RA治療新進(jìn)展(2)
(三)造血干細(xì)胞移植(HSCT)
應(yīng)用大劑量免疫抑制劑及造血干細(xì)胞移植治療自身免疫性疾病成為目前研究的熱點(diǎn)，且已在系統(tǒng)性紅斑狼瘡的治療上取得了較為肯定的療效(8)。一般認(rèn)為其機(jī)理包括兩方面：首先，大劑量免疫抑制劑的應(yīng)用對自身免疫病起到了緩解作用；其次，HSCT后約半年開始免疫重建，包括細(xì)胞免疫和體液免疫重建、CD4/CD8淋巴細(xì)胞比例的倒置、自然抑制細(xì)胞的增多及T細(xì)胞池的改變等，可以認(rèn)為是其治療自身免疫病并使其長期緩解的主要機(jī)理。具體方法主要是先用CTX 2g/m2及G-CSF行干細(xì)胞動(dòng)員，然后采集干細(xì)胞并行CD34+細(xì)胞分選，再予CTX200mg/kg、ATG、甲基強(qiáng)的松龍行預(yù)處理，最后行干細(xì)胞回輸。美國、英國分別于近期報(bào)道以此方法進(jìn)行的小樣本RA(分別為4例和8例)的臨床研究未取得實(shí)質(zhì)性進(jìn)展(9、10)�？紤]在以后的研究中，可在病例選擇、免疫抑制劑應(yīng)用劑量、是否同時(shí)聯(lián)合DMARDs或CyA治療及移植物的處理等方面作進(jìn)一步探討。
, 百拇醫(yī)藥
總之，RA的發(fā)病機(jī)理至今尚無定論，但這并不意味著人們對RA的治療束手無策。目前研究的作用于T細(xì)胞細(xì)胞因子等的生物治療及基因治療成為繞過致病的始動(dòng)因素的新途徑，造血干細(xì)胞移植也越來越有希望成為人們攻克RA治療難題的金鑰匙。這些新方法將成為RA治療中的里程碑，具有重要的臨床應(yīng)用前景。
參考文獻(xiàn)
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.
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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., 百拇醫(yī)藥(董怡)
應(yīng)用大劑量免疫抑制劑及造血干細(xì)胞移植治療自身免疫性疾病成為目前研究的熱點(diǎn)，且已在系統(tǒng)性紅斑狼瘡的治療上取得了較為肯定的療效(8)。一般認(rèn)為其機(jī)理包括兩方面：首先，大劑量免疫抑制劑的應(yīng)用對自身免疫病起到了緩解作用；其次，HSCT后約半年開始免疫重建，包括細(xì)胞免疫和體液免疫重建、CD4/CD8淋巴細(xì)胞比例的倒置、自然抑制細(xì)胞的增多及T細(xì)胞池的改變等，可以認(rèn)為是其治療自身免疫病并使其長期緩解的主要機(jī)理。具體方法主要是先用CTX 2g/m2及G-CSF行干細(xì)胞動(dòng)員，然后采集干細(xì)胞并行CD34+細(xì)胞分選，再予CTX200mg/kg、ATG、甲基強(qiáng)的松龍行預(yù)處理，最后行干細(xì)胞回輸。美國、英國分別于近期報(bào)道以此方法進(jìn)行的小樣本RA(分別為4例和8例)的臨床研究未取得實(shí)質(zhì)性進(jìn)展(9、10)�？紤]在以后的研究中，可在病例選擇、免疫抑制劑應(yīng)用劑量、是否同時(shí)聯(lián)合DMARDs或CyA治療及移植物的處理等方面作進(jìn)一步探討。
, 百拇醫(yī)藥
總之，RA的發(fā)病機(jī)理至今尚無定論，但這并不意味著人們對RA的治療束手無策。目前研究的作用于T細(xì)胞細(xì)胞因子等的生物治療及基因治療成為繞過致病的始動(dòng)因素的新途徑，造血干細(xì)胞移植也越來越有希望成為人們攻克RA治療難題的金鑰匙。這些新方法將成為RA治療中的里程碑，具有重要的臨床應(yīng)用前景。
參考文獻(xiàn)
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.
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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.
, 百拇醫(yī)藥
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., 百拇醫(yī)藥(董怡)
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