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Changes in immune cell frequencies after cyclophosphamide or mycophenolate mofetil treatments in patients with systemic lupus erythematosus
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  • 作者:Ling Zhao (1) zhaoling52@163.com
    Zhenyu Jiang (1) jiangzhenyu2012@yeah.net
    Yanfang Jiang (2) yanfangjiang@hotmail.com
    Ning Ma (1) britty1314@163.com
    Kai Wang (1) kaikai5413@sina.com
    Yandong Zhang (1) zhangyd78@sina.com
  • 关键词:Cyclophosphamide &#8211 ; Lymphocyte subsets &#8211 ; Mycophenolate mofetil &#8211 ; Systemic lupus erythematosus
  • 刊名:Clinical Rheumatology
  • 出版年:2012
  • 出版时间:June 2012
  • 年:2012
  • 卷:31
  • 期:6
  • 页码:951-959
  • 全文大小:381.9 KB
  • 参考文献:1. Delves PJ, Roitt IM (2000) The immune system: first of two parts. N Engl J Med 343:37–49
    2. Delves PJ, Roitt IM (2000) The immune system: second of two parts. N Engl J Med 343:108–117
    3. Davidson A, Diamond B (2001) Autoimmune diseases. N Engl J Med 345:340–350
    4. Adalid-Peralta L, Mathian A, Tran T et al (2008) Leukocytes and the kidney contribute to interstitial inflammation in lupus nephritis. Kidney Int 73:172–180
    5. Klinman DM, Shirai A, Ishigatsubo Y et al (1991) Quantitation of IgM- and IgG-secreting B cells in the peripheral blood of patients with systemic lupus erythematosus. Arthritis Rheum 34(11):1404–1410
    6. Portales-Perez D, Gonzalez-Amaro R, Abud-Mendoza C et al (1997) Abnormalities in CD69 expression, cytosolic pH and Ca2+ during activation of lymphocytes from patients with systemic lupus erythematosus. Lupus 6:48–56
    7. Fernandez-Gutierrez B, de Miguel S, Morado C et al (1998) Defective early T and T-dependent B cell activation in systemic lupus erythematosus. Lupus 7:314–322
    8. Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ (1999) A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J Exp Med 189:1639–1648
    9. Chan O, Shlomchik MJ (1998) A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J Immunol 160:51–59
    10. Vratsanos G, Kang I, Craft J (2001) Systemic lupus erythematosus. In: Austen KF, Frank MM, Atkinson JP, Cantor H (eds) Samter’s immunologic diseases, vol 2. Lippincott Williams & Wilkins, Philadelphia, pp 475–495
    11. Herrmann M, Voll RE, Kalden JR (2000) Etiopathogenesis of systemic lupus erythematosus. Immunol Today 21:424–426
    12. Enghard P, Humrich JY, Rudolph B, Rosenberger S, Biesen R, Kuhn A, Manz R, Hiepe F, Radbruch A, Burmester GR, Riemekasten G (2009) CXCR3+CD4+T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patients. Arthritis Rheum 60:199–206
    13. Robak E, Niewiadomska H, Robak T, Bartkowiak J, Blonski JZ, Wozniacka A, Pomorski L, Sysa-Jedrezejowska A (2001) Lymphocytes Tgammadelta in clinically normal skin and peripheral blood of patients with systemic lupus erythematosus and their correlation with disease activity. Mediators Inflamm 10:179–189
    14. Park YW, Kee SJ, Cho YN et al (2009) Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Arthritis Rheum 60:1753–1763
    15. Young-Nan Cho, Seung-Jung Kee, Sung-Ji Lee et al (2011) Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity. doi:10.1093/rheumatology/keq457
    16. Yabuhara A, Yang FC, Nakazawa T et al (1996) A killing defect of natural killer cells as an underlying immunologic abnormality in childhood systemic lupus erythematosus. J Rheumatol 23:171–177
    17. Erkeller-Y眉sel F, Hulstaart F, Hannet I et al (1993) Lymphocyte subsets in a large cohort of patients with systemic lupus erythematosus. Lupus 2:227–231
    18. Li W-X, Pan H-F, Jian-Li Hu et al (2010) Assay of T- and NK-cell subsets and the expression of NKG2A and NKG2D in patients with new-onset systemic lupus erythematosus. Clin Rheumatol 29:315–323
    19. Sibbitt WL Jr, Mathews PM, Bankhurst AD (1983) Natural killer cell in systemic lupus erythematosus: defects in effector lytic activity and response to interferon and interferon inducers. J Clin Invest 71:1230–1239
    20. Mercer JC, Ragin MJ, August A (2005) Natural killer T cells: rapid responders controlling immunity and disease. Int J Biochem Cell Biol 37:1337–1343
    21. Gapin L, Matsuda JL, Surh CD et al (2001) NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nat Immunol 2:971–978
    22. van der Vliet HJ, von Blomberg BM, Nishi N et al (2001) Circulating V(alpha24+) Vbeta11+ NKT cell numbers are decreased in a wide variety of diseases that are characterized by autoreactive tissue damage. Clin Immunol 100:144–148
    23. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
    24. Blanco P et al (2005) Increase in activated CD8+ T lymphocytes expressing perforin and granzyme B correlates with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 52:201–211
    25. Viallard JF et al (2001) HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus. Clin Exp Immunol 125:485–491
    26. Filaci G, Bacilieri S, Fravega M et al (2001) Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immunol 166(10):6452–6457
    27. Spinozzi F, Agea E, Bistoni O et al (1995) T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid-induced programmed cell death. Scand J Immunol 41:504–508
    28. Jiang M, Sun HY, Zu LP (1991) Studies on the T4+2H4+ cell of peripheral blood lymphocyte in systemic lupus erythematosus. Zhonghua Nei Ke Za Zhi 30(426–8):57
    29. Tan EM (1989) Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 44:93–151
    30. Crawford A, Macleod M, Schumacher T, Corlett L, Gray D (2006) Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol 176:3498–3506
    31. Mamula MJ, Lin RH, Janeway CA Jr, Hardin JA (1992) Breaking T cell tolerance with foreign and self coimmunogens. A study of autoimmune B and T cell epitopes of cytochrome c. J Immunol 149:789–795
    32. Greenfield EA, Nguyen KA, Kuchroo VK (1998) CD28/B7 costimulation: a review. Crit Rev Immunol 18:389–418
    33. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 2008, 9:503–510
    34. Shj FD, Wang HB, Li H et al (2000) Natural killer cells determine the outcome of B cell-mediated autoimmunity. Nat Immunol 1:245–251
    35. TakahashiK AT, Endoh M et al (2004) The regulatory role of natural killer cells in multiple sclerosis. Brain 127:1917–1927
    36. Ortaldo JR, Mason AT, O’Shea JJ (1995) Receptor-induced death in human natural killer cells: involvement of CD16. J Exp Med 181:339–344
    37. Shibatomi K, Ida H, Yamasaki S, Nakashima T, Origuchi T, Kawakami A et al (2001) A novel role for interleukin-18 in human natural killer cell death: high serum levels and low natural killer cell numbers in patients with systemic autoimmune diseases. Arthritis Rheum 44:884–892
    38. Stetson DB, Mohrs M, Reinhardt RL et al (2003) Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198:1069–1076
    39. Godfrey DI, Kronenberg M (2004) Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 114:1379–1388
    40. Kapitsinou PP, Boletis JN, Skopouli FN, Boki KA, Moutsopoulos HM (2004) Lupus nephritis: treatment with mycophenolate mofetil. Rheumatology (Oxford) 43:377–380
    41. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, Petri M, Gilkeson GS, Wallace DJ, Weisman MH, Appel GB (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 353:2219–2228
    42. Cort茅s-Hern谩ndez J, Torres-Salido MT, Medrano AS, Tarr茅s MV, Ordi-Ros J (2010) Long-term outcomes—mycophenolate mofetil treatment for lupus nephritis with addition of tacrolimus for resistant cases. Nephrol Dial Transplant 25:3939–3948
    43. Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, Li LS, Mysler E, S谩nchez-Guerrero J, Solomons N, Wofsy D, Aspreva Lupus Management Study Group (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112
  • 作者单位:1. Department of Rheumatology, First Hospital, Jilin University, Changchun, 130021 China2. Department of Central Laboratory, the Second Part of First Hospital, Jilin University, Changchun, China
  • 刊物类别:Medicine
  • 刊物主题:Medicine & Public Health
    Rheumatology
  • 出版者:Springer London
  • ISSN:1434-9949
文摘
This study was designed to explore the profile of immune cell subsets, including T, B, natural killer (NK), and NKT cells, in systemic lupus erythematosus (SLE) patients, and to determine their relationships with the clinical index and the effects of cyclophosphamide (CYC) and mycophenolate mofetil (MMF) treatment. SLE patients (n = 28) and age/sex-matched healthy controls (n = 28) were evaluated. The patients were equally divided into two treatment groups: intravenous drip (IVD) with CYC and prednisolone, and oral MMF and IVD with prednisolone. SLE peripheral blood samples were taken immediately prior to treatment and after 4 weeks of drug treatment. T, B, NK, and NKT cell subsets were measured by flow cytometry. Double-stranded DNA antibody and Sm antibody were detected by indirect immunofluorescence. Serum C3, C4, and C-reactive protein were determined by scatter turbidimetry. The percentages of CD3+CD4+ T, CD3&#8211;CD16CD56+ NK, and CD3+CD16CD56+ NKT cells and the CD4+/CD8+ ratio were significantly lower in SLE patients, while CD3+CD8+ T and CD3&#8211;CD19+ B cells were higher than the controls. The lymphocyte subsets were significantly correlated with the SLE disease activity index (SLEDAI) and complement factors (C3, C4). Four weeks of CYC or MMF treatment led to a significant increase in CD3+CD4+ T cells (P < 0.05). In addition, both CYC and MMF treatments led to increases in CD3+ T and CD3&#8211;CD16CD56+NKT cells and decreases in CD3&#8211;CD16CD56+ NK and CD3+CD8+ T cells, but these changes were not obvious. The significant correlation that exists between lymphocytes subsets and SLEDAI activity scores suggests that the lymphocyte subsets may reflect SLE severity. Our results indicate that both the traditional cyclophosphamide agent and the new mycophenolate mofetil agent can regulate the lymphocyte subsets and consequent abnormal immunity, suggesting that MMF, which is known to produce less side-effects than CYC, may be used as an effective treatment of SLE.

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