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Science 13 February 1998:
Vol. 279. no. 5353, pp. 1052 - 1054
DOI: 10.1126/science.279.5353.1052
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Reports

Uncoupling of Immune Complex Formation and Kidney Damage in Autoimmune Glomerulonephritis

Raphael Clynes, Calin Dumitru, Jeffrey V. Ravetch *

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 gamma  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.

Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021, USA.
*   To whom correspondence should be addressed. E-mail: ravetch{at}rockvax.rockefeller.edu

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   Abstract »    Full Text »    PDF »
Resistance to Xenobiotic-Induced Autoimmunity Maps to Chromosome 1.
D. H. Kono, M. S. Park, A. Szydlik, K. M. Haraldsson, J. D. Kuan, D. L. Pearson, P. Hultman, and K. M. Pollard (2001)
J. Immunol. 167, 2396-2403
   Abstract »    Full Text »    PDF »
A Dominant Role for Fc{{gamma}} Receptors in Antibody-Dependent Corneal Inflammation.
L. R. Hall, E. Diaconu, and E. Pearlman (2001)
J. Immunol. 167, 919-925
   Abstract »    Full Text »    PDF »
Distinct Tissue Site-Specific Requirements of Mast Cells and Complement Components C3/C5a Receptor in IgG Immune Complex-Induced Injury of Skin and Lung.
U. Baumann, N. Chouchakova, B. Gewecke, J. Kohl, M. C. Carroll, R. E. Schmidt, and J. E. Gessner (2001)
J. Immunol. 167, 1022-1027
   Abstract »    Full Text »    PDF »
Accelerated Nephrotoxic Nephritis Is Exacerbated in C1q-Deficient Mice.
M. G. Robson, H. T. Cook, M. Botto, P. R. Taylor, N. Busso, R. Salvi, C. D. Pusey, M. J. Walport, and K. A. Davies (2001)
J. Immunol. 166, 6820-6828
   Abstract »    Full Text »    PDF »
Complement Component C3 Is Not Required for Full Expression of Immune Complex Glomerulonephritis in MRL/lpr Mice.
H. Sekine, C. M. Reilly, I. D. Molano, G. Garnier, A. Circolo, P. Ruiz, V. M. Holers, S. A. Boackle, and G. S. Gilkeson (2001)
J. Immunol. 166, 6444-6451
   Abstract »    Full Text »    PDF »
Fc{{gamma}}RIII-Mediated Production of TNF-{{alpha}} Induces Immune Complex Alveolitis Independently of CXC Chemokine Generation.
N. Chouchakova, J. Skokowa, U. Baumann, T. Tschernig, K. M. H. Philippens, B. Nieswandt, R. E. Schmidt, and J. E. Gessner (2001)
J. Immunol. 166, 5193-5200
   Abstract »    Full Text »    PDF »
Lymphocytes induce monocyte chemoattractant protein-1 production by renal cells after Fc{gamma} receptor cross-linking: role of IL-1{beta}.
B. H. Rovin, L. Lu, and C. B. Marsh (2001)
J. Leukoc. Biol. 69, 435-439
   Abstract »    Full Text »
Lyn Is Essential for Fc{{gamma}} Receptor III-mediated Systemic Anaphylaxis but Not for the Arthus Reaction.
T. Yuasa, M. Ono, T. Watanabe, and T. Takai (2001)
J. Exp. Med. 193, 563-572
   Abstract »    Full Text »    PDF »
Genetic remodeling of protein glycosylation in vivo induces autoimmune disease.
D. Chui, G. Sellakumar, R. S. Green, M. Sutton-Smith, T. McQuistan, K. W. Marek, H. R. Morris, A. Dell, and J. D. Marth (2001)
PNAS 98, 1142-1147
   Abstract »    Full Text »    PDF »
The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes.
L. Morel, K. R. Blenman, B. P. Croker, and E. K. Wakeland (2001)
PNAS
   Abstract »    Full Text »
Long-term anti-CD154 dosing in nephritic mice is required to maintain survival and inhibit mediators of renal fibrosis.
S L Kalled, A H Cutler, and J L Ferrant (2001)
Lupus 10, 9-22
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Differential Modulation of Stimulatory and Inhibitory Fc{{gamma}} Receptors on Human Monocytes by Th1 and Th2 Cytokines.
L. Pricop, P. Redecha, J.-L. Teillaud, J. Frey, W. H. Fridman, C. Sautes-Fridman, and J. E. Salmon (2001)
J. Immunol. 166, 531-537
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Markedly Different Pathogenicity of Four Immunoglobulin G Isotype-Switch Variants of an Antierythrocyte Autoantibody Is Based on Their Capacity to Interact In Vivo with the Low-Affinity Fc{gamma} Receptor III.
L. Fossati-Jimack, A. Ioan-Facsinay, L. Reininger, Y. Chicheportiche, N. Watanabe, T. Saito, F. M. A. Hofhuis, J. E. Gessner, C. Schiller, R. E. Schmidt, et al. (2000)
J. Exp. Med. 191, 1293-1302
   Abstract »    Full Text »    PDF »
Stimulation of Fc{gamma}R receptors induces monocyte chemoattractant protein-1 in the human monocytic cell line THP-1 by a mechanism involving I{kappa}B-{alpha} degradation and formation of p50/p65 NF-{kappa}B/Rel complexes.
A. Alonso, Y. Bayon, M. Renedo, and M. S. Crespo (2000)
Int. Immunol. 12, 547-554
   Abstract »    Full Text »    PDF »
Administration of IgG Fc Fragments Prevents Glomerular Injury in Experimental Immune Complex Nephritis.
C. Gomez-Guerrero, N. Duque, M. T. Casado, C. Pastor, J. Blanco, F. Mampaso, F. Vivanco, and J. Egido (2000)
J. Immunol. 164, 2092-2101
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C-Reactive Protein Binding to Murine Leukocytes Requires Fc{gamma} Receptors.
M.-P. Stein, C. Mold, and T. W. Du Clos (2000)
J. Immunol. 164, 1514-1520
   Abstract »    Full Text »    PDF »
Racial group, socioeconomic status, and the development of persistent proteinuria in systemic lupus erythematosus.
N D Hopkinson, C Jenkinson, K R Muir, M Doherty, and R J Powell (2000)
Ann Rheum Dis 59, 116-119
   Abstract »    Full Text »
Links between complement abnormalities and systemic lupus erythematosus.
M. C. Pickering and M. J. Walport (2000)
Rheumatology 39, 133-141
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A Codominant Role of Fc{gamma}RI/III and C5aR in the Reverse Arthus Reaction.
U. Baumann, J. Kohl, T. Tschernig, K. Schwerter-Strumpf, J. S. Verbeek, R. E. Schmidt, and J. E. Gessner (2000)
J. Immunol. 164, 1065-1070
   Abstract »    Full Text »    PDF »
The Arthus Reaction in Rodents: Species-Specific Requirement of Complement.
A. J. Szalai, S. B. Digerness, A. Agrawal, J. F. Kearney, R. P. Bucy, S. Niwas, J. M. Kilpatrick, Y. S. Babu, and J. E. Volanakis (2000)
J. Immunol. 164, 463-468
   Abstract »    Full Text »    PDF »
Systemic lupus erythematosus--messages from experimental models.
M. L. Stoll and J. Gavalchin (2000)
Rheumatology 39, 18-27
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