Abstract
Systemic lupus erythematosus (SLE) is a common autoimmune disease with complex etiology. Recently, a possible role of apoptotic cells in its pathogenesis has been suggested. This study is to evaluate the expression of Fas antigen on peripheral blood lymphocytes (PBLs) in SLE, to determine whether membrane Fas (mFas) has a role in the organ damage in SLE and to explore its relationship with the early apoptosis of the PBLs in SLE. Flow cytometry was used to evaluate the expression of mFas on PBLs in 68 Chinese SLE patients and 37 healthy controls. Systemic lupus international collaborative clinics/american colleges of rheumatology damage index (SDI) scores were calculated to further estimate the relationship of the expression of mFas with disease severity. Results showed that mFas expression levels were significantly higher (P < 0.01) among SLE patients than those in healthy controls. Higher (P = 0.01) expressions of mFas were found in patients with SDI scores ≥ as compared to those with SDI scores <3. Patients with neuropsychiatric or renal disease had a higher expression of mFas than those without neuropsychiatric (P = 0.03) or renal disease (P = 0.01). In addition, the expression levels had a positive (r = 0.381, P < 0.01) correlation with the early apoptosis rate of PBLs in SLE patients. Taken together, our study showed that Fas-expressing PBLs were increased in SLE patients, especially in patients with higher SDI score, and the expression levels of mFas were correlated to the organ damage and lymphocytes apoptosis.
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Gladman DD, Urowitz MB, Rahman P, Ibanez D, Tam LS (2003) Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol 30:1955–1959
Kaplan MJ (2004) Apoptosis in systemic lupus erythematosus. Clin Immunol 112:210–218. doi:10.1016/j.clim.2004.04.007
Sheriff A, Gaipl US, Voll RE, Kalden JR, Herrmann M (2004) Apoptosis and systemic lupus erythematosus. Rheum Dis Clin North Am 30:505–527, viii–ix. doi:10.1016/j.rdc.2004.04.006
White S, Rosen A (2003) Apoptosis in systemic lupus erythematosus. Curr Opin Rheumatol 15:557–562. doi:10.1097/00002281-200309000-00006
Huggins ML, Todd I, Cavers MA, Pavuluri SR, Tighe PJ, Powell RJ (1999) Antibodies from systemic lupus erythematosus (sle) sera define differential release of autoantigens from cell lines undergoing apoptosis. Clin Exp Immunol 118:322–328. doi:10.1046/j.1365-2249.1999.01063.x
Silva LM, Garcia AB, Donadi EA (2002) Increased lymphocyte death by neglect-apoptosis is associated with lymphopenia and autoantibodies in lupus patients presenting with neuropsychiatric manifestations. J Neurol 249:1048–1054. doi:10.1007/s00415-002-0781-6
Bijl M, Horst G, Limburg PC, Kallenberg CG (2001) Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (sle): relation to lymphocyte activation and disease activity. Lupus 10:866–872. doi:10.1191/096120301701548517
Berden JH (2003) Lupus nephritis: consequence of disturbed removal of apoptotic cells? Neth J Med 61:233–238
Kuenkele S, Beyer TD, Voll RE, Kalden JR, Herrmann M (2003) Impaired clearance of apoptotic cells in systemic lupus erythematosus: challenge of t and b cell tolerance. Curr Rheumatol Rep 5:175–177. doi:10.1007/s11926-003-0061-1
Bijl M, van Lopik T, Limburg PC, Spronk PE, Jaegers SM, Aarden LA, Smeenk RJ, Kallenberg GG (1998) Do elevated levels of serum-soluble fas contribute to the persistence of activated lymphocytes in systemic lupus erythematosus? J Autoimmun 11:457–463. doi:10.1006/jaut.1998.0233
Timmer T, de Vries EG, de Jong S (2002) Fas receptor-mediated apoptosis: a clinical application? J Pathol 196:125–134. doi:10.1002/path.1028
Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ (2002) Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419:395–399. doi:10.1038/nature01063
Eneslatt K, Rantapaa-Dahlqvist S, Uddhammar A, Sundqvist KG (2001) The regulation of fasl expression—a distinquishing feature between monocytes and t lymphocytes/nk cells with possible implications for sle. J Clin Immunol 21:183–192. doi:10.1023/A:1011035115342
Hochberg MC (1997) Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725. doi:10.1002/art.1780400928
Ren Y, Tang J, Mok MY, Chan AW, Wu A, Lau CS (2003) Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus. Arthritis Rheum 48:2888–2897. doi:10.1002/art.11237
Borgerson KL, Bretz JD, Baker JR Jr (1999) The role of fas-mediated apoptosis in thyroid autoimmune disease. Autoimmunity 30:251–264
Salmaso C, Bagnasco M, Pesce G, Montagna P, Brizzolara R, Altrinetti V, Richiusa P, Galluzzo A, Giordano C (2002) Regulation of apoptosis in endocrine autoimmunity: insights from Hashimoto’s thyroiditis and Graves’ disease. Ann N Y Acad Sci 966:496–501
Nose M, Nishihara M, Kamogawa J, Terada M, Nakatsuru S (2000) Genetic basis of autoimmune disease in mrl/lpr mice: dissection of the complex pathological manifestations and their susceptibility loci. Rev Immunogenet 2:154–164
Theofilopoulos AN, Kono DH (1999) The genes of systemic autoimmunity. Proc Assoc Am Physicians 111:228–240. doi:10.1046/j.1525-1381.1999.99244.x
Silvestris F, Grinello D, Tucci M, Cafforio P, Dammacco F (2003) Enhancement of t cell apoptosis correlates with increased serum levels of soluble fas (cd95/apo-1) in active lupus. Lupus 12:8–14. doi:10.1191/0961203303lu250oa
Hao JH, Ye DQ, Zhang GQ, Liu HH, Dai H, Huang F, Pan FM, Su H, Dong MX, Chen H, Wang Q, Zhang XJ (2006) Elevated levels of serum soluble fas are associated with organ and tissue damage in systemic lupus erythematosus among chinese. Arch Dermatol Res 297:329–332. doi:10.1007/s00403-005-0616-2
Neff TA, Guo RF, Neff SB, Sarma JV, Speyer CL, Gao H, Bernacki KD, Huber-Lang M, McGuire S, Hoesel LM, Riedemann NC, Beck-Schimmer B, Zetoune FS, Ward PA (2005) Relationship of acute lung inflammatory injury to fas/fasl system. Am J Pathol 166:685–694
Xue C, Lan-Lan W, Bei C, Jie C, Wei-Hua F (2006) Abnormal fas/fasl and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus. Cell Immunol 239:121–128. doi:10.1016/j.cellimm.2006.05.003
Drappa J, Brot N, Elkon KB (1993) The fas protein is expressed at high levels on cd4+ cd8+ thymocytes and activated mature lymphocytes in normal mice but not in the lupus-prone strain, mrl lpr/lpr. Proc Natl Acad Sci USA 90:10340–10344. doi:10.1073/pnas.90.21.10340
Fathi NA, Hussein MR, Hassan HI, Mosad E, Galal H, Afifi NA (2006) Glomerular expression and elevated serum bcl-2 and fas proteins in lupus nephritis: preliminary findings. Clin Exp Immunol 146:339–343. doi:10.1111/j.1365-2249.2006.03219.x
Courtney PA, Crockard AD, Williamson K, McConnell J, Kennedy RJ, Bell AL (1999) Lymphocyte apoptosis in systemic lupus erythematosus: relationships with fas expression, serum soluble fas and disease activity. Lupus 8:508–513. doi:10.1191/096120399678840765
Yonehara S (2002) Death receptor fas and autoimmune disease: from the original generation to therapeutic application of agonistic anti-fas monoclonal antibody. Cytokine Growth Factor Rev 13:393–402. doi:10.1016/S1359-6101(02)00024-2
Bijl M, Horst G, Limburg PC, Kallenberg CG (2001) Anti-cd3-induced and anti-fas-induced apoptosis in systemic lupus erythematosus (sle). Clin Exp Immunol 123:127–132. doi:10.1046/j.1365-2249.2001.01418.x
Albert ML (2004) Death-defying immunity: do apoptotic cells influence antigen processing and presentation? Nat Rev Immunol 4:223–231. doi:10.1038/nri11308
Lorenz HM, Herrmann M, Winkler T, Gaipl U, Kalden JR (2000) Role of apoptosis in autoimmunity. Apoptosis 5:443–449. doi:10.1023/A:1009692902805
Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (30571608, 30771848), the Natural Science Foundation of Anhui Province (070413109) and the Specialized Research Fund for the Doctoral Program of Higher Education (20070366002). We are grateful to the subjects who participated in this study. We express our thanks to the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital, for their supports.
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Li, LH., Li, WX., Wu, O. et al. Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus: relation to the organ damage and lymphocytes apoptosis. Mol Biol Rep 36, 2047–2052 (2009). https://doi.org/10.1007/s11033-008-9415-0
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DOI: https://doi.org/10.1007/s11033-008-9415-0