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Systemic reduction of soluble complement receptor II/CD21 during pregnancy to levels reminiscent of autoimmune disease

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Abstract

Complement receptor type II/CD21 is the functional receptor for complement fragments such as C3d, iC3b and the Epstein Barr Virus. A soluble form of CD21 (sCD21) is shed from lymphocytes surface and is able to bind to its ligands found in the plasma. The amount of sCD21 in serum may modulate immunity as the plasma levels are correlated with autoimmune conditions, such as Systemic Lupus Erythematosus, Rheumatoid Arthritis and Sjoegren’s Syndrome. Because of the fact that pregnancy may lead to remission of autoimmune diseases we determined the serum levels of sCD21 during pregnancy and postpartum. The serum sCD21 levels during pregnancy are significantly lower as compared to that of the healthy controls. There were no significant differences in sCD21 levels between the mother and the cord blood also immediately after parturition. Restoration of sCD21 levels to normal values takes between 6 weeks and 1 year after childbirth. Our study indicates that CD21-shedding is affected during pregnancy comparable to that of autoimmunity.

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References

  1. Myones BL, Ross GD (1987) Identification of a spontaneously shed fragment of B cell complement receptor type two (CR2) containing the C3d-binding site. Complement 4:87–98

    PubMed  CAS  Google Scholar 

  2. Ling N, Hansel T, Richardson P, Brown B (1991) Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia. Clin Exp Immunol 84:16–22

    PubMed  CAS  Google Scholar 

  3. Huemer HP, Larcher C, Prodinger WM, Petzer AL, Mitterer M, Falser N (1993) Determination of soluble CD21 as a parameter of B cell activation. Clin Exp Immunol 93:195–199

    PubMed  CAS  Google Scholar 

  4. Masilamani M, Kassahn D, Mikkat S, Glocker M, Illges H (2003) B cell activation leads to shedding of complement receptor type II (CR2/CD21). Eur J Immunol 33:2382–2390

    Article  Google Scholar 

  5. Ostensen M, Villiger PM (2002) Immunology of pregnancy-pregnancy as a remission inducing agent in rheumatoid arthritis. Transpl Immunol 9:155–160

    Article  PubMed  CAS  Google Scholar 

  6. Ostensen M, von Esebeck M, Villiger PM (2007) Therapy with immunosuppressive drugs and biological agents and use of contraception in patients with rheumatic disease. J Rheumatol 34:1266–1269

    PubMed  Google Scholar 

  7. Tedder TF, Clement LT, Cooper MD (1984) Expression of C3d receptors during human B cell differentiation: immunofluorescence analysis with the HB–5 monoclonal antibody. J Immunol 133:678–683

    PubMed  CAS  Google Scholar 

  8. Schwab J, Illges H (2001) Regulation of CD21 expression by DNA methylation and histone deacetylation. Int Immunol 13:705–710

    Article  PubMed  CAS  Google Scholar 

  9. Fischer E, Delibrias C, Kazatchkine MD (1991) Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes. J Immunol 146:865–869

    PubMed  CAS  Google Scholar 

  10. Masilamani M, von Seydlitz E, Bastmeyer M, Illges H (2002) T cell activation induced by cross-linking CD3 and CD28 leads to silencing of Epstein-Barr virus/C3d receptor (CR2/CD21) gene and protein expression. Immunobiology 206:528–536

    Article  PubMed  CAS  Google Scholar 

  11. Larcher C, Schulz TF, Hofbauer J, Hengster P, Romani N, Wachter H, Dierich MP (1990) Expression of the C3d/EBV receptor and of other cell membrane surface markers is altered upon HIV–1 infection of myeloid, T, and B cells. J Acquir Immune Defic Syndr 3:103–108

    PubMed  CAS  Google Scholar 

  12. Delibrias CC, Fischer E, Bismuth G, Kazatchkine MD (1992) Expression, molecular association, and functions of C3 complement receptors CR1 (CD35) and CR2 (CD21) on the human T cell line HPB-ALL. J Immunol 149:768–774

    PubMed  CAS  Google Scholar 

  13. Carroll MC, Prodeus AP (1998) Linkages of innate and adaptive immunity. Curr Opin Immunol 10:36–40

    Article  PubMed  CAS  Google Scholar 

  14. Lowe J, Brown B, Hardie D, Richardson P, Ling N (1989) Soluble forms of CD21 and CD23 antigens in the serum in B cell chronic lymphocytic leukaemia. Immunol Lett 20:103–109

    Article  PubMed  CAS  Google Scholar 

  15. Masilamani M, Nowack R, Witte T, Schlesier M, Warnatz K, Glocker MO, Peter HH, Illges H (2004) Reduction of soluble complement receptor 2/CD21 in systemic lupus erythomatosus and Sjogren’s syndrome but not juvenile arthritis. Scand J Immunol 60(6):625–630

    Google Scholar 

  16. Masilamani M, von Kempis J, Illges H (2004) Decreased levels of serum soluble complement receptor-II (CR2/CD21) in patients with rheumatoid arthritis. Rheumatology (Oxford) 43:186–190

    Article  CAS  Google Scholar 

  17. Masilamani M, Apell H, Illges H (2002) Purification and characterization of soluble CD21 from human plasma by affinity chromatography and density gradient centrifugation. J Immunol Methods 270:11

    PubMed  CAS  Google Scholar 

  18. Aichem A, Masilamani M, Illges H (2006) Redox regulation of CD21 shedding involves signaling via PKC and indicates the formation of a juxtamembrane stalk. J Cell Sci 119:2892–2902

    Article  PubMed  CAS  Google Scholar 

  19. Qin D, Wu J, Carroll MC, Burton GF, Szakal AK, Tew JG (1998) Evidence for an important interaction between a complement-derived CD21 ligand on follicular dendritic cells and CD21 on B cells in the initiation of IgG responses. J Immunol 161:4549–4554

    PubMed  CAS  Google Scholar 

  20. Fremeaux-Bacchi V, Kolb JP, Rakotobe S, Kazatchkine MD, Fischer EM (1999) Functional properties of soluble CD21. Immunopharmacology 42:31–37

    Article  PubMed  CAS  Google Scholar 

  21. Xu C, Mao D, Holers VM, Palanca B, Cheng AM, Molina H (2000) A critical role for murine complement regulator crry in fetomaternal tolerance. Science 287:498–501

    Article  PubMed  CAS  Google Scholar 

  22. Grottenthaler T, von Kempis J, Goldacker S, Illges H (2006) Soluble CD21 in sera and synovial fluid of arthritic patients. Rheumatol Int 26(3):240–243

    Google Scholar 

  23. Nicholas NS, Panayi GS, Nouri AM (1984) Human pregnancy serum inhibits interleukin–2 production. Clin Exp Immunol 58:587–595

    PubMed  CAS  Google Scholar 

  24. Holland D, Bretscher P, Russell AS (1984) Immunologic and inflammatory responses during pregnancy. J Clin Lab Immunol 14:177–179

    PubMed  CAS  Google Scholar 

  25. Griffioen AW, Franklin SW, Zegers BJ, Rijkers GT (1993) Expression and functional characteristics of the complement receptor type 2 on adult and neonatal B lymphocytes. Clin Immunol Immunopathol 69:1–8

    Article  PubMed  CAS  Google Scholar 

  26. Timens W, Boes A, Rozeboom-Uiterwijk T, Poppema S (1989) Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. J Immunol 143:3200–3206

    PubMed  CAS  Google Scholar 

  27. Rijkers GT, Sanders EA, Breukels MA, Zegers BJ (1998) Infant B cell responses to polysaccharide determinants. Vaccine 16:1396–1400

    Article  PubMed  CAS  Google Scholar 

  28. Pabst HF, Kreth HW (1980) Ontogeny of the immune response as a basis of childhood disease. J Pediatr 97:519–534

    Article  PubMed  CAS  Google Scholar 

  29. Prodeus AP, Goerg S, Shen LM, Pozdnyakova OO, Chu L, Alicot EM, Goodnow CC, Carroll MC (1998) A critical role for complement in maintenance of self-tolerance. Immunity 9:721–731

    Article  PubMed  CAS  Google Scholar 

  30. Boackle SA, Holers VM, Chen X, Szakonyi G, Karp DR, Wakeland EK, Morel L (2001) Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15:775–785

    Article  PubMed  CAS  Google Scholar 

  31. Carter RH, Fearon DT (1992) CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256:105–107

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Drs. Biegert, Brunner and Balig for sera. This work was supported by AUTOROME European Community grant no. LSHM-CT-2004-005264 to HI.

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Authors and Affiliations

  1. Division of Pediatric Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, 10029, USA

    Madhan Masilamani

  2. Department of Natural Sciences, Immunology and Cell Biology, University of Applied Sciences Bonn-Rhein-Sieg, von-Liebig-Str. 20, 53359, Rheinbach, Germany

    Narendiran Rajasekaran, Anjana Singh, Hui-Zhi Low, Kerstin Albus, Swantje Anders, Frank Behne, Peter Eiermann, Katharina König, Clarissa Mindnich, Teodora Ribarska & Harald Illges

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  1. Madhan Masilamani
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Correspondence to Harald Illges.

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Masilamani, M., Rajasekaran, N., Singh, A. et al. Systemic reduction of soluble complement receptor II/CD21 during pregnancy to levels reminiscent of autoimmune disease. Rheumatol Int 28, 1137–1141 (2008). https://doi.org/10.1007/s00296-008-0604-x

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  • DOI: https://doi.org/10.1007/s00296-008-0604-x

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