodies
From the Department of Microbiology and Immunology (G.V.) and Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine (M.M., M.F.L.-V.), Medical University of South Carolina, and Ralph H. Johnson VA Medical Center (M.F.L.-V.), Charleston, SC.
Correspondence to Dr Maria F. Lopes-Virella, Ralph H. Johnson VA Medical Center, 109 Bee St, Charleston, SC 29401.
Abstract Autoantibodies to oxidized LDL have been
reported in normal subjects and in patients with
arteriosclerosis, but their possible pathogenic
role is not yet well defined. One important problem is the existence of
contradictory data reported by different groups concerning the
associations between antioxidized LDL autoantibodies and the presence
or progression of arteriosclerotic lesions. Such
contradictions led us to decide to isolate and characterize
antioxidized LDL antibodies by affinity chromatography
with the use of oxidized LDL cross-linked to Sepharose.
Antioxidized LDL antibodies were isolated from selected serum samples
obtained from eight subjects. Seven of them (six patients and one
control subject) had high levels of antioxidized LDL antibody during
screening. The other subject, a healthy volunteer, had a low level of
antibody. All purified antibodies contained IgG (of subclasses 1 and 3)
as the predominant isotype and were primarily specific for oxidized LDL
but showed some cross-reactivity with malondialdehyde-modified
LDL and native LDL. Two of the purified antibodies cross-reacted
with cardiolipin. We determined average dissociation constants for the
antioxidized LDL antibodies purified from five individuals, which
varied between 2.4x10-7 and
7.5x10-7 mol/L, whereas the average
dissociation constant of rabbit hyperimmune anti-LDL antibody was
determined to be 2.7x10-8 mol/L. In
conclusion, we have purified human autoantibodies reactive with
oxidized LDL that appear to be predominantly of moderate-to-low
affinity and of variable cross-reactivity. The predominance of
IgG1 and IgG3 antibodies is significant from the standpoint of
potential pathogenicity, since these two subclasses activate
the classic complement pathway system and have the highest binding
affinities for Fc
receptors on phagocytic cells.
Key Words: autoimmunity • antioxidized LDL autoantibody isolation • arteriosclerosis • affinity constants • isotypes
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