RA治疗新进展(2)
(三)造血干细胞移植(HSCT)
应用大剂量免疫抑制剂及造血干细胞移植治疗自身免疫性疾病成为目前研究的热点，且已在系统性红斑狼疮的治疗上取得了较为肯定的疗效(8)。一般认为其机理包括两方面：首先，大剂量免疫抑制剂的应用对自身免疫病起到了缓解作用；其次，HSCT后约半年开始免疫重建，包括细胞免疫和体液免疫重建、CD4/CD8淋巴细胞比例的倒置、自然抑制细胞的增多及T细胞池的改变等，可以认为是其治疗自身免疫病并使其长期缓解的主要机理。具体方法主要是先用CTX 2g/m2及G-CSF行干细胞动员，然后采集干细胞并行CD34+细胞分选，再予CTX200mg/kg、ATG、甲基强的松龙行预处理，最后行干细胞回输。美国、英国分别于近期报道以此方法进行的小样本RA(分别为4例和8例)的临床研究未取得实质性进展(9、10)。考虑在以后的研究中，可在病例选择、免疫抑制剂应用剂量、是否同时联合DMARDs或CyA治疗及移植物的处理等方面作进一步探讨。
, 百拇医药
总之，RA的发病机理至今尚无定论，但这并不意味着人们对RA的治疗束手无策。目前研究的作用于T细胞细胞因子等的生物治疗及基因治疗成为绕过致病的始动因素的新途径，造血干细胞移植也越来越有希望成为人们攻克RA治疗难题的金钥匙。这些新方法将成为RA治疗中的里程碑，具有重要的临床应用前景。
参考文献
1.Choy EHS, Pitzalis C, Cauli A, et al. Percentage of anti-CD4 monoclonal antibody-coated lymphocytes in the rheumatoid joints is associated with clinical improvement: Implications for the development of immunotheraputic dosing regiments. Arthritis Rheum 1996; 39: 52-6.
, 百拇医药
2.Moreland LW, Pratt PW, Mayes MD, et al. Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 antibody, CM-T412, in rheumatoid arthritis patients receiving concomitant methotrexate. Arthritis Rheum 1995; 38:1581-8.
3.Moreland LW, Heck LW, Koopman WJ, et al. VB17 T cell receptor peptide vaccine in rheumatoid arthritis: results of a phase I dose escalation study. J Rheumatol 1996, 23: 1353-62.
4.Campion LW, lebasack ME, lookabaugh J, et al. Dose-range and dose-frequency study of recombinent human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. Arthritis Rheum 1996, 39: 1092-101.
, 百拇医药
5.Elliott MJ, Maini RN, Foldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to TNF-a. Arthritis Rheum 1993, 21: 318-27.
6.Otani K, Nita I, Macaulay W. Suppression of antigen-induced arthritis in rabbits by ex/vivo gene therapy. J Immunol 1996, 156: 3558-62.
7.Evans CH, Robbins PD, Ghivizzani SC, et al. Clinical trial to assess the safe feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 1996, 7: 1261-80.
, 百拇医药
8.Traynor AE, Schroeder J, Rosa M, et al. Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study. Lancet 2000, 356: 701-7.
9.Burt RK, Georganas C, Schroeder J, et al. Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis. Arthritis Rheum 1999, 42: 2281-5.
10.Snowden JA, Biggs JC, Milliken ST, et al. A phase I/II dose escalation study of intensified cyclophosphamide and autologous blood stem cell rescue in severe, active theumatiod arthritis. Arthritis Rheum 1999, 42: 2286-92., 百拇医药(董怡)
应用大剂量免疫抑制剂及造血干细胞移植治疗自身免疫性疾病成为目前研究的热点，且已在系统性红斑狼疮的治疗上取得了较为肯定的疗效(8)。一般认为其机理包括两方面：首先，大剂量免疫抑制剂的应用对自身免疫病起到了缓解作用；其次，HSCT后约半年开始免疫重建，包括细胞免疫和体液免疫重建、CD4/CD8淋巴细胞比例的倒置、自然抑制细胞的增多及T细胞池的改变等，可以认为是其治疗自身免疫病并使其长期缓解的主要机理。具体方法主要是先用CTX 2g/m2及G-CSF行干细胞动员，然后采集干细胞并行CD34+细胞分选，再予CTX200mg/kg、ATG、甲基强的松龙行预处理，最后行干细胞回输。美国、英国分别于近期报道以此方法进行的小样本RA(分别为4例和8例)的临床研究未取得实质性进展(9、10)。考虑在以后的研究中，可在病例选择、免疫抑制剂应用剂量、是否同时联合DMARDs或CyA治疗及移植物的处理等方面作进一步探讨。
, 百拇医药
总之，RA的发病机理至今尚无定论，但这并不意味着人们对RA的治疗束手无策。目前研究的作用于T细胞细胞因子等的生物治疗及基因治疗成为绕过致病的始动因素的新途径，造血干细胞移植也越来越有希望成为人们攻克RA治疗难题的金钥匙。这些新方法将成为RA治疗中的里程碑，具有重要的临床应用前景。
参考文献
1.Choy EHS, Pitzalis C, Cauli A, et al. Percentage of anti-CD4 monoclonal antibody-coated lymphocytes in the rheumatoid joints is associated with clinical improvement: Implications for the development of immunotheraputic dosing regiments. Arthritis Rheum 1996; 39: 52-6.
, 百拇医药
2.Moreland LW, Pratt PW, Mayes MD, et al. Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 antibody, CM-T412, in rheumatoid arthritis patients receiving concomitant methotrexate. Arthritis Rheum 1995; 38:1581-8.
3.Moreland LW, Heck LW, Koopman WJ, et al. VB17 T cell receptor peptide vaccine in rheumatoid arthritis: results of a phase I dose escalation study. J Rheumatol 1996, 23: 1353-62.
4.Campion LW, lebasack ME, lookabaugh J, et al. Dose-range and dose-frequency study of recombinent human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. Arthritis Rheum 1996, 39: 1092-101.
, 百拇医药
5.Elliott MJ, Maini RN, Foldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to TNF-a. Arthritis Rheum 1993, 21: 318-27.
6.Otani K, Nita I, Macaulay W. Suppression of antigen-induced arthritis in rabbits by ex/vivo gene therapy. J Immunol 1996, 156: 3558-62.
7.Evans CH, Robbins PD, Ghivizzani SC, et al. Clinical trial to assess the safe feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 1996, 7: 1261-80.
, 百拇医药
8.Traynor AE, Schroeder J, Rosa M, et al. Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study. Lancet 2000, 356: 701-7.
9.Burt RK, Georganas C, Schroeder J, et al. Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis. Arthritis Rheum 1999, 42: 2281-5.
10.Snowden JA, Biggs JC, Milliken ST, et al. A phase I/II dose escalation study of intensified cyclophosphamide and autologous blood stem cell rescue in severe, active theumatiod arthritis. Arthritis Rheum 1999, 42: 2286-92., 百拇医药(董怡)