Uncoupling of Immune Complex Formation and Kidney Damage in Autoimmune Glomerulonephritis

• Published in: Science (American Association for the Advancement of Science) Vol. 279; no. 5353; pp. 1052 - 1054
• Main Authors: Clynes, Raphael, Dumitru, Calin, Ravetch, Jeffrey V.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 13-02-1998; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Antibodies, Antinuclear - blood; Antigen antibody complex; Antigen-Antibody Complex - blood; Antigen-Antibody Complex - immunology; Attrition (Research Studies); Autoantibodies; Autoimmune diseases; Biological and medical sciences; Complement Activation; Complement System Proteins - analysis; Crosses, Genetic; Disease Models, Animal; Experimental and animal immunopathology. Animal models; Feedback (Response); Genes; Genetic aspects; Genetics; Glomerular Mesangium - immunology; Glomerular Mesangium - pathology; Glomerulonephritis; Immunity; Immunology; Immunopathology; Kidney Glomerulus - immunology; Kidney Glomerulus - pathology; Kidneys; Lupus Nephritis - immunology; Lupus Nephritis - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Molecular biology; Proteins; Proteinuria; Receptors; Receptors, IgG - genetics; Receptors, IgG - immunology; Rodents; Kidney disease; Glomerulonephritis; Immunopathology; Animal model; Urinary system disease; Gamma-Peptide chain; Rodentia; Autoantibody; Autoimmune disease; Kidney; Vertebrata; Mammalia; Fc-Fragment; Gene; Mouse; Lupus erythematosus; Lesion; Mutation; Immune complex
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.279.5353.1052

The generation of autoantibody and subsequent tissue deposition of immune complexes (IC) is thought to trigger the pathogenic consequences of systemic autoimmune disease. Modulation of the autoantibody response disrupts pathogenesis by preventing the formation of ICs; however, uncoupling IC formation from subsequent inflammatory responses seems unlikely because of the apparent complexity of the IC-triggered inflammatory cascade. However, the disruption of a single gene, which encodes the γ chain of the Fc receptor, was found to achieve this uncoupling in a spontaneous model of lupus nephritis, the New Zealand Black/New Zealand White (NZB/NZW) mouse. Gamma chain-deficient NZB/NZW mice generated and deposited IC and activated complement, but were protected from severe nephritis, thus defining another potential pathway for therapeutic intervention in autoimmune disease.