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

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 gp120 at titers greater than 1:40, whereas 12% of healthy control sera (p < or = 0.02) and 14% of patients with other autoimmune diseases contained such antibodies (p < or = 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.

Toward Effective HIV Vaccination

“…Most gp120-binding preimmune Abs from humans without infection display poor or no HIV neutralizing activity (13). Patients with the autoimmune disease lupus and no HIV infection produce increased amounts of Abs to the 421-433 CD4BS region (14). A single chain Fv (scFv; V L and V H domains linked by a flexible peptide) from the lupus Ab repertoire that binds the 421-433 region reversibly neutralizes genetically diverse strains of HIV (15).…”

Constitutive Production of Catalytic Antibodies to a Staphylococcus aureus Virulence Factor and Effect of Infection

“…The scFv was isolated from an antibody library generated from the lymphocytes of patients with lupus but no evident microbial disease. Lupus is an autoimmune disease permissive for the production of antibodies with specificities that are proscribed under physiological circumstances, including antibodies specific for the HIV gp120 B-SAg determinant (68,69). We cannot exclude the possibility that the autoimmune source of the library resulted in overrepresentation of anti-Efb scFv clones.…”

Phages and HIV-1: From Display to Interplay

“…Antibodies recognizing the amino acids 421–436 of the gp120 CD4BS were isolated from patients suffering from the systemic lupus erythematosus autoimmune disease [130,131]. However, whether these antibodies neutralized HIV-1 was not known, which prompted Karle et al to quantify gp120-recognizing Abs in an existing ScFv phage-displayed library from the PBMCs of lupus-suffering patients [132].…”