Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis
Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis
复制标题
DOI：
10.1016/s0140-6736(99)02429-0
复制
发表时间：
1999-11-13
期刊：
影响因子：
168.9
通讯作者：
Compston, A
中科院分区：
文献类型：
--
作者：
Coles, AJ;Wing, N;Compston, A
多发性硬化是由中枢神经系统T细胞依赖性炎性脱髓鞘引起的。我们的目标是长期抑制炎症与短期单克隆抗体treatment.Methods我们耗尽了95%的循环淋巴细胞在27例多发性硬化症患者通过5天脉冲的人源化抗CD 52单克隆抗体，Campath-1H，临床和血液学后果的T细胞耗竭，和患者外周血的体外反应，治疗后18个月对血液单核细胞进行了连续分析。结果治疗后至少18个月内，疾病活动的放射学和临床标志物显着减少。然而，三分之一的患者产生了促甲状腺激素受体抗体和卡比马唑反应性自身免疫性甲状腺功能亢进症。耗尽的外周血淋巴细胞池与细胞，减少有丝分裂原诱导的增殖和干扰素γ分泌在体外重建，解释Campath-1H导致免疫反应从Th 1表型的变化，抑制多发性硬化症疾病的活动，但允许抗体介导的甲状腺自身免疫的产生。
Background Multiple sclerosis results from T-cell-dependent inflammatory demyelination of the central nervous system. Our objective was long-term suppression of inflammation with short-term monoclonal antibody treatment.Methods We depleted 95% of circulating lymphocytes in 27 patients with multiple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclonal antibody, Campath-1H, Clinical and haematological consequences of T-cell depletion, and in-vitro responses of patients' peripheral-blood mononuclear cells were analysed serially for 18 months after treatment.Findings Radiological and clinical markers of disease activity were significantly decreased for at least 18 months after treatment. However, a third of patients developed antibodies against the thyrotropin receptor and carbimazole-responsive autoimmune hyperthyroidism. The depleted peripheral lymphocyte pool was reconstituted with cells that had decreased mitogen-induced proliferation and interferon gamma secretion in vitro,Interpretation Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.