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病程，以III类和IV类肾炎、灾难性抗磷脂综合征、严重血液学畸变或血管炎为特征，表现为复发性神经功能缺损、肺实质疾病或心肌炎。 这部分患者目前接受高剂量糖皮质激素或环磷酰胺的重复治疗。 SLE的特征是自身耐受性的持续丧失，在一个免疫抑制过程后抗自身抗体复发。 来自因恶性肿瘤接受骨髓移植的免疫性疾病个体的反应的轶事证据表明，移植后发生的免疫重建可以随着获得对自身抗原的新耐受而发生。 在免疫消融后，在没有任何先前激发抗原刺激的情况下，允许免疫系统从干细胞祖细胞重建自身，可以允许免疫疾病的延长缓解。先前成功的环磷酰胺治疗，给予更温和的剂量，在减少器官威胁和危及生命的表现狼疮，使其成为一个合乎逻辑的选择免疫消融治疗。 使用抗胸腺球蛋白联合环磷酰胺治疗应延长CD 4/CD 8细胞的逆转，这通常是骨髓消融后一年免疫重建的特征。 希望这种情况有助于延长对自身抗原的耐受性。通过疾病活动的血清学和临床参数，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 paitents 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.