Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1988 Apr;72(1):74–78.

The rate of loss of CR1 from ageing erythrocytes in vivo in normal subjects and SLE patients: no correlation with structural or numerical polymorphisms.

F Moldenhauer 1, M Botto 1, M J Walport 1
PMCID: PMC1541491  PMID: 2899464

Abstract

The stability of CR1 (complement receptor type 1) on ageing erythrocytes in vivo was examined in a group of normal subjects who had been genotyped using a restriction fragment length polymorphism (detected using a cDNA probe for CR1) that correlates with the numerical expression of CR1 on normal erythrocytes (H = allele correlating with high expression, L = low). Erythrocytes were separated into 5 fractions of increasing age on discontinuous Percoll gradients. Mean CR1 numbers on erythrocytes fell from 636 molecules per cell in the first fraction to 384 in the fifth in the HH group and from 478 to 315 in the LL group. There was no difference in the rate of decline of CR1 numbers between the groups. A group of nine SLE patients was also studied in the same way; their genotypes were HH (four) and HL (five). Mean CR1 numbers amongst all of these patients fell from 477 to 232, a faster rate of decline than in a genotypically matched group of normal subjects. There was no difference in the prevalence of the different structural allotypes amongst 30 SLE patients compared with 21 normal subjects. These data provide further evidence that there are enhanced extracellular mechanisms for the removal of CR1 from erythrocytes of SLE patients and do not support the hypothesis that inherited variation in CR1 expression on erythrocytes increases disease susceptibility to SLE.

Full text

PDF
75

Selected References

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

  1. Brok F., Ramot B., Zwang E., Danon D. Enzyme activities in human red blood cells of different age groups. Isr J Med Sci. 1966 May-Jun;2(3):291–296. [PubMed] [Google Scholar]
  2. Cornacoff J. B., Hebert L. A., Smead W. L., VanAman M. E., Birmingham D. J., Waxman F. J. Primate erythrocyte-immune complex-clearing mechanism. J Clin Invest. 1983 Feb;71(2):236–247. doi: 10.1172/JCI110764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dykman T. R., Cole J. L., Iida K., Atkinson J. P. Polymorphism of human erythrocyte C3b/C4b receptor. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1698–1702. doi: 10.1073/pnas.80.6.1698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dykman T. R., Hatch J. A., Aqua M. S., Atkinson J. P. Polymorphism of the C3b/C4b receptor (CR1): characterization of a fourth allele. J Immunol. 1985 Mar;134(3):1787–1789. [PubMed] [Google Scholar]
  5. Dykman T. R., Hatch J. A., Atkinson J. P. 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 Mar 1;159(3):691–703. doi: 10.1084/jem.159.3.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Holme E., Fyfe A., Zoma A., Veitch J., Hunter J., Whaley K. Decreased C3b receptors (CR1) on erythrocytes from patients with systemic lupus erythematosus. Clin Exp Immunol. 1986 Jan;63(1):41–48. [PMC free article] [PubMed] [Google Scholar]
  7. Iida K., Mornaghi R., Nussenzweig V. Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus. J Exp Med. 1982 May 1;155(5):1427–1438. doi: 10.1084/jem.155.5.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KLOPSTOCK A., SCHWARTZ J., BLEIBERG Y., ADAM A., SZEINBERG A. HEREDITARY NATURE OF THE BEHAVIOUR OF ERYTHROCYTES IN THE IMMUNE ADHERENCE HAEMAGGLUTINATION PHENOMENON. Vox Sang. 1965 Mar-Apr;10:177–187. doi: 10.1111/j.1423-0410.1965.tb04335.x. [DOI] [PubMed] [Google Scholar]
  9. Klickstein L. B., Wong W. W., Smith J. A., Weis J. H., Wilson J. G., Fearon D. T. Human C3b/C4b receptor (CR1). Demonstration of long homologous repeating domains that are composed of the short consensus repeats characteristics of C3/C4 binding proteins. J Exp Med. 1987 Apr 1;165(4):1095–1112. doi: 10.1084/jem.165.4.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kulczycki A., Jr, Krause V., Killion C. C., Atkinson J. P. Improved cell surface radioiodination of macrophages. J Immunol Methods. 1980;37(2):133–138. doi: 10.1016/0022-1759(80)90198-2. [DOI] [PubMed] [Google Scholar]
  11. Lachmann P. J., Walport M. J. Deficiency of the effector mechanisms of the immune response and autoimmunity. Ciba Found Symp. 1987;129:149–171. doi: 10.1002/9780470513484.ch11. [DOI] [PubMed] [Google Scholar]
  12. Medof M. E., Iida K., Mold C., Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes. J Exp Med. 1982 Dec 1;156(6):1739–1754. doi: 10.1084/jem.156.6.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Piomelli S., Corash L. M., Davenport D. D., Miraglia J., Amorosi E. L. In vivo lability of glucose-6-phosphate dehydrogenase in GdA- and GdMediterranean deficiency. J Clin Invest. 1968 Apr;47(4):940–948. doi: 10.1172/JCI105786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ripoche J., Sim R. B. Loss of complement receptor type 1 (CR1) on ageing of erythrocytes. Studies of proteolytic release of the receptor. Biochem J. 1986 May 1;235(3):815–821. doi: 10.1042/bj2350815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ross G. D., Lambris J. D., Cain J. A., Newman S. L. Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs CR1 cofactor activity. J Immunol. 1982 Nov;129(5):2051–2060. [PubMed] [Google Scholar]
  16. Ross G. D., Medof M. E. Membrane complement receptors specific for bound fragments of C3. Adv Immunol. 1985;37:217–267. doi: 10.1016/s0065-2776(08)60341-7. [DOI] [PubMed] [Google Scholar]
  17. Ross G. D., Yount W. J., Walport M. J., Winfield J. B., Parker C. J., Fuller C. R., Taylor R. P., Myones B. L., Lachmann P. J. Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. J Immunol. 1985 Sep;135(3):2005–2014. [PubMed] [Google Scholar]
  18. Salvo G., Caprari P., Samoggia P., Mariani G., Salvati A. M. Human erythrocyte separation according to age on a discontinuous "Percoll" density gradient. Clin Chim Acta. 1982 Jul 1;122(2):293–300. doi: 10.1016/0009-8981(82)90290-x. [DOI] [PubMed] [Google Scholar]
  19. Seya T., Holers V. M., Atkinson J. P. Purification and functional analysis of the polymorphic variants of the C3b/C4b receptor (CR1) and comparison with H, C4b-binding protein (C4bp), and decay accelerating factor (DAF). J Immunol. 1985 Oct;135(4):2661–2667. [PubMed] [Google Scholar]
  20. The diet and all-causes death rate in the Seven Countries Study. Lancet. 1981 Jul 11;2(8237):58–61. [PubMed] [Google Scholar]
  21. Uko G., Dawkins R. L., Kay P., Christiansen F. T., Hollingsworth P. N. CR1 deficiency in SLE: acquired or genetic? Clin Exp Immunol. 1985 Nov;62(2):329–336. [PMC free article] [PubMed] [Google Scholar]
  22. Van Dyne S., Holers V. M., Lublin D. M., Atkinson J. P. The polymorphism of the C3b/C4b receptor in the normal population and in patients with systemic lupus erythematosus. Clin Exp Immunol. 1987 Jun;68(3):570–579. [PMC free article] [PubMed] [Google Scholar]
  23. Walport M. J., Lachmann P. J. Erythrocyte complement receptor type 1, immune complexes, and the rheumatic diseases. Arthritis Rheum. 1988 Feb;31(2):153–158. doi: 10.1002/art.1780310201. [DOI] [PubMed] [Google Scholar]
  24. Walport M. J., Ross G. D., Mackworth-Young C., Watson J. V., Hogg N., Lachmann P. J. Family studies of erythrocyte complement receptor type 1 levels: reduced levels in patients with SLE are acquired, not inherited. Clin Exp Immunol. 1985 Mar;59(3):547–554. [PMC free article] [PubMed] [Google Scholar]
  25. Walport M., Ng Y. C., Lachmann P. J. Erythrocytes transfused into patients with SLE and haemolytic anaemia lose complement receptor type 1 from their cell surface. Clin Exp Immunol. 1987 Sep;69(3):501–507. [PMC free article] [PubMed] [Google Scholar]
  26. Waxman F. J., Hebert L. A., Cornacoff J. B., VanAman M. E., Smead W. L., Kraut E. H., Birmingham D. J., Taguiam J. M. Complement depletion accelerates the clearance of immune complexes from the circulation of primates. J Clin Invest. 1984 Oct;74(4):1329–1340. doi: 10.1172/JCI111543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Waxman F. J., Hebert L. A., Cosio F. G., Smead W. L., VanAman M. E., Taguiam J. M., Birmingham D. J. Differential binding of immunoglobulin A and immunoglobulin G1 immune complexes to primate erythrocytes in vivo. Immunoglobulin A immune complexes bind less well to erythrocytes and are preferentially deposited in glomeruli. J Clin Invest. 1986 Jan;77(1):82–89. doi: 10.1172/JCI112306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilson J. G., Murphy E. E., Wong W. W., Klickstein L. B., Weis J. H., Fearon D. T. Identification of a restriction fragment length polymorphism by a CR1 cDNA that correlates with the number of CR1 on erythrocytes. J Exp Med. 1986 Jul 1;164(1):50–59. doi: 10.1084/jem.164.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wilson J. G., Wong W. W., Schur P. H., Fearon D. T. Mode of inheritance of decreased C3b receptors on erythrocytes of patients with systemic lupus erythematosus. N Engl J Med. 1982 Oct 14;307(16):981–986. doi: 10.1056/NEJM198210143071604. [DOI] [PubMed] [Google Scholar]
  30. Wong W. W., Kennedy C. A., Bonaccio E. T., Wilson J. G., Klickstein L. B., Weis J. H., Fearon D. T. Analysis of multiple restriction fragment length polymorphisms of the gene for the human complement receptor type I. Duplication of genomic sequences occurs in association with a high molecular mass receptor allotype. J Exp Med. 1986 Nov 1;164(5):1531–1546. doi: 10.1084/jem.164.5.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wong W. W., Wilson J. G., Fearon D. T. Genetic regulation of a structural polymorphism of human C3b receptor. J Clin Invest. 1983 Aug;72(2):685–693. doi: 10.1172/JCI111018. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES