Rheumatology International

, Volume 26, Issue 3, pp 240–243 | Cite as

Soluble CD21 in sera and synovial fluid of arthritic patients

  • Thomas Grottenthaler
  • Johannes von Kempis
  • Sigune Goldacker
  • Harald IllgesEmail author
Original Article


Soluble CD21 (sCD21) is the ectodomain of the CD21 glycoprotein released by shedding from the cellular membrane. The ectodomain of CD21 is capable of binding complement fragments, Epstein-Barr virus (EBV) and CD23. Functionally sCD21 can activate monocytes and abrogate B-cell/follicular dendritic cell interaction, thereby inhibiting antibody production by antigen primed B cells. Levels of sCD21 vary in several clinical conditions. Here we analyzed sCD21 in synovial fluids and sera in arthritic patients. sCD21 concentrations were consistently lower in synovial fluids compared to paired sera samples from the same patients. In contrast to healthy donors, sCD21 levels are significantly reduced in rheumatoid arthritis patient’s sera. Potential causes and consequences of the data are discussed.


Complement receptor 2 Shedding CD21 Arthritis Synovial fluid 



This work was supported by the Hans-Hench-Stiftung, the Thurgauische Stiftung für Wissenschaft und Forschung through the Kanton Thurgau and the Bundesamt für Bildung und Wissenschaft (BBW), Bern, Switzerland through grant QLG1-CT-2001-01536 to HI.


  1. 1.
    Corr M, Firestein GS (2002) Innate immunity as a hired gun: but is it rheumatoid arthritis? J Exp Med 195:F33–F35CrossRefPubMedGoogle Scholar
  2. 2.
    Feldmann M, Brennan FM, Maini RN (1996) Rheumatoid arthritis. Cell 85:307–310CrossRefPubMedGoogle Scholar
  3. 3.
    Harris EDJ (1997) Rheumatoid arthritis, 1 edn. W.B.Saunders, CaliforniaGoogle Scholar
  4. 4.
    Mollnes TE, Lea T, Mellbye OJ, Pahle J, Grand O, Harboe M (1986) Complement activation in rheumatoid arthritis evaluated by C3dg and the terminal complement complex. Arthritis Rheum 29:715–721PubMedGoogle Scholar
  5. 5.
    Heaney ML, Golde DW (1998) Soluble receptors in human disease. J Leukoc Biol 64:135–146PubMedGoogle Scholar
  6. 6.
    Dello SP, Rovida E (2002) Transmodulation of cell surface regulatory molecules via ectodomain shedding. Biol Chem 383:69–83CrossRefPubMedGoogle Scholar
  7. 7.
    Fearon DT, Carroll MC (2000) Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol 18:393–422CrossRefPubMedGoogle Scholar
  8. 8.
    Ling NR, Brown B (1992) Properties of soluble CR2 in human serum. Immunobiology 185:403–414PubMedGoogle Scholar
  9. 9.
    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 93:195–199PubMedGoogle Scholar
  10. 10.
    Fremeaux-Bacchi V, Aubry JP, Bonnefoy JY, Kazatchkine MD, Kolb JP, Fischer EM (1998) Soluble CD21 induces activation and differentiation of human monocytes through binding to membrane CD23. Eur J Immunol 28:4268–4274Google Scholar
  11. 11.
    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 161:4549–4554Google Scholar
  12. 12.
    Fremeaux-Bacchi V, Kolb JP, Rakotobe S, Kazatchkine MD, Fischer EM (1999) Functional properties of soluble CD21. Immunopharmacology 42:31–37Google Scholar
  13. 13.
    Illges H, Braun M, Peter HH, Melchers I (2000) Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes. Clin Exp Immunol 122:270–276CrossRefPubMedGoogle Scholar
  14. 14.
    Masilamani M, Seydlitz EV, Bastmeyer M, Illges H (2002) T cell activation induced by cross-linking CD3 and CD28 receptors leads to silencing of Epstein-Barr virus/C3d receptor (CR2/CD21) gene and protein expression. Immunobiology 206:528–536PubMedGoogle Scholar
  15. 15.
    Masilamani M, Nowack R, Witte T, Schlesier M, Warnatz K, Glocker MO, Peter HH, Illges H (2004) Reduction of Soluble Complement Receptor II/CD21 in Systemic Lupus Erythomatosus and Sjoegren’s Syndrome but not Juvenile Arthritis. Scand J Immunol (in press)Google Scholar
  16. 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) 43:186–190Google Scholar
  17. 17.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedGoogle Scholar
  18. 18.
    Cronstein BN, Eberle MA, Gruber HE, Levin RI (1991) Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A 88:2441–2445Google Scholar
  19. 19.
    Gu B, Bendall LJ, Wiley JS (1998) Adenosine triphosphate-induced shedding of CD23 and L-selectin (CD62L) from lymphocytes is mediated by the same receptor but different metalloproteases. Blood 92:946–951PubMedGoogle Scholar
  20. 20.
    Papiha SS, Pal B, Walker D, Mangion P, Hossain MA (1989) Alpha 1 antitrypsin (PI) phenotypes in two rheumatic diseases: a reappraisal of the association of PI subtypes in rheumatoid arthritis. Ann Rheum Dis 48:48–52PubMedGoogle Scholar
  21. 21.
    Reparon-Schuijt CC, van Esch WJ, van Kooten C, Levarht EW, Breedveld FC, Verweij CL (1998) Functional analysis of rheumatoid factor-producing B cells from the synovial fluid of rheumatoid arthritis patients. Arthritis Rheum 41:2211–2220Google Scholar
  22. 22.
    Masilamani M, Kassahn D, Mikkat S, Glocker MO, Illges H (2003) B cell activation leads to shedding of complement receptor type II (CR2/CD21). Eur J Immunol 33:2391–2397Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Thomas Grottenthaler
    • 1
  • Johannes von Kempis
    • 2
  • Sigune Goldacker
    • 3
  • Harald Illges
    • 1
    • 4
    Email author
  1. 1.Biotechnology Institute ThurgauTägerwilenSwitzerland
  2. 2.Division of Rheumatology and Clinical ImmunologyKantonsspital St.GallenSt.GallenSwitzerland
  3. 3.Division of Rheumatology and Clinical ImmunologyUniversity of Freiburg Medical CenterFreiburgGermany
  4. 4.Department of Natural SciencesUniversity of Applied SciencesRheinbachGermany

Personalised recommendations