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C3b receptor (CR1) genomic polymorphism in rheumatoid arthritis

Low receptor levels on erythrocytes are an acquired phenomenon

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Abstract

The number of complement receptor 1 (CR1, CD35) molecules on erythrocytes is genetically determined by two codominant alleles. The numerical expression of CR1 on erythrocytes correlates with aHindIII-RFLP of CR1 gene using CR1-1, a complementary DNA probe. We have found low CR1 on erythrocytes in patients with rheumatoid arthritis (RA) in an Indian population. Low levels in RA patients may be acquired or genetically determined. Fifty-two patients with RA, 48 nonrelated healthy subjects and 19 consanguineous relatives of patients were genotyped. CR1 numbers on erythrocytes were quantitated by the enzyme-linked immunosorbent assay using monoclonal anti-CR1 antibody. Normal subjects and patients were followed up for a period of 6 months to evaluate the stability of their CR1 expression. The gene frequency for allele H and L (7.4- and 6.9-kbHindIII restriction fragment, respectively), which correlated with high and low expression of CR1 on erythrocytes was 0.77 and 0.23 in the normal controls. Gene frequency in RA patients was 0.78 and 0.22 for H and L allele, which did not differ significantly from either controls or relatives (0.80 and 0.20 for H and L allele, respectively). However, RA patients expressed fewer CR1 on erythrocytes within each genotype than their relatives and controls. CR1 on erythrocytes were found to be stable in consecutive samples in controls. In RA patients, the number varied between low and high during the course of the disease. The variation in number was significantly correlated (p <0.05, r=−0.85 to −0.98) with disease activity as monitored by erythrocyte sedimentation rate. Our results suggest that low levels of CR1 on erythrocytes in patients with RA are not inherited, rather they are acquired during the course of the disease.

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References

  1. Fearon DT: Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B-lymphocyte and monocyte. J Exp Med 1980;152:20–30.

    Article  PubMed  CAS  Google Scholar 

  2. Fischer E, Capron M, Prin L, Kusnierz JP, Kazatchkine MD: Human eosinophils express CR1 and CR3 complement receptors for cleavage fragment of C3. Cell Immunol 1986; 97:297–306.

    Article  PubMed  CAS  Google Scholar 

  3. Huber H, Polly MJ, Linscott WD, Fudenberg HH, Muller HJ: Human monocyte has distinct receptor site for the complement and for immunoglobulin G. Science 1968;162:1281–1283.

    Article  PubMed  CAS  Google Scholar 

  4. Cohen JHM, Aubry JP, Kazatchkine MD: CR1 bearing human T-cells are exclusively found within the CD4+ subset. Complement 1987;4:143–144.

    Google Scholar 

  5. Wilson JG, Tedder TF, Fearon DT: Characterization of human T-lymphocytes that express the C3b receptor. J Immunol 1983;131:684–689.

    PubMed  CAS  Google Scholar 

  6. Raynes M, Aubert JP, Cohen JHM, Audouin J, Tricoffef V, Diebold J, Kazatchkine MD: Human follicular dendritic cells express CR1, CR2 and CR3 complement receptor antigens. J Immunol 1985;135:2687–2694.

    Google Scholar 

  7. Biber T, Human D, Heid E: The cells of histocytes x express C3b, C3d and C3bi receptor (CR1, CR2, and CR3) antigens. Arch Dermatol Res 1985;277:496–502.

    Article  Google Scholar 

  8. Emancipator SN, Iida K, Nussenzweig V, Gallo GR: Monoclonal antibodies to human complement receptor (CR1) detect defects in glomerular diseases. Clin Immunol Immunopathol 1983;27:170–175.

    Article  PubMed  CAS  Google Scholar 

  9. Yoon SH, Fearon DT: Characterization of a soluble form of the C3b/C4b receptor in human plasma. J Immunol 1985;134:3332–3338.

    PubMed  CAS  Google Scholar 

  10. Carnacoff JB, Herbert LA, Smead WL, Van Aman ME, Birmingham DJ, Waxman FJ: Primate erythrocyte immune complex clearing mechanism. J Clin Invest 1983;71:236–247.

    Article  Google Scholar 

  11. Ehlenberger AG, Nussenzweig V: The role of membrane receptor for C3b and C3d in phagocytosis. J Exp Med 1977;145:357–371.

    Article  PubMed  CAS  Google Scholar 

  12. Fearon DT, Kaneko I, Thomson GG: Membrane distribution and adsorptive endocytosis of C3b receptor of human polymorphonuclear leukocytes. J Exp Med 1981; 145:357–371.

    Google Scholar 

  13. Daha MR, Bloem AC, Ballieux RE: Immunoglobulin production by human peripheral lymphocytes induced by anti-C3 receptor antibodies. J Immunol 1984;132:1197–1201.

    PubMed  CAS  Google Scholar 

  14. Weiss L, Delfraissy JF, Vasquez A, Wallon C, Galanaud P, Kazatchkine MD: Monoclonal antibodies to the human C3b/C4b receptor (CR1) enhance specific B-cell differentiation. J Immunol 1987;138:2988–2993.

    PubMed  CAS  Google Scholar 

  15. Iida K, Mornaghi R, Nussenzweig V: Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus. J Exp Med 1982;155:1427–1438.

    Article  PubMed  CAS  Google Scholar 

  16. Minota S, Terai C, Nojima Y, Takano K, Takai E, Miyakava Y, Takaku F: Low C3b receptor reactivity on erythrocytes from patients with systemic lupus erythematosus detected by immune adherence hemagglutination and radioimmunoassay with monoclonal antibody. Arthritis Rheum 1984;27:1329–1335.

    Article  PubMed  CAS  Google Scholar 

  17. Ross GD, Yount WJ, Walport MJ, Winfield JB, Parker CJ, Fuller CR, Taylor RP, Myones BL, Clachmann PJ: Disease associated loss of erythrocyte complement receptors (CR1, C3b receptor) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. J Immunol 1985;135:2005–2014.

    PubMed  CAS  Google Scholar 

  18. Walport MJ, Ross GD, Young M, Watson JV, Hogg N, Lachmann PJ: Family studies of erythrocyte complement receptor type 1 levels: Reduced levels in patients of SLE are acquired, not inherited. Clin Exp Immunol 1985;59:547–554.

    PubMed  CAS  Google Scholar 

  19. Wilson JG, Wong WW, Shur PH, Fearon DT: Mode of inheritance of decreased C3b receptor on erythrocytes of patients with systemic lupus erythematosus. N Engl J Med 1982;307: 981–986.

    PubMed  CAS  Google Scholar 

  20. Wilson JG, Wong WW, Murphy EE, Schur PH, Fearon DT: Deficiency of the C3b/C4b receptor (CR1) of erythrocytes in systemic lupus erythematosus: Analysis of the stability of defect and of a restriction fragment length polymorphism of the CR1 gene. J Immunol 1987;138: 2706–2710.

    CAS  Google Scholar 

  21. Medof ME, Prince GM, Oger JF: Kinetics of interaction of immune complexes with complement receptor on human blood cells: Modification of complexes during interaction with red cell. Clin Exp Immunol 1982;48:715–725.

    PubMed  CAS  Google Scholar 

  22. Holme E, Fyfe A, Zoma A, Yeitch J Hunter J, Whaley K: Decreased C3b receptors (CR1) on erythrocytes from patients with systemic lupus erythematosus. Clin Exp Immunol 1986;63:41–48.

    PubMed  CAS  Google Scholar 

  23. Satoh H, Yokota E, Tokiyama K, Kawaguchi T, Niho Y: Distribution of the Hind III restriction fragment length polymorphism among patients with systemic lupus erythematosus with different concentrations of CR1. Ann Rheum Dis 1991;50: 765–768.

    Article  PubMed  CAS  Google Scholar 

  24. Cohen JHM, Geffriaud C, Caudwell V, Kezatchkine MD: Genetic analysis of CR1 (the C3b complement receptor, CD35) expression on erythrocytes of HIV-infected individuals. Aids 1989;3:397–399.

    Article  PubMed  CAS  Google Scholar 

  25. Jouvin MH, Rozenbaum W, Russo R: Decreased expression of the C3b/C4b complement receptor (CR1) in AIDS and AIDS related syndromes correlates with clinical subpopulations of patients with HIV infection. Aids 1987;1:89–94.

    PubMed  CAS  Google Scholar 

  26. Tausk FA, McCutchan JA, Spechko P, Schreiber RD, Gigli I: Deficiency of erythrocyte C3b receptor (CR1) in AIDS and AIDS related syndrome. Biosci Res 1986;6:81–86.

    Article  CAS  Google Scholar 

  27. Makela AL, Eerola E, Lehtonen OP, Ruuska P, Lantto R: Erythrocyte C3b receptors in juvenile rheumatoid arthritis. N Engl J Med 1983; 309:673–680.

    PubMed  CAS  Google Scholar 

  28. Ruuska PE, Ikaheimo I, Kassinen SS, Kaar ML, Tiilikainen A: Normal C3b receptor (CR1) genomic polymorphism in patients with insulin dependent diabetes mellitus (IDDM): Is the low erythrocyte CR1 expression an acquired phenomenon? Clin Exp Immunol 1992;89: 18–21.

    PubMed  CAS  Google Scholar 

  29. Wong WW, Wilson JG, Fearon DT: Genetic regulation of a structural polymorphism of C3b receptor. J Clin Invest 1983;72:685–693.

    Article  PubMed  CAS  Google Scholar 

  30. Wilson JG, Murphy EE, Wong, WW, Klickstein LB, Weis JH, Fearon DT: Identification of a restriction fragment length polymorphism by a CR1 cDNA that correlates with the number of CR1 on erythrocytes. J Exp Med 1986;164:50–59.

    Article  PubMed  CAS  Google Scholar 

  31. Inada Y, Kamiyama M, Kanemitsu T, Hyman CL, Clark WS: Studies on immune adherence (C3b) receptor activity of human erythrocytes: Relationship between receptor activity and presence of immune complexes in serum. Clin Exp Immunol 1982; 50:189–197.

    PubMed  CAS  Google Scholar 

  32. Mitchell JA, Batchelor JR, Chapel H, Spiers CN, Sim E: Erythrocyte complement receptor type 1 (CR1) expression and circulating immune complexes (CIC) levels in hydralazine induced SLE. Clin Exp Immunol 1987;68:446–456.

    PubMed  CAS  Google Scholar 

  33. Moldenhauer F, Botto M, Walport MJ: The rate of loss of CR1 from ageing erythrocytes in vivo in normal subjects and SLE patients: No correlation with structural or numerical polymorphisms. Clin Exp Immunol 1988;72:74–78.

    PubMed  CAS  Google Scholar 

  34. Mitchell JA, Sim RB, Sim E: CR1 polymorphism in hydralazine induced systemic lupus erythematosus: DNA restriction fragment length polymorphism. Clin Exp Immunol 1989;78:354–358.

    PubMed  CAS  Google Scholar 

  35. Cohen JHM, Caudwell V, Levi Strauss M, Bourgeois P, Kazatchkine MD: Genetic analysis of CR1 expression on erythrocytes of patients with systemic lupus erythematosus. Arthritis Rheum 1989;32: 393–397.

    Article  PubMed  CAS  Google Scholar 

  36. Tebib MG, Martinez C, Granados J, Segovia DA, Schur PH: The frequency of complement receptor type 1 (CR1) gene polymorphisms in nine families with multiple cases of systemic lupus erythematosus. Arthritis Rheum 1989;32:1465–1469.

    Article  PubMed  CAS  Google Scholar 

  37. Kumar A, Malaviya AN, Srivastava LM: Lowered expression of complement receptor 1 (CR1) in rheumatoid arthritis. Immunobiology 1994; 191:9–20.

    PubMed  CAS  Google Scholar 

  38. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–324.

    Article  PubMed  CAS  Google Scholar 

  39. Arnaut A, Dana N, Melamed J, Medicus R, Colten HR: Low ionic strength or chemical cross linking of monomeric C3b increases its binding affinity to the human C3b receptor. Immunology 1983;48:229–238.

    Google Scholar 

  40. Thomson BS, Nielson H, Bendixen G: Erythrocyte CR1 determination using monoclonal antibody in a microtiter plate ELISA: Receptors are not masked by immune complexes. Allergy 1986;41:477–486.

    Google Scholar 

  41. Kunkel LM, Smith KD, Boyer SH: Analysis of human Y chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 1977;74:1245–1249.

    Article  PubMed  CAS  Google Scholar 

  42. Southern EM: Detection of sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975;98:503–517.

    Article  PubMed  CAS  Google Scholar 

  43. Wong WW, Klickstein LB, Smith JA, Weis JH, Fearon DT: Identification of a partial cDNA clone for the human receptor for complement fragments C3b/C4b. Proc Natl Acad Sci USA 1985;82:7711–7715.

    Article  PubMed  CAS  Google Scholar 

  44. Moldenhauer F, David J, Fielder AHL, Lachmann PJ, Walport MJ: Inherited deficiency of erythrocyte complement receptor type 1 does not cause susceptibility to systemic lupus erythematosus. Arthritis Rheum 1987;30:961–966.

    Article  PubMed  CAS  Google Scholar 

  45. Waxman FJ, Hebert LA, Cornacoff JB, Van Aman ME, Swead WL, Krant EH, Birmingham DJ, Taguiam JM: Complement depletion accelerates the clearance of immune complexes from the circulation of primates. J Clin Invest 1984;74: 1329–1340.

    Article  PubMed  CAS  Google Scholar 

  46. Dykman TR, Hatch JA, Atkinson JP: Polymorphism of the human C3b/C4b receptor: Identification of a third allele and analysis of receptor phenotypes in families and patients with systemic lupus erythematosus. J Exp Med 1984;159:691–703.

    Article  PubMed  CAS  Google Scholar 

  47. Cornillet P, Gredy P, Pannaforte JL, Meyer O, Kazatchkine MD, Cohen JHM: Increased frequency of the long (S) allotype of CR1 (the C3b/C4b receptor, CD35) in patients with systemic lupus erythematosus. Clin Exp Immunol 1992;89:22–25.

    PubMed  CAS  Google Scholar 

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Kumar, A., Malaviya, A.N., Sinha, S. et al. C3b receptor (CR1) genomic polymorphism in rheumatoid arthritis. Immunol Res 13, 61–71 (1994). https://doi.org/10.1007/BF02918226

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