Induction of a Systemic Lupus Erythematosus-Like Disease in Mice by a Common Human Anti-DNA Idiotype

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-04, Vol.85 (7), p.2260-2264
• Main Authors: Mendlovic, Shlomo, Brocke, Stefan, Shoenfeld, Yehuda, Ben-Bassat, Minna, Meshorer, Asher, Bakimer, Ronit, Mozes, Edna
• Format: Article
• Language: English
• Subjects: 550501 - Metabolism- Tracer Techniques; ANIMALS; ANTIBODIES; Antibodies, Antinuclear - immunology; ANTIGENS; Autoimmune diseases; Autoimmune Diseases - etiology; Autoimmune Diseases - immunology; Autoimmunity (experimental aspects and models); BACTERIAL DISEASES; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BIOASSAY; BIOCHEMISTRY; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CHEMISTRY; CYTOCHEMISTRY; DAYS LIVING RADIOISOTOPES; DIAGNOSTIC TECHNIQUES; Disease models; Disease Models, Animal; DISEASES; DNA; ELECTRON CAPTURE RADIOISOTOPES; ELECTRON MICROSCOPY; ENZYME IMMUNOASSAY; ERYTHROCYTES; Experimental autoimmune diseases; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; GLOBULINS; HEMIC DISEASES; HISTOLOGY; Humans; IMMUNE SYSTEM DISEASES; IMMUNITY; IMMUNOASSAY; Immunoglobulin Idiotypes - immunology; IMMUNOGLOBULINS; IMMUNOLOGY; INFECTIOUS DISEASES; INTERMEDIATE MASS NUCLEI; IODINE 125; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KIDNEYS; LEUKOPENIA; LUPUS; Lupus Erythematosus, Systemic - etiology; MAMMALS; MATERIALS; MICE; Mice, Inbred C3H - immunology; MICROSCOPY; MONOCLONAL ANTIBODIES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; Pathology; PROTEINS; RADIOASSAY; RADIOIMMUNOASSAY; RADIOIMMUNODETECTION; RADIOIMMUNOLOGY; RADIOISOTOPES; RODENTS; SKIN DISEASES; Systemic lupus erythematosus; TRACER TECHNIQUES; TRANSMISSION ELECTRON MICROSCOPY; TUBERCULOSIS; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.7.2260

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.