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

Systemic lupus erythematosus (SLE) and infection with the human immuno deficiency virus type 1 (HIV) are diseases that are characterized by i mmune dysregulation and autoantibody production. In this article we id entify and characterize IgG antibodies from mice with SLE and SLE pati ents that bind HIV gp120 and HIV envelope-derived peptides. SLE can be induced in susceptible mouse strains by immunization with a human mon oclonal 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 autoimmun e diseases) for the presence of antibodies reactive to gp120 by an ELI SA. Antibodies reactive with gp120 were produced by BALB/c, C3H.SW, AK R, and DBA/2 mice, all of which were 16/6 Id immunized and had experim ental SLE. C57BL/6 mice, which are resistant to induction of SLE by th is method, did not produce antibodies reactive with gp120 despite 16/6 immunization. Forty-three percent of SLE patients made antibodies tha t bound to gp120 at titers greater than 1:40, whereas 12% of healthy c ontrol sera (p less than or equal to 0.02) and 14% of patients with ot her autoimmune diseases contained such antibodies (p less than or equa l to 0.05). We delineated the specificity of this antibody activity by testing far reactivity to six HIV envelope peptides. In both mice and SLE patients, sera reactive with gp120 recognized the same three enve lope 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 pa tients with SLE produce antibodies that recognize certain epitopes def ined by gp120, including specific epitopes contained in the HIV envelo pe. 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 infec tion and in the development of lupus.