Binding of Glycoprotein 120 and Peptides from the HIV-1 Envelope by Autoantibodies in Mice with Experimentally Induced Systemic Lupus Erythematosus and in Patients with the Disease

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Abstract
Systemic lupus erythematosus (SLE) and infection with the human immunodeficiency virus type 1 (HIV) are diseases that are characterized by immune dysregulation and autoantibody production. In this article we identify and characterize IgG antibodies from mice with SLE and SLE patients that bind HIV gp120 and HIV envelope-derived peptides. SLE can be induced in susceptible mouse strains by immunization with a human monoclonal anti-DNA antibody that bears a common idiotype designated 16/6 Id. We tested sera from various strains of mice in which experimental SLE was induced by this method, as well as from 93 patients with SLE and 31 controls (17 healthy controls, 14 patients with other autoimmune diseases) for the presence of antibodies reactive to gp120 by an ELISA. Antibodies reactive with gp120 were produced by BALB/c, C3H.SW, AKR, and DBA/2 mice, all of which were 16/6 Id immunized and had experimental SLE. C57BL/6 mice, which are resistant to induction of SLE by this method, did not produce antibodies reactive with gp120 despite 16/6 immunization. Forty-three percent of SLE patients made antibodies that bound to gp 120 at titers greater than 1:40, whereas 12% of healthy control sera (p ≤ 0.02) and 14% of patients with other autoimmune diseases contained such antibodies (p ≤ 0.05). We delineated the specificity of this antibody activity by testing for reactivity to six HIV envelope peptides. In both mice and SLE patients, sera reactive with gp120 recognized the same three envelope peptides. Removal of the anti-DNA antibodies from the sera by DNA-agarose affinity purification did not change anti-gp120 specificity. We conclude that sera from mice with experimentally induced SLE and patients with SLE produce antibodies that recognize certain epitopes defined by gp120, including specific epitopes contained in the HIV envelope. Antibodies recognizing gp120 constitute a distinct population when compared to anti-DNA antibodies. These results raise the possibility that common immune dysregulatory signals are activated after HIV infection and in the development of lupus.