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. 2001 Mar;60(3):237–241. doi: 10.1136/ard.60.3.237

Soluble CD95 concentrations are increased in patients with severe systemic lupus erythematosus, but not in their first degree relatives

M W van der Linden 1, T van Lopik 1, L Aarden 1, R Westendorp 1, T Huizinga 1
PMCID: PMC1753586  PMID: 11171685

Abstract

OBJECTIVE—Plasma concentrations of soluble CD95 (sCD95) are raised in patients with systemic lupus erythematosus (SLE) before clinical relapses become manifest. Increased sCD95 concentrations may therefore be a familial characteristic that is associated with susceptibility to severe disease. To test this, sCD95 concentrations were measured in healthy first degree relatives of patients with severe and non-severe SLE.
METHODS—Seventy seven first degree relatives of 26 patients with severe, and 72 relatives of 25 patients with non-severe lupus were studied. Controls were 42 first degree relatives of 17 patients with chronic cutaneous lupus erythematosus (CCLE) and 63 partners of the patients with their first degree relatives. Severe lupus was defined as both multi-organ disease and cyclophosphamide treatment, non-severe lupus as neither. Organ damage was assessed with the SLICC-ACR index, disease activity with SLEDAI.
RESULTS—Soluble CD95 concentrations in relatives of patients with severe SLE were similar to those in relatives of patients with non-severe SLE, relatives of patients with CCLE, and controls (median (interquartile range) sCD95 concentration 0.59 (0.52-0.66) v 0.57 (0.50-0.63), 0.56 (0.51-0.71), and 0.55 (0.49-0.61) ng/ml, p=0.25, p=0.94, and p=0.17, respectively). Increased concentrations of sCD95, however, were found in patients with severe SLE compared with those in patients with non-severe SLE, patients with CCLE, and control relatives (0.77 (0.70-0.97) v 0.60 (0.54-0.67), 0.57 (0.54-0.71), and 0.57 (0.52-0.63) ng/ml, respectively, p<0.001). Concentrations of sCD95 were significantly correlated with damage index scores (rs=0.47, p<0.01). Basic and clinical characteristics of patients with SLE, including SLEDAI scores, could not explain these observations.
CONCLUSION—Soluble CD95 concentrations are associated with severity of the disease and not with susceptibility for severe SLE.



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Selected References

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  1. Al-Maini M. H., Mountz J. D., Al-Mohri H. A., El-Ageb E. M., Al-Riyami B. M., Svenson K. L., Zhou T., Richens E. R. Serum levels of soluble Fas correlate with indices of organ damage in systemic lupus erythematosus. Lupus. 2000;9(2):132–139. doi: 10.1191/096120300678828145. [DOI] [PubMed] [Google Scholar]
  2. Arnett F. C., Hamilton R. G., Reveille J. D., Bias W. B., Harley J. B., Reichlin M. Genetic studies of Ro (SS-A) and La (SS-B) autoantibodies in families with systemic lupus erythematosus and primary Sjögren's syndrome. Arthritis Rheum. 1989 Apr;32(4):413–419. doi: 10.1002/anr.1780320410. [DOI] [PubMed] [Google Scholar]
  3. Arnett F. C., Reveille J. D. Genetics of systemic lupus erythematosus. Rheum Dis Clin North Am. 1992 Nov;18(4):865–892. [PubMed] [Google Scholar]
  4. Aupeix K., Hugel B., Martin T., Bischoff P., Lill H., Pasquali J. L., Freyssinet J. M. The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J Clin Invest. 1997 Apr 1;99(7):1546–1554. doi: 10.1172/JCI119317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bijl M., van Lopik T., Limburg P. C., Spronk P. E., Jaegers S. M., Aarden L. A., Smeenk R. J., Kallenberg G. G. Do elevated levels of serum-soluble fas contribute to the persistence of activated lymphocytes in systemic lupus erythematosus? J Autoimmun. 1998 Oct;11(5):457–463. doi: 10.1006/jaut.1998.0233. [DOI] [PubMed] [Google Scholar]
  6. Bombardier C., Gladman D. D., Urowitz M. B., Caron D., Chang C. H. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992 Jun;35(6):630–640. doi: 10.1002/art.1780350606. [DOI] [PubMed] [Google Scholar]
  7. Cascino I., Fiucci G., Papoff G., Ruberti G. Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. J Immunol. 1995 Mar 15;154(6):2706–2713. [PubMed] [Google Scholar]
  8. Chan O. T., Madaio M. P., Shlomchik M. J. The central and multiple roles of B cells in lupus pathogenesis. Immunol Rev. 1999 Jun;169:107–121. doi: 10.1111/j.1600-065x.1999.tb01310.x. [DOI] [PubMed] [Google Scholar]
  9. Cheng J., Zhou T., Liu C., Shapiro J. P., Brauer M. J., Kiefer M. C., Barr P. J., Mountz J. D. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994 Mar 25;263(5154):1759–1762. doi: 10.1126/science.7510905. [DOI] [PubMed] [Google Scholar]
  10. Drappa J., Vaishnaw A. K., Sullivan K. E., Chu J. L., Elkon K. B. Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Engl J Med. 1996 Nov 28;335(22):1643–1649. doi: 10.1056/NEJM199611283352204. [DOI] [PubMed] [Google Scholar]
  11. Elkon K. B. Apoptosis in SLE--too little or too much? Clin Exp Rheumatol. 1994 Sep-Oct;12(5):553–559. [PubMed] [Google Scholar]
  12. Freedman B. I., Wilson C. H., Spray B. J., Tuttle A. B., Olorenshaw I. M., Kammer G. M. Familial clustering of end-stage renal disease in blacks with lupus nephritis. Am J Kidney Dis. 1997 May;29(5):729–732. doi: 10.1016/s0272-6386(97)90126-8. [DOI] [PubMed] [Google Scholar]
  13. Georgescu L., Vakkalanka R. K., Elkon K. B., Crow M. K. Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand. J Clin Invest. 1997 Nov 15;100(10):2622–2633. doi: 10.1172/JCI119806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ginzler E. M., Diamond H. S., Weiner M., Schlesinger M., Fries J. F., Wasner C., Medsger T. A., Jr, Ziegler G., Klippel J. H., Hadler N. M. A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis. Arthritis Rheum. 1982 Jun;25(6):601–611. doi: 10.1002/art.1780250601. [DOI] [PubMed] [Google Scholar]
  15. Gladman D., Ginzler E., Goldsmith C., Fortin P., Liang M., Urowitz M., Bacon P., Bombardieri S., Hanly J., Hay E. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996 Mar;39(3):363–369. doi: 10.1002/art.1780390303. [DOI] [PubMed] [Google Scholar]
  16. Goel N., Ulrich D. T., St Clair E. W., Fleming J. A., Lynch D. H., Seldin M. F. Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease. Arthritis Rheum. 1995 Dec;38(12):1738–1743. doi: 10.1002/art.1780381206. [DOI] [PubMed] [Google Scholar]
  17. Huggins M. L., Todd I., Cavers M. A., Pavuluri S. R., Tighe P. J., Powell R. J. Antibodies from systemic lupus erythematosus (SLE) sera define differential release of autoantigens from cell lines undergoing apoptosis. Clin Exp Immunol. 1999 Nov;118(2):322–328. doi: 10.1046/j.1365-2249.1999.01063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Knipping E., Krammer P. H., Onel K. B., Lehman T. J., Mysler E., Elkon K. B. Levels of soluble Fas/APO-1/CD95 in systemic lupus erythematosus and juvenile rheumatoid arthritis. Arthritis Rheum. 1995 Dec;38(12):1735–1737. doi: 10.1002/art.1780381205. [DOI] [PubMed] [Google Scholar]
  19. Lippman S. M., Arnett F. C., Conley C. L., Ness P. M., Meyers D. A., Bias W. B. Genetic factors predisposing to autoimmune diseases. Autoimmune hemolytic anemia, chronic thrombocytopenic purpura, and systemic lupus erythematosus. Am J Med. 1982 Dec;73(6):827–840. doi: 10.1016/0002-9343(82)90773-2. [DOI] [PubMed] [Google Scholar]
  20. Mountz J. D., Zhou T., Cheng J. Use of sensitive assays to detect soluble Fas in patients with systemic lupus erythematosus: comment on the article by Knipping et al and the article by Goel et al. Arthritis Rheum. 1996 Sep;39(9):1611–1612. doi: 10.1002/art.1780390925. [DOI] [PubMed] [Google Scholar]
  21. Papoff G., Cascino I., Eramo A., Starace G., Lynch D. H., Ruberti G. An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents cell death in vitro. J Immunol. 1996 Jun 15;156(12):4622–4630. [PubMed] [Google Scholar]
  22. Rose L. M., Latchman D. S., Isenberg D. A. Elevated soluble fas production in SLE correlates with HLA status not with disease activity. Lupus. 1997;6(9):717–722. doi: 10.1177/096120339700600907. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Tokano Y., Miyake S., Kayagaki N., Nozawa K., Morimoto S., Azuma M., Yagita H., Takasaki Y., Okumura K., Hashimoto H. Soluble Fas molecule in the serum of patients with systemic lupus erythematosus. J Clin Immunol. 1996 Sep;16(5):261–265. doi: 10.1007/BF01541390. [DOI] [PubMed] [Google Scholar]
  25. Utz P. J., Hottelet M., Schur P. H., Anderson P. Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med. 1997 Mar 3;185(5):843–854. doi: 10.1084/jem.185.5.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van Lopik T., Bijl M., Hart M., Boeije L., Gesner T., Creasy A. A., Kallenberg C. G., Aarden L. A., Smeenk R. J. Patients with systemic lupus erythematosus with high plasma levels of sFas risk relapse. J Rheumatol. 1999 Jan;26(1):60–67. [PubMed] [Google Scholar]

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