Identification of endothelial cell membrane proteins that bind anti-DNA antibodies from patients with systemic lupus erythematosus by direct or indirect mechanisms.

Abstract:

:A subgroup of murine monoclonal anti-DNA antibodies bind to vascular endothelial cells either directly as a result of cross-reactivity, or indirectly through immunoglobulin-bound DNA and DNA-binding proteins on the endothelial cell membrane. To determine whether these mechanisms apply in human systemic lupus erythematosus (SLE), and to identify endothelial cell membrane protein(s) that bind human anti-DNA antibodies, we examined, by Western blotting, the binding of human polyclonal anti-DNA antibodies (PoAb) isolated from eight patients with SLE to human umbilical vein endothelial cell membrane proteins. PoAbs bind to endothelial membrane proteins with Mr 84,000 and 46,000, which correspond to the DNA-binding proteins previously reported. Such binding is diminished after removal of DNA by DNase treatment. In addition, PoAbs bind to membrane proteins with Mr 180, 000, 110,000, 68,000, 44,000, and 35,000-30,000. Such binding is unaffected by alterations in DNA concentration. Anti-dsDNA and anti-ssDNA PoAbs from individual patients exhibit identical binding patterns, as are PoAbs isolated during active disease or remission. The results show that human anti-DNA antibodies can bind to endothelial cells both indirectly via immunoglobulin-bound DNA, and directly due to cross-reactivity. These mechanisms of cellular binding by anti-DNA antibodies may depict patho-genetic steps in human SLE.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Chan TM,Cheng IK

doi

10.1006/jaut.1997.9998

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

433-9

issue

5

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(97)99998-4

journal_volume

10

pub_type

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