Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jul;86(1):341–346. doi: 10.1172/JCI114706

An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus.

M R Clark 1, L Liu 1, S B Clarkson 1, P A Ory 1, I M Goldstein 1
PMCID: PMC296727  PMID: 1694867

Abstract

In the course of examining the structure and function of Fc receptors on peripheral blood cells of patients with systemic lupus erythematosus, we identified a patient whose neutrophils did not react with either monoclonal or polyclonal antibodies to Fc receptor III. However, neutrophils from the patient were comparable to neutrophils from healthy controls with respect to their expression of Fc receptor II, complement receptor 1, complement receptor 3, and the phosphatidylinositol-linked, complement regulatory protein, decay-accelerating factor. The abnormality of expression of Fc receptor III was limited to the patient's neutrophils (her natural killer cells reacted normally with anti-Fc receptor III antibodies), and was associated with abnormal recognition and binding of IgG-coated erythrocytes. Analysis of genomic DNA revealed evidence that failure of the patient's neutrophils to express Fc receptor III was most likely due to an abnormality of the gene that encodes this receptor.

Full text

PDF
341

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bollag R. J., Waldman A. S., Liskay R. M. Homologous recombination in mammalian cells. Annu Rev Genet. 1989;23:199–225. doi: 10.1146/annurev.ge.23.120189.001215. [DOI] [PubMed] [Google Scholar]
  3. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  4. Ceuppens J. L., Baroja M. L., Van Vaeck F., Anderson C. L. Defect in the membrane expression of high affinity 72-kD Fc gamma receptors on phagocytic cells in four healthy subjects. J Clin Invest. 1988 Aug;82(2):571–578. doi: 10.1172/JCI113634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Changelian P. S., Jack R. M., Collins L. A., Fearon D. T. PMA induces the ligand-independent internalization of CR1 on human neutrophils. J Immunol. 1985 Mar;134(3):1851–1858. [PubMed] [Google Scholar]
  6. Clarkson S. B., Bussel J. B., Kimberly R. P., Valinsky J. E., Nachman R. L., Unkeless J. C. Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody. N Engl J Med. 1986 May 8;314(19):1236–1239. doi: 10.1056/NEJM198605083141907. [DOI] [PubMed] [Google Scholar]
  7. Clarkson S. B., Kimberly R. P., Valinsky J. E., Witmer M. D., Bussel J. B., Nachman R. L., Unkeless J. C. Blockade of clearance of immune complexes by an anti-Fc gamma receptor monoclonal antibody. J Exp Med. 1986 Aug 1;164(2):474–489. doi: 10.1084/jem.164.2.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edberg J. C., Redecha P. B., Salmon J. E., Kimberly R. P. Human Fc gamma RIII (CD16). Isoforms with distinct allelic expression, extracellular domains, and membrane linkages on polymorphonuclear and natural killer cells. J Immunol. 1989 Sep 1;143(5):1642–1649. [PubMed] [Google Scholar]
  9. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Hamburger M. I., Lawley T. J., Kimberly R. P., Plotz P. H., Frank M. M. A serial study of splenic reticuloendothelial system Fc receptor functional activity in systemic lupus erythematosus. Arthritis Rheum. 1982 Jan;25(1):48–54. doi: 10.1002/art.1780250108. [DOI] [PubMed] [Google Scholar]
  12. Haziot A., Chen S., Ferrero E., Low M. G., Silber R., Goyert S. M. The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol. 1988 Jul 15;141(2):547–552. [PubMed] [Google Scholar]
  13. Higgs D. R., Vickers M. A., Wilkie A. O., Pretorius I. M., Jarman A. P., Weatherall D. J. A review of the molecular genetics of the human alpha-globin gene cluster. Blood. 1989 Apr;73(5):1081–1104. [PubMed] [Google Scholar]
  14. Huizinga T. W., van Kemenade F., Koenderman L., Dolman K. M., von dem Borne A. E., Tetteroo P. A., Roos D. The 40-kDa Fc gamma receptor (FcRII) on human neutrophils is essential for the IgG-induced respiratory burst and IgG-induced phagocytosis. J Immunol. 1989 Apr 1;142(7):2365–2369. [PubMed] [Google Scholar]
  15. Huizinga T. W., van der Schoot C. E., Jost C., Klaassen R., Kleijer M., von dem Borne A. E., Roos D., Tetteroo P. A. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Nature. 1988 Jun 16;333(6174):667–669. doi: 10.1038/333667a0. [DOI] [PubMed] [Google Scholar]
  16. Jack R. M., Fearon D. T. Selective synthesis of mRNA and proteins by human peripheral blood neutrophils. J Immunol. 1988 Jun 15;140(12):4286–4293. [PubMed] [Google Scholar]
  17. Kinoshita T., Medof M. E., Silber R., Nussenzweig V. Distribution of decay-accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Med. 1985 Jul 1;162(1):75–92. doi: 10.1084/jem.162.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lanier L. L., Ruitenberg J. J., Phillips J. H. Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J Immunol. 1988 Nov 15;141(10):3478–3485. [PubMed] [Google Scholar]
  19. Looney R. J., Ryan D. H., Takahashi K., Fleit H. B., Cohen H. J., Abraham G. N., Anderson C. L. Identification of a second class of IgG Fc receptors on human neutrophils. A 40 kilodalton molecule also found on eosinophils. J Exp Med. 1986 Apr 1;163(4):826–836. doi: 10.1084/jem.163.4.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Low M. G. Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J. 1987 May 15;244(1):1–13. doi: 10.1042/bj2440001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ory P. A., Clark M. R., Kwoh E. E., Clarkson S. B., Goldstein I. M. Sequences of complementary DNAs that encode the NA1 and NA2 forms of Fc receptor III on human neutrophils. J Clin Invest. 1989 Nov;84(5):1688–1691. doi: 10.1172/JCI114350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ory P. A., Goldstein I. M., Kwoh E. E., Clarkson S. B. Characterization of polymorphic forms of Fc receptor III on human neutrophils. J Clin Invest. 1989 May;83(5):1676–1681. doi: 10.1172/JCI114067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parris T. M., Kimberly R. P., Inman R. D., McDougal J. S., Gibofsky A., Christian C. L. Defective Fc receptor-mediated function of the mononuclear phagocyte system in lupus nephritis. Ann Intern Med. 1982 Oct;97(4):526–532. doi: 10.7326/0003-4819-97-4-526. [DOI] [PubMed] [Google Scholar]
  24. Peltz G. A., Grundy H. O., Lebo R. V., Yssel H., Barsh G. S., Moore K. W. Human Fc gamma RIII: cloning, expression, and identification of the chromosomal locus of two Fc receptors for IgG. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1013–1017. doi: 10.1073/pnas.86.3.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perussia B., Trinchieri G., Jackson A., Warner N. L., Faust J., Rumpold H., Kraft D., Lanier L. L. The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. J Immunol. 1984 Jul;133(1):180–189. [PubMed] [Google Scholar]
  26. Ravetch J. V., 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 Aug 1;170(2):481–497. doi: 10.1084/jem.170.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  28. Scallon B. J., Scigliano E., Freedman V. H., Miedel M. C., Pan Y. C., Unkeless J. C., Kochan J. P. A human immunoglobulin G receptor exists in both polypeptide-anchored and phosphatidylinositol-glycan-anchored forms. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5079–5083. doi: 10.1073/pnas.86.13.5079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Selvaraj P., Rosse W. F., Silber R., Springer T. A. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature. 1988 Jun 9;333(6173):565–567. doi: 10.1038/333565a0. [DOI] [PubMed] [Google Scholar]
  30. Simmons D., Seed B. The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568–570. doi: 10.1038/333568a0. [DOI] [PubMed] [Google Scholar]
  31. Tosi M. F., Berger M. Functional differences between the 40 kDa and 50 to 70 kDa IgG Fc receptors on human neutrophils revealed by elastase treatment and antireceptor antibodies. J Immunol. 1988 Sep 15;141(6):2097–2103. [PubMed] [Google Scholar]
  32. Ueda E., Kinoshita T., Nojima J., Inoue K., Kitani T. Different membrane anchors of Fc gamma RIII (CD16) on K/NK-lymphocytes and neutrophils. Protein- vs lipid-anchor. J Immunol. 1989 Aug 15;143(4):1274–1277. [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES