靶向DNA特异性B细胞在系统性红斑狼疮中的治疗研究进展

www.yongyao.net　　2009-8-26 10:51:42　　来源：　　责任编辑：

分享到：

4 基因治疗

基因治疗也是当前治疗SLE中的研究热点。利用CTLA- 4基因抑制T细胞活化, 从而可以间接阻抑自身反应性B细胞。有研究报道用腺病毒基因转染技术使狼疮易感鼠Fas受体水平表达增高或表达CTLA- 4Ig, 可以明显缓解小鼠的淋巴细胞增生和高球蛋白血症, 延长小鼠生存时间^{[11, 12]}。但显然其作用的靶向性不强, 而且腺病毒本身能激发宿主强的免疫应答, 这些都有待克服和完善。另外人类SLE 利用基因治疗的策略还有许多问题亟待解决, 比如SLE是一种多基因遗传病, 其易感基因目前仍无统一的认识。另外基因产物能否在体内稳定、持续地表达还不能确定。可见, 现有的治疗手段有不容忽视的局限性。在SLE的治疗过程中, 如何特异、高效地清除致病性B细胞克隆- DNA特异性B细胞, 是目前要解决的关键问题和努力方向。

参考文献:
[1] Jang YJ, Stollar BD. Anti- DNA antibodies: aspects of structure and pathogenicity[J].Cell Mol Life Sci, 2003, 60(2):309.
[2] Migliorini P, Pratesi F, Bongiorni F, et al.The targets of nephritogenic antibodies in systemicautoimmune disorders[J].Autoimmunity Reviews,2002, 1(3):168.
[3] Criscione LG, Pisetsky DS. B lymphocytes and systemic lupus erythematosus[J].Curr Rheumatol Rep, 2003, 5(4): 264.
[4] Mageed RA, Prudhomme GJ. Immunopathology and the gene therapy of lupus[J].Gene Ther, 2003, 10(10):861.
[5] Fan GC, Singh RR.Vaccination with minigenes encoding V(H)- derived major histocompatibility complex class I- binding epitopes activates cytotoxic T cells that ablate autoantibody- producing B cells and inhibit lupus[J].J Exp Med, 2002, 196(6):731.
[6] Mohan C, Shi Y, Laman JD, et al. Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis[J]. J Immunol,1995, 154(3): 1470.
[7] Sfikakis PP, Via CS. Expression of CD28, CTLA4, CD80, and CD86molecules in patients with autoimmune rheumatic diseases: implications for immunotherapy[J].Clin Immunol Immunopathol, 1997, 83(3) :195.
[8] Fan GC, Singh RR.Vaccination with minigenes encoding V(H)- derived major histocompatibility complex class I- binding epitopes activates cytotoxic T cells that ablate autoantibody- producing B cells and inhibit lupus[J].J Exp Med, 2002, 196(6):731.
[9] 翟志芳, 刁庆春, 郝飞, 等. 重组嵌合毒素Dsg3EC(1- 2)PE40对寻常型天疱疮患者T、B淋巴细胞的影响[J].中华皮肤科杂志, 2005, 38(9): 536.
[10] 黄文广, 罗威, 黄汉菊, 等. 靶向DF3的白喉毒素A链基因对乳腺癌细胞的杀伤作用[J].中华实验外科杂志, 2007, 24(1):15.
[11] Hong NM, MasukoHK, Sasakawa H, et al. Amelioration of lymphoid hyperplasia and hypergammaglobulinemia in lupus2prone mice (gld) by Fas- ligand gene transfer[J].J Autoimmun, 1998, 11(4):301.
[12] Chuzhin Y, Reddy B, Budhai L, et al. Prolonged survival in murine SLE by adenoviral mediated CTLA4Ig gene transfer[J].Arthritis Rheum,1998, 41(l):140.

来源：现代医药卫生作者：杨曌王惠明

上一页 1 2