Abstract
The characteristic finding of high levels of circulating immune complexes in patients with the autoimmune connective tissue diseases systemic lupus erythematosus (SLE) or scleroderma has raised the possibility that these patients may have a primary defect in immune complex clearance. The Fc receptor for IgG (Fc gamma R) plays a central role in the phagocytosis of antibody complexes. We have analysed Fc gamma R (type II) RFLPs identified in TaqI- and MspI-restricted genomic DNA and found that their distribution in SLE and scleroderma did not differ significantly from controls. Hybridization with specific regions of the Fc gamma RII cDNA clone indicate that part of the Fc gamma RII alpha locus is duplicated in some individuals. A further Fc gamma RII gene has recently been identified (Fc gamma RII alpha'). This gene shows greater than 95% homology with Fc gamma RII alpha and may thus be the candidate gene for the apparent alpha duplication seen in some individuals. It is possible that an individual may possess one, two, three or four TaqI Fc gamma RII alpha/alpha' alleles, correlating with incidence and numerical heterogeneity in Fc gamma RII alpha and alpha'. The physiological effects of this numerical heterogeneity remain to be investigated.
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- Anderson C. L., Ryan D. H., Looney R. J., Leary P. C. Structural polymorphism of the human monocyte 40 kilodalton Fc receptor for IgG. J Immunol. 1987 Apr 1;138(7):2254–2256. [PubMed] [Google Scholar]
- Arnett F. C., Reveille J. D., Wilson R. W., Provost T. T., Bias W. B. Systemic lupus erythematosus: current state of the genetic hypothesis. Semin Arthritis Rheum. 1984 Aug;14(1):24–35. doi: 10.1016/0049-0172(84)90006-4. [DOI] [PubMed] [Google Scholar]
- Boot J. H., Geerts M. E., Aarden L. A. Functional polymorphisms of Fc receptors in human monocyte-mediated cytotoxicity towards erythrocytes induced by murine isotype switch variants. J Immunol. 1989 Feb 15;142(4):1217–1223. [PubMed] [Google Scholar]
- Brooks D. G., Qiu W. Q., Luster A. D., Ravetch J. V. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med. 1989 Oct 1;170(4):1369–1385. doi: 10.1084/jem.170.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Z. Y., Virella G., Tung H. E., Ainsworth S. K., Silver R. M., Wang A. C., LaVia M. F., Maricq H. R., Dobson R. L. Immune complexes and antinuclear, antinucleolar, and anticentromere antibodies in scleroderma. J Am Acad Dermatol. 1984 Sep;11(3):461–467. doi: 10.1016/s0190-9622(84)70191-5. [DOI] [PubMed] [Google Scholar]
- Debets J. M., Van der Linden C. J., Dieteren I. E., Leeuwenberg J. F., Buurman W. A. Fc-receptor cross-linking induces rapid secretion of tumor necrosis factor (cachectin) by human peripheral blood monocytes. J Immunol. 1988 Aug 15;141(4):1197–1201. [PubMed] [Google Scholar]
- Dunckley H., Gatenby P. A., Serjeantson S. W. DNA typing of HLA-DR antigens in systemic lupus erythematosus. Immunogenetics. 1986;24(3):158–162. doi: 10.1007/BF00364743. [DOI] [PubMed] [Google Scholar]
- Elbein S. C., Corsetti L., Ullrich A., Permutt M. A. Multiple restriction fragment length polymorphisms at the insulin receptor locus: a highly informative marker for linkage analysis. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5223–5227. doi: 10.1073/pnas.83.14.5223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frank M. M., Hamburger M. I., Lawley T. J., Kimberly R. P., Plotz P. H. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med. 1979 Mar 8;300(10):518–523. doi: 10.1056/NEJM197903083001002. [DOI] [PubMed] [Google Scholar]
- Grundy H. O., Peltz G., Moore K. W., Golbus M. S., Jackson L. G., Lebo R. V. The polymorphic Fc gamma receptor II gene maps to human chromosome 1q. Immunogenetics. 1989;29(5):331–339. doi: 10.1007/BF00352843. [DOI] [PubMed] [Google Scholar]
- Hibbs M. L., Bonadonna L., Scott B. M., McKenzie I. F., Hogarth P. M. Molecular cloning of a human immunoglobulin G Fc receptor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2240–2244. doi: 10.1073/pnas.85.7.2240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jazwinska E. C., Dunckley H., Gatenby P. A., Serjeantson S. W. Gm allogenotype distribution and lack of HLA-DR, Gm interaction in SLE and CREST/PSS. Immunol Cell Biol. 1989 Aug;67(Pt 4):261–265. doi: 10.1038/icb.1989.39. [DOI] [PubMed] [Google Scholar]
- Mellman I. S., Plutner H., Steinman R. M., Unkeless J. C., Cohn Z. A. Internalization and degradation of macrophage Fc receptors during receptor-mediated phagocytosis. J Cell Biol. 1983 Mar;96(3):887–895. doi: 10.1083/jcb.96.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Neill G. J., Miniter P., Pollack M. S., Dupont B. Different HLA antigen associations for the functionally active and inactive products of the complement C4F1 allele. Hum Immunol. 1980 Jul;1(1):23–30. doi: 10.1016/0198-8859(80)90006-3. [DOI] [PubMed] [Google Scholar]
- Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980 May;23(5):581–590. doi: 10.1002/art.1780230510. [DOI] [PubMed] [Google Scholar]
- Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salmon J. E., Kimberly R. P., Gibofsky A., Fotino M. Altered phagocytosis by monocytes from HLA-DR2 and DR3-positive healthy adults is Fc gamma receptor specific. J Immunol. 1986 May 15;136(10):3625–3630. [PubMed] [Google Scholar]
- Seki T. Identification of multiple isoforms of the low-affinity human IgG Fc receptor. Immunogenetics. 1989;30(1):5–12. doi: 10.1007/BF02421463. [DOI] [PubMed] [Google Scholar]
- Senaldi G., Lupoli S., Vergani D., Black C. M. Activation of the complement system in systemic sclerosis. Relationship to clinical severity. Arthritis Rheum. 1989 Oct;32(10):1262–1267. doi: 10.1002/anr.1780321011. [DOI] [PubMed] [Google Scholar]
- Steen V. D., Ziegler G. L., Rodnan G. P., Medsger T. A., Jr Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum. 1984 Feb;27(2):125–131. doi: 10.1002/art.1780270202. [DOI] [PubMed] [Google Scholar]
- Stuart S. G., Simister N. E., Clarkson S. B., Kacinski B. M., Shapiro M., Mellman I. Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium. EMBO J. 1989 Dec 1;8(12):3657–3666. doi: 10.1002/j.1460-2075.1989.tb08540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuart S. G., Trounstine M. L., Vaux D. J., Koch T., Martens C. L., Mellman I., Moore K. W. Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII). J Exp Med. 1987 Dec 1;166(6):1668–1684. doi: 10.1084/jem.166.6.1668. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
- Unkeless J. C. Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest. 1989 Feb;83(2):355–361. doi: 10.1172/JCI113891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willis H. E., Browder B., Feister A. J., Mohanakumar T., Ruddy S. Monoclonal antibody to human IgG Fc receptors. Cross-linking of receptors induces lysosomal enzyme release and superoxide generation by neutrophils. J Immunol. 1988 Jan 1;140(1):234–239. [PubMed] [Google Scholar]