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Fcγ receptors: structure, function and role as genetic risk factors in SLE

Genes & Immunity volume 10, pages 380–389 (2009)Cite this article

Abstract

Over 30 years ago, receptors for the Fc region of IgG (FcγR) were implicated in the pathogenesis of systemic lupus erythematosus (SLE). Since those pioneering studies, our knowledge of the structure and function of these FcγRs has increased dramatically. We now know that FcγR contributes to the regulation of acquired immunity and to the regulation of innate immune responses where FcγRs act as specific receptors for innate opsonins (CRP and SAP). Our understanding of the genomic architecture of the genes encoding the FcγR has also witnessed remarkable advances. Numerous functionally relevant single-nucleotide polymorphism (SNP) variants and copy number (CN) variants have been characterized in the FcγR genes. Many of these variants have also been shown to associate with risk to development of SLE and some have been associated with disease progression. This review will provide an overview of the FcγR in relation to SLE, including consideration of the role of genetic variants in FcγR in SLE pathogenesis. The difficulties in assessing genetic variation in these genes will be discussed. To enhance our understanding of the functional roles of these receptors in SLE, future research will need to integrate our knowledge of SNP variants, CN variants and the functional diversity of these receptors.

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References

  1. Sestak AL, Shaver TS, Moser KL, Neas BR, Harley JB . Familial aggregation of lupus and autoimmunity in an unusual multiplex pedigree. J Rheumatol 1999; 26: 1495–1499.

    CAS  PubMed  Google Scholar 

  2. Arnett FC, Familial SLE . The HLA System and the Genetics of Lupus Erythematosus 3rd ed Lea & Febiger: Philadelphia, 1987.

    Google Scholar 

  3. Vyse TJ, Todd JA . Genetic analysis of autoimmune disease. Cell 1996; 85: 311–318.

    Article  CAS  PubMed  Google Scholar 

  4. Buckman KJ, Moore SK, Ebbin AJ, Cox MB, Dubois EL . Familial systemic lupus erythematosus. Arch Intern Med 1978; 138: 1674–1676.

    Article  CAS  PubMed  Google Scholar 

  5. Lawrence JS, Martins CL, Drake GL . A family survey of lupus erythematosus. 1. Heritability. J Rheumatol 1987; 14: 913–921.

    CAS  PubMed  Google Scholar 

  6. Deapen D, Escalante A, Weinrib L, Horwitz D, Bachman B, Roy-Burman P et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 1992; 35: 311–318.

    Article  CAS  PubMed  Google Scholar 

  7. Block SR, Winfield JB, Lockshin MD, D'Angelo WA, Christian CL . Studies of twins with systemic lupus erythematosus. A review of the literature and presentation of 12 additional sets. Am J Med 1975; 59: 533–552.

    Article  CAS  PubMed  Google Scholar 

  8. Reichlin M, Harley JB, Lockshin MD . Serologic studies of monozygotic twins with systemic lupus erythematosus. Arthritis Rheum 1992; 35: 457–464.

    Article  CAS  PubMed  Google Scholar 

  9. Cantor RM, Yuan J, Napier S, Kono N, Grossman JM, Hahn BH et al. Systemic lupus erythematosus genome scan: support for linkage at 1q23, 2q33, 16q12–13, and 17q21–23 and novel evidence at 3p24, 10q23–24, 13q32, and 18q22–23. Arthritis Rheum 2004; 50: 3203–3210.

    Article  CAS  PubMed  Google Scholar 

  10. Johanneson B, Lima G, von Salome J, Alarcon-Segovia D, Alarcon-Riquelme ME . A major susceptibility locus for systemic lupus erythemathosus maps to chromosome 1q31. Am J Hum Genet 2002; 71: 1060–1071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N et al. Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees. Proc Natl Acad Sci USA 1998; 95: 14869–14874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Olson JM, Song Y, Dudek DM, Moser KL, Kelly JA, Bruner GR et al. A genome screen of systemic lupus erythematosus using affected-relative-pair linkage analysis with covariates demonstrates genetic heterogeneity. Genes Immun 2002; 3 (Suppl 1): S5–S12.

    Article  CAS  PubMed  Google Scholar 

  13. Shai R, Quismorio Jr FP, Li L, Kwon OJ, Morrison J, Wallace DJ et al. Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families. Hum Mol Genet 1999; 8: 639–644.

    Article  CAS  PubMed  Google Scholar 

  14. Tsao BP, Cantor RM, Kalunian KC, Chen CJ, Badsha H, Singh R et al. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. J Clin Invest 1997; 99: 725–731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tsao BP . Lupus susceptibility genes on human chromosome 1. Int Rev Immunol 2000; 19: 319–334.

    Article  CAS  PubMed  Google Scholar 

  16. Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH, Frank MM . A serial study of splenic reticuloendothelial system Fc receptor functional activity in systemic lupus erythematosus. Arthritis Rheum 1982; 25: 48–54.

    Article  CAS  PubMed  Google Scholar 

  17. Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH . Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med 1979; 300: 518–523.

    Article  CAS  PubMed  Google Scholar 

  18. Salmon JE, Kimberly RP, Gibofsky A, Fotino M . Defective mononuclear phagocyte function in systemic lupus erythematosus: dissociation of Fc receptor-ligand binding and internalization. J Immunol 1984; 133: 2525–2331.

    CAS  PubMed  Google Scholar 

  19. Nimmerjahn F, Ravetch JV . Fc-receptors as regulators of immunity. Nat Rev Immunol 2008; 8: 34–47.

    Article  CAS  PubMed  Google Scholar 

  20. Croker JA, Kimberly RP . Genetics of susceptibility and severity in systemic lupus erythematosus. Curr Opin Rheumatol 2005; 17: 529–537.

    Article  CAS  PubMed  Google Scholar 

  21. Salmon JE, Edberg JC, Brogle NL, Kimberly RP . Allelic polymorphisms of human Fc gamma receptor IIA and Fc gamma receptor IIIB. Independent mechanisms for differences in human phagocyte function. J Clin Invest 1992; 89: 1274–1281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Salmon JE, Edberg JC, Kimberly RP . Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities. J Clin Invest 1990; 85: 1287–1295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ernst LK, van de Winkel JG, Chiu IM, Anderson CL . Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI) encode four distinct transcription products. J Biol Chem 1992; 267: 15692–15700.

    Article  CAS  PubMed  Google Scholar 

  24. Hoffmeyer F, Witte K, Schmidt RE . The high-affinity Fc gamma RI on PMN: regulation of expression and signal transduction. Immunology 1997; 92: 544–552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Capel PJ, van de Winkel JG, van den Herik-Oudijk IE, Verbeek JS . Heterogeneity of human IgG Fc receptors. Immunomethods 1994; 4: 25–34.

    Article  CAS  PubMed  Google Scholar 

  26. Ernst LK, Metes D, Herberman RB, Morel PA . Allelic polymorphisms in the FcgammaRIIC gene can influence its function on normal human natural killer cells. J Mol Med 2002; 80: 248–257.

    Article  CAS  PubMed  Google Scholar 

  27. Breunis WB, van Mirre E, Bruin M, Geissler J, de Boer M, Peters M et al. Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood 2008; 111: 1029–1038.

    Article  CAS  PubMed  Google Scholar 

  28. Simmons D, Seed B . The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature 1998; 333: 568–570.

    Article  Google Scholar 

  29. Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S et al. Specificity and affinity of human Fc{gamma} receptors and their polymorphic variants for human IgG subclasses. Blood 2009; 113: 3716–3725.

    Article  CAS  PubMed  Google Scholar 

  30. Ghazizadeh S, Bolen JB, Fleit HB . Tyrosine phosphorylation and association of Syk with Fc gamma RII in monocytic THP-1 cells. Biochem J 1995; 305: 669–674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ghazizadeh S, Bolen JB, Fleit HB . Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells. J Biol Chem 1994; 269: 8878–8884.

    Article  CAS  PubMed  Google Scholar 

  32. Bezman N, Koretzky GA . Compartmentalization of ITAM and integrin signaling by adapter molecules. Immunol Rev 2007; 218: 9–28.

    Article  CAS  PubMed  Google Scholar 

  33. Odin JA, Edberg JC, Painter CJ, Kimberly RP, Unkeless JC . Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor. Science 1991; 254: 1785–1788.

    Article  CAS  PubMed  Google Scholar 

  34. Liao F, Shin HS, Rhee SG . Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. Proc Natl Acad Sci USA 1992; 89: 3659–3663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kimberly RP, Wu J, Gibson AW, Su K, Qin H, Li X et al. Diversity and duplicity: human Fcγ receptors in host defense and autoimmunity. Immunol Res 2002; 26: 177–189.

    Article  CAS  PubMed  Google Scholar 

  36. Takai T . Roles of Fc receptors in autoimmunity. Nat Rev Immunol 2002; 2: 580–592.

    Article  CAS  PubMed  Google Scholar 

  37. van Vugt MJ, Kleijmeer MJ, Keler T, Zeelenberg I, van Dijk MA, Leusen JH et al. The FcγRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain. Blood 1999; 94: 808–817.

    Article  CAS  PubMed  Google Scholar 

  38. Li X, Su K, Ji C, Szalai AJ, Wu J, Zhang Y et al. Immune opsonins modulate BlyS/BAFF release in a receptor-specific fashion. J Immunol 2008; 181: 1012–1018.

    Article  CAS  PubMed  Google Scholar 

  39. Bolland S, Ravetch JV . Inhibitory pathways triggered by ITIM-containing receptors. Adv Immunol 1999; 72: 149–177.

    Article  CAS  PubMed  Google Scholar 

  40. Bolland S, Ravetch JV . Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 2000; 13: 277–285.

    Article  CAS  PubMed  Google Scholar 

  41. McGaha TL, Sorrentino B, Ravetch JV . Restoration of tolerance in lupus by targeted inhibitory receptor expression. Science 2005; 307: 590–593.

    Article  CAS  PubMed  Google Scholar 

  42. Barrow AD, Trowsdale J . You say ITAM and I say ITIM, let's call the whole thing off: the ambiguity of immunoreceptor signaling. Eur J Immunol 2006; 36: 1646–1653.

    Article  CAS  PubMed  Google Scholar 

  43. Ivanshikiv LB . Cross-regulation of signaling by ITAM-associated receptors. Nat Immunol 2009; 10: 340–347.

    Article  CAS  Google Scholar 

  44. Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 2008; 358: 900–909.

    Article  CAS  PubMed  Google Scholar 

  45. The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40: 204–210.

    Article  CAS  Google Scholar 

  46. Parren PW, Warmerdam PA, Boeije LC, Arts J, Westerdaal NA, Vlug A et al. On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2. J Clin Invest 1992; 90: 1537–1546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bredius RG, de Vries CE, Troelstra A, van Alphen L, Weening RS, van de Winkel JG et al. Phagocytosis of Staphylococcus aureus and Haemophilus influenzae type B opsonized with polyclonal human IgG1 and IgG2 antibodies. Functional hFc gamma RIIa polymorphism to IgG2. J Immunol 1993; 151: 1463–1472.

    CAS  PubMed  Google Scholar 

  48. Duits AJ, Bootsma H, Derksen RH, Spronk PE, Kater L, Kallenberg CG et al. Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients. Arthritis Rheum 1995; 38: 1832–1836.

    Article  CAS  PubMed  Google Scholar 

  49. Salmon JE, Millard S, Schachter LA, Arnett FC, Ginzler EM, Gourley MF et al. Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. J Clin Invest 1996; 97: 1348–1354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Song YW, Han CW, Kang SW, Baek HJ, Lee EB, Shin CH et al. Abnormal distribution of Fc gamma receptor type IIa polymorphisms in Korean patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41: 421–426.

    Article  CAS  PubMed  Google Scholar 

  51. Botto M, Theodoridis E, Thompson EM, Beynon HL, Briggs D, Isenberg DA et al. Fc gamma RIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease. Clin Exp Immunol 1996; 104: 264–268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Smyth LJ, Snowden N, Carthy D, Papasteriades C, Hajeer A, Ollier WE . Fc gamma RIIa polymorphism in systemic lupus erythematosus. Ann Rheum Dis 1997; 56: 744–746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Manger K, Repp R, Spriewald BM, Rascu A, Geiger A, Wassmuth R et al. Fcgamma receptor IIa polymorphism in Caucasian patients with systemic lupus erythematosus: association with clinical symptoms. Arthritis Rheum 1998; 41: 1181–1189.

    Article  CAS  PubMed  Google Scholar 

  54. Yap SN, Phipps ME, Manivasagar M, Tan SY, Bosco JJ . Human Fc gamma receptor IIA (FcgammaRIIA) genotyping and association with systemic lupus erythematosus (SLE) in Chinese and Malays in Malaysia. Lupus 1999; 8: 305–310.

    Article  CAS  PubMed  Google Scholar 

  55. Chen JY, Wang CM, Tsao KC, Chow YH, Wu JM, Li CL et al. Fcgamma receptor IIa, IIIa, and IIIb polymorphisms of systemic lupus erythematosus in Taiwan. Ann Rheum Dis 2004; 63: 877–880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Karassa FB, Trikalinos TA, Ioannidis JP . Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Arthritis Rheum 2002; 46: 1563–1571.

    Article  CAS  PubMed  Google Scholar 

  57. Haseley LA, Wisnieski JJ, Denburg MR, Michael-Grossman AR, Ginzler EM, Gourley MF et al. Antibodies to C1q in systemic lupus erythematosus: characteristics and relation to Fc gamma RIIA alleles. Kidney Int 1997; 52: 1375–1380.

    Article  CAS  PubMed  Google Scholar 

  58. Li X, Wu J, Carter RH, Edberg JC, Su K, Cooper GS et al. A novel polymorphism in the Fcgamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Arthritis Rheum 2003; 48: 3242–3252.

    Article  CAS  PubMed  Google Scholar 

  59. Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato H, Yamaguchi A et al. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis Rheum 2002; 46: 1242–1254.

    Article  CAS  PubMed  Google Scholar 

  60. Kono H, Kyogoku C, Suzuki T, Tsuchiya N, Honda H, Yamamoto K et al. FcgammaRIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling. Hum Mol Genet 2005; 14: 2881–2892.

    Article  CAS  PubMed  Google Scholar 

  61. Floto RA, Clatworthy MR, Heilbronn KR, Rosner DR, MacAry PA, Rankin A et al. Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts. Nat Med 2005; 11: 1056–1058.

    Article  CAS  PubMed  Google Scholar 

  62. Chu ZT, Tsuchiya N, Kyogoku C, Ohashi J, Qian YP, Xu SB et al. Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Tissue Antigens 2004; 63: 21–27.

    Article  CAS  PubMed  Google Scholar 

  63. Siriboonrit U, Tsuchiya N, Sirikong M, Kyogoku C, Bejrachandra S, Suthipinittharm P et al. Association of Fcgamma receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 2003; 61: 374–383.

    Article  CAS  PubMed  Google Scholar 

  64. Magnusson V, Zunec R, Odeberg J, Sturfelt G, Truedsson L, Gunnarsson I et al. Polymorphisms of the Fc gamma receptor type IIB gene are not associated with systemic lupus erythematosus in the Swedish population. Arthritis Rheum 2004; 50: 1348–1350.

    Article  CAS  PubMed  Google Scholar 

  65. Su K, Wu J, Edberg JC, Li X, Ferguson P, Cooper GS et al. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J Immunol 2004; 172: 7186–7191.

    Article  CAS  PubMed  Google Scholar 

  66. Su K, Li X, Edberg JC, Wu J, Ferguson P, Kimberly RP . A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function. J Immunol 2004; 172: 7192–7199.

    Article  CAS  PubMed  Google Scholar 

  67. Blank MC, Stefanescu RN, Masuda E, Marti F, King PD, Redecha PB et al. Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus. Hum Genet 2005; 117: 220–227.

    Article  CAS  PubMed  Google Scholar 

  68. Vance BA, Huizinga TW, Wardwell K, Guyre PM . Binding of monomeric human IgG defines an expression polymorphism of Fc gamma RIII on large granular lymphocyte/natural killer cells. J Immunol 1993; 151: 6429–6439.

    CAS  PubMed  Google Scholar 

  69. Wu J, Edberg JC, Redecha PB, Bansal V, Guyre PM, Coleman K et al. A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest 1997; 100: 1059–1070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Koene HR, Kleijer M, Algra J, Roos D, von dem Borne AE, de Haas M . Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48 L/R/H phenotype. Blood 1997; 90: 1109–1114.

    Article  CAS  PubMed  Google Scholar 

  71. Alarcon GS, McGwin Jr G, Petri M, Ramsey-Goldman R, Fessler BJ, Vila LM et al. Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort. PLoS Med 2006; 3: e396.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ravetch JV, Perussia B . Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med 1989; 170: 481–497.

    Article  CAS  PubMed  Google Scholar 

  73. Hatta Y, Tsuchiya N, Ohashi J, Matsushita M, Fujiwara K, Hagiwara K et al. Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorphisms with systemic lupus erythematosus in Japanese. Genes Immun 1999; 1: 53–60.

    Article  CAS  PubMed  Google Scholar 

  74. Ptacek T, Li X, Edberg JC . Copy number variants in genetic susceptibility and severity of systemic lupus erythematosus. Cytogenet Genome Res 2008; 123: 142–147.

    Article  CAS  PubMed  Google Scholar 

  75. Clark MR, Liu L, Carkson SB, Ory PA, Golstein IM . An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus. J clin Invest 1990; 86: 341–346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Huizinga TWJ, Kuijpers RWAM, Kleijer M, Schulpen TWJ, Cuypers TM, Roos D et al. Maternal genomic neutrophil FcRIII deficiency leading to neonatal isoimmune neutropenia. Blood 1990; 76: 1927–1932.

    Article  CAS  PubMed  Google Scholar 

  77. Koene HR, Kleijer M, Roos D, de Haas M, Von dem Borne AEGKr . FcγRIIIB gene duplication: evidence for presence and expression of three distinct FcγRIIIB genes in NA(1+,2+)Sh(+) individuals. Blood 1998; 91: 673–679.

    Article  CAS  PubMed  Google Scholar 

  78. Aitman TJ, Dong R, Vyse TJ, Norsworthy PJ, Johnson MD, Smith J et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 2006; 439: 851–855.

    Article  CAS  PubMed  Google Scholar 

  79. Fanciulli M, Norsworthy PJ, Petretto E, Dong R, Harper L, Kamesh L et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific autoimmunity. Nat Genet 2007; 39: 721–723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Willcocks LC, Lyons PA, Clatworthy MR, Robinson JI, Yang W, Newland SA et al. Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. J Exp Med 2008; 205: 1573–1582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. de Haas M, Kleijer M, van Zwieten R, Roos D, von dem Borne AEGKr . Neutrophil FcγRIIIb deficiency, nature and clinical consequences: a study of 21 individuals from 14 families. Blood 1995; 86: 2403–2412.

    Article  CAS  PubMed  Google Scholar 

  82. Salmon JE, Ng S, Yoo DH, Kim TH, Kim SY, Song GG . Altered distribution of Fcgamma receptor IIIA alleles in a cohort of Korean patients with lupus nephritis. Arthritis Rheum 1999; 42: 818–819.

    Article  CAS  PubMed  Google Scholar 

  83. Vazquez-Doval J, Sanchez-Ibarrola A . Defective mononuclear phagocyte function in systemic lupus erythematosus: relationship of FcRII (CD32) with intermediate cytoskeletal filaments. J Investig Allergol Clin Immunol 1993; 3: 86–91.

    CAS  PubMed  Google Scholar 

  84. Seligman VA, Suarez C, Lum R, Inda SE, Lin D, Li H et al. The Fcgamma receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians. Arthritis Rheum 2001; 44: 618–625.

    Article  CAS  PubMed  Google Scholar 

  85. Clarkson SB, Kimberly RP, Valinsky JE, Witmer MD, Bussel JB, Nachman RL et al. Blockade of clearance of immune complexes by an anti-Fc gamma receptor monoclonal antibody. J Exp Med 1986; 164: 474–489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hong CH, Lee JS, Lee HS, Bae SC, Yoo DH . The association between fcgammaRIIIB polymorphisms and systemic lupus erythematosus in Korea. Lupus 2005; 14: 346–350.

    Article  CAS  PubMed  Google Scholar 

  87. Kyogoku C, Tsuchiya N, Wu H, Tsao BP, Tokunaga K . Association of Fcgamma receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: a family-based association study in Caucasians. Arthritis Rheum 2004; 50: 671–673.

    Article  CAS  PubMed  Google Scholar 

  88. Gittinger FS, Schindler-Wuepper L, Kissel K, Bux J . Quantitative determination of Fcgamma receptor genes by means of fluorescence-based real-time polymerase chain reaction. Tissue Antigens 2002; 60: 64–70.

    Article  CAS  PubMed  Google Scholar 

  89. Price TH, Bowden RA, Boeckh M, Bux J, Nelson K, Liles WC et al. Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation. Blood 2000; 95: 3302–3309.

    Article  CAS  PubMed  Google Scholar 

  90. Inoue K, Lupski JR . Molecular mechanisms for genomic disorders. Annu Rev Genomics Hum Genet 2002; 3: 199–242.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr Robert P Kimberly for his continued support. Travis Ptacek was supported by the UAB Hughes Med-Grad Fellowship Program. Our work is supported by grants RO1-AR42476, RO1-AR33062 and P01-AR49084 from NIH-NIAMS and by 1UL1RR025777 from the NIH National Center for Research Resources.

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Authors and Affiliations

  1. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    X Li, T S Ptacek, E E Brown & J C Edberg

  2. Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL, USA

    X Li

  3. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    T S Ptacek

  4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    E E Brown

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Correspondence to J C Edberg.

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Li, X., Ptacek, T., Brown, E. et al. Fcγ receptors: structure, function and role as genetic risk factors in SLE. Genes Immun 10, 380–389 (2009). https://doi.org/10.1038/gene.2009.35

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