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. 1993 Sep;92(3):1181–1187. doi: 10.1172/JCI116688

Defect of a complement receptor 3 epitope in a patient with systemic lupus erythematosus.

T Witte 1, F L Dumoulin 1, J E Gessner 1, J Schubert 1, O Götze 1, C Neumann 1, R F Todd 3rd 1, H Deicher 1, R E Schmidt 1
PMCID: PMC288256  PMID: 7690773

Abstract

Complement receptor 3 (CR3) is expressed on cells of the reticuloendothelial system and involved in the clearance of immune complexes. In this article a patient with a deficiency of the C3bi binding site of this receptor is described. Clinically this patient exhibited predominantly cutaneous manifestations of a systemic lupus erythematosus with an immune vasculitis and panniculitis. The deficiency of the CR3 epitope was demonstrated using flow cytometry. The functional relevance of this defect was demonstrated in a rosetting assay with C3bi-loaded erythrocytes. C3bi binding was found to be significantly decreased. Furthermore, there was an impairment of phagocytosis of opsonized Escherichia coli. The CR3 defect is not due to an autoantibody but is assumed to have a genetic basis. These data suggest that the defect of the CR3 may be involved in the pathogenesis of the immune vasculitis in this patient.

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Selected References

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

  1. Alsenz J., Bork K., Loos M. Autoantibody-mediated acquired deficiency of C1 inhibitor. N Engl J Med. 1987 May 28;316(22):1360–1366. doi: 10.1056/NEJM198705283162202. [DOI] [PubMed] [Google Scholar]
  2. Arnaout M. A., Pitt J., Cohen H. J., Melamed J., Rosen F. S., Colten H. R. Deficiency of a granulocyte-membrane glycoprotein (gp150) in a boy with recurrent bacterial infections. N Engl J Med. 1982 Mar 25;306(12):693–699. doi: 10.1056/NEJM198203253061201. [DOI] [PubMed] [Google Scholar]
  3. Atkinson J. P. Complement deficiency. Predisposing factor to autoimmune syndromes. Am J Med. 1988 Dec 23;85(6A):45–47. doi: 10.1016/0002-9343(88)90383-x. [DOI] [PubMed] [Google Scholar]
  4. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  5. Boros P., Chen J. M., Bona C., Unkeless J. C. Autoimmune mice make anti-Fc gamma receptor antibodies. J Exp Med. 1990 May 1;171(5):1581–1595. doi: 10.1084/jem.171.5.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown E. J., Bohnsack J. F., Gresham H. D. Mechanism of inhibition of immunoglobulin G-mediated phagocytosis by monoclonal antibodies that recognize the Mac-1 antigen. J Clin Invest. 1988 Feb;81(2):365–375. doi: 10.1172/JCI113328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Clark M. R., Liu L., Clarkson S. B., Ory P. A., Goldstein I. M. An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus. J Clin Invest. 1990 Jul;86(1):341–346. doi: 10.1172/JCI114706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cole F. S., Whitehead A. S., Auerbach H. S., Lint T., Zeitz H. J., Kilbridge P., Colten H. R. The molecular basis for genetic deficiency of the second component of human complement. N Engl J Med. 1985 Jul 4;313(1):11–16. doi: 10.1056/NEJM198507043130103. [DOI] [PubMed] [Google Scholar]
  10. Dana N., Fathallah D. M., Arnaout M. A. Expression of a soluble and functional form of the human beta 2 integrin CD11b/CD18. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3106–3110. doi: 10.1073/pnas.88.8.3106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dana N., Styrt B., Griffin J. D., Todd R. F., 3rd, Klempner M. S., Arnaout M. A. Two functional domains in the phagocyte membrane glycoprotein Mo1 identified with monoclonal antibodies. J Immunol. 1986 Nov 15;137(10):3259–3263. [PubMed] [Google Scholar]
  12. Dana N., Todd R. F., 3rd, Pitt J., Springer T. A., Arnaout M. A. Deficiency of a surface membrane glycoprotein (Mo1) in man. J Clin Invest. 1984 Jan;73(1):153–159. doi: 10.1172/JCI111186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fearon D. T. Complement, C receptors, and immune complex disease. Hosp Pract (Off Ed) 1988 Aug 15;23(8):63–72. doi: 10.1080/21548331.1988.11703520. [DOI] [PubMed] [Google Scholar]
  14. Freyer D. R., Morganroth M. L., Rogers C. E., Arnaout M. A., Todd R. F., 3rd Modulation of surface CD11/CD18 glycoproteins (Mo1, LFA-1, p150,95) by human mononuclear phagocytes. Clin Immunol Immunopathol. 1988 Feb;46(2):272–283. doi: 10.1016/0090-1229(88)90189-4. [DOI] [PubMed] [Google Scholar]
  15. Goldstein R., Arnett F. C., McLean R. H., Bias W. B., Duvic M. Molecular heterogeneity of complement component C4-null and 21-hydroxylase genes in systemic lupus erythematosus. Arthritis Rheum. 1988 Jun;31(6):736–744. doi: 10.1002/art.1780310606. [DOI] [PubMed] [Google Scholar]
  16. Hendrich C., Kuipers J. G., Kolanus W., Hammer M., Schmidt R. E. Activation of CD16+ effector cells by rheumatoid factor complex. Role of natural killer cells in rheumatoid arthritis. Arthritis Rheum. 1991 Apr;34(4):423–431. doi: 10.1002/art.1780340407. [DOI] [PubMed] [Google Scholar]
  17. Hundt M., Schmidt R. E. The glycosylphosphatidylinositol-linked Fc gamma receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Eur J Immunol. 1992 Mar;22(3):811–816. doi: 10.1002/eji.1830220327. [DOI] [PubMed] [Google Scholar]
  18. Kazatchkine M. D., Fearon D. T., Austen K. F. Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B and beta1 H for cell-bound C3b. J Immunol. 1979 Jan;122(1):75–81. [PubMed] [Google Scholar]
  19. MacGregor R. R., Spagnuolo P. J., Lentnek A. L. Inhibition of granulocyte adherence by ethanol, prednisone, and aspirin, measured with an assay system. N Engl J Med. 1974 Sep 26;291(13):642–646. doi: 10.1056/NEJM197409262911302. [DOI] [PubMed] [Google Scholar]
  20. Myones B. L., Dalzell J. G., Hogg N., Ross G. D. Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3. J Clin Invest. 1988 Aug;82(2):640–651. doi: 10.1172/JCI113643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Müller-Eberhard H. J. Molecular organization and function of the complement system. Annu Rev Biochem. 1988;57:321–347. doi: 10.1146/annurev.bi.57.070188.001541. [DOI] [PubMed] [Google Scholar]
  22. Nadler L. M., Stashenko P., Hardy R., van Agthoven A., Terhorst C., Schlossman S. F. Characterization of a human B cell-specific antigen (B2) distinct from B1. J Immunol. 1981 May;126(5):1941–1947. [PubMed] [Google Scholar]
  23. Pryzwansky K. B., Wyatt T., Reed W., Ross G. D. Phorbol ester induces transient focal concentrations of functional, newly expressed CR3 in neutrophils at sites of specific granule exocytosis. Eur J Cell Biol. 1991 Feb;54(1):61–75. [PubMed] [Google Scholar]
  24. Ross G. D., Cain J. A., Lachmann P. J. Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol. 1985 May;134(5):3307–3315. [PubMed] [Google Scholar]
  25. Rynes R. I. Inherited complement deficiency states and SLE. Clin Rheum Dis. 1982 Apr;8(1):29–47. [PubMed] [Google Scholar]
  26. Schifferli J. A., Ng Y. C., Estreicher J., Walport M. J. The clearance of tetanus toxoid/anti-tetanus toxoid immune complexes from the circulation of humans. Complement- and erythrocyte complement receptor 1-dependent mechanisms. J Immunol. 1988 Feb 1;140(3):899–904. [PubMed] [Google Scholar]
  27. Schifferli J. A., Ng Y. C., Paccaud J. P., Walport M. J. The role of hypocomplementaemia and low erythrocyte complement receptor type 1 numbers in determining abnormal immune complex clearance in humans. Clin Exp Immunol. 1989 Mar;75(3):329–335. [PMC free article] [PubMed] [Google Scholar]
  28. Schifferli J. A., Ng Y. C., Peters D. K. The role of complement and its receptor in the elimination of immune complexes. N Engl J Med. 1986 Aug 21;315(8):488–495. doi: 10.1056/NEJM198608213150805. [DOI] [PubMed] [Google Scholar]
  29. Schmidt R. E., MacDermott R. P., Bartley G., Bertovich M., Amato D. A., Austen K. F., Schlossman S. F., Stevens R. L., Ritz J. Specific release of proteoglycans from human natural killer cells during target lysis. Nature. 1985 Nov 21;318(6043):289–291. doi: 10.1038/318289a0. [DOI] [PubMed] [Google Scholar]
  30. Schmidt R. E., Michon J. M., Woronicz J., Schlossman S. F., Reinherz E. L., Ritz J. Enhancement of natural killer function through activation of the T11 E rosette receptor. J Clin Invest. 1987 Jan;79(1):305–308. doi: 10.1172/JCI112800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smiley J. D., Moore S. E., Jr Immune-complex vasculitis: role of complement and IgG-Fc receptor functions. Am J Med Sci. 1989 Oct;298(4):267–277. doi: 10.1097/00000441-198910000-00012. [DOI] [PubMed] [Google Scholar]
  32. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Vedder N. B., Harlan J. M. Increased surface expression of CD11b/CD18 (Mac-1) is not required for stimulated neutrophil adherence to cultured endothelium. J Clin Invest. 1988 Mar;81(3):676–682. doi: 10.1172/JCI113372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Werfel T., Uciechowski P., Tetteroo P. A., Kurrle R., Deicher H., Schmidt R. E. Activation of cloned human natural killer cells via Fc gamma RIII. J Immunol. 1989 Feb 15;142(4):1102–1106. [PubMed] [Google Scholar]
  36. Werfel T., Witter W., Götze O. CD11b and CD11c antigens are rapidly increased on human natural killer cells upon activation. J Immunol. 1991 Oct 1;147(7):2423–2427. [PubMed] [Google Scholar]
  37. Witte T., Wordelmann K., Schmidt R. E. Heterogeneity of human natural killer cells in the spleen. Immunology. 1990 Jan;69(1):166–170. [PMC free article] [PubMed] [Google Scholar]

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