Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype.

TLDR

Systemic lupus erythematosus is a prototypic autoimmune disease, yet no animal model has been successfully induced by DNA immunization or anti‑DNA antibodies. The authors present a murine SLE‑like model generated by immunizing C3H.SW female mice with a common human anti‑DNA idiotype (16/6) to study disease mechanisms. Mice received a primary and booster injection of the 16/6 idiotype, producing high titers of anti‑16/6 and anti‑anti‑16/6 antibodies that exhibit anti‑DNA activity. The immunized mice developed broad autoantibody reactivity (DNA, poly(I), poly(dT), RNP, Sm, SS‑A, SS‑B, cardiolipin), elevated ESR, leukopenia, proteinuria, glomerular immune complex deposition containing the 16/6 idiotype, and glomerular sclerosis.

Abstract

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.