IMMUNE ABLATION AND HEMATOPOIETIC STEM CELL SUPPORT IN PATIENTS WITH SLE

系统性红斑狼疮在少数患者中表现为侵袭性的病程，以III级和IV级肾炎、灾难性的抗磷脂综合征、严重的血液系统紊乱或血管炎为特征，表现为反复出现的神经功能障碍、肺实质疾病或心肌炎。这部分患者目前正在接受大剂量糖皮质激素或环磷酰胺的反复疗程治疗。系统性红斑狼疮的特点是持续的自我耐受性丧失的本质，即在免疫抑制病程后抗自身抗体复发。来自免疫性疾病患者因恶性肿瘤接受骨髓移植后的反应的轶事证据表明，移植后发生的免疫重建可能伴随着对自身抗原的新耐受性的获得。在没有任何先前激发的抗原刺激的情况下，允许免疫系统在免疫消融后从干细胞前体细胞重建自身，可能会延长免疫性疾病的缓解时间。环磷酰胺治疗在减少威胁器官和生命的狼疮症状方面取得了先前的成功，给药剂量较适中，使其成为免疫消融治疗的合理选择。联合使用抗胸腺细胞球蛋白和环磷酰胺治疗可以延长CD4/CD8细胞的倒置，这通常是骨髓消融后一年免疫重建的特征。人们希望这种情况将有助于延长自身抗原的耐受期。通过血清学和疾病活动性的临床参数，应该可以监测这种耐受性的持久性。

Systemic lupus erythematosus pursues an aggressive course in a minority of patients, marked by Class III and Class IV nephritis, catastrophic anti-phospholipid syndrome, severe hematologic aberrations, or vasculitis, manifested by recurrent neurologic deficits, pulmonary parenchymal disease, or myocarditis. This subset of patients currently is treated with repeated courses of high dose glucocorticoids or cyclophosphamide. It is the nature of the persistent loss of self-tolerance that characterizes SLE that anti-self antibodies recur after a course of immunosuppression. Anecdotal evidence, derived from the responses of individuals with immunologic diseases who have received bone marrow transplantation for malignancy, suggests that the immune reconsistitution that occurs after transplantation can occur with acquisition of new tolerance to self-antigens. To allow the immune system to reconstitute itself from the stem cell progenitor after immune ablation, in the absence of any previously inciting antigenic stimulus, may allow extended remission from immunologic disease. The prior success of cyclophosphamide therapy, given in more moderate dosage, in curtailing organ-threatening and life-threatening manifestations of lupus, makes it a logical choice for immune ablation therapy. The use of anti-thymocite globulin in conjunction with cyclophosphamide therapy should prolong the inversion of CD4/CD8 cells, which normally characterizes immune reconstitution for a year after marrow ablation. It is hoped that a prolonged tolerance of self-antigens will be facilitated by this condition. By serologic as well as clinical parameters of disease activity, it should be possible to monitor the durability of this tolerance.