IMMUNE ABLATION AND HEMATOPOIETIC STEM CELL SUPPORT IN PATIENTS WITH SLE

Northwestern University, Evanston IL

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Abstract

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.