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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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J. Immunol. 167, 2791-2797
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Glomerulonephritis Induced by Recombinant Collagen IV{alpha}3 Chain Noncollagen Domain 1 Is Not Associated with Glomerular Basement Membrane Antibody: A Potential T Cell-Mediated Mechanism.
J. Wu, J. Hicks, C.-n. Ou, D. Singleton, J. Borillo, and Y.-H. Lou (2001)
J. Immunol. 167, 2388-2395
   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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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