Autologous stem cell tranplantation (ASCT) in refractory autoimmune disease: Reconstitution of the immune system without relapse of disease

Journal/Book: Z Rheumatol 1999; 58 Suppl. 1: I/28 (FE 27). 1999;

Abstract: 1Deutsches Rheuma-Forschungszentrum; 2Universitätsklinikum Charité Berlin; 3Rheumaklinik Berlin-Buch High dose ablative chemotherapy followed by autologous transplantation of highly purified CD34+ cells is currently being evaluated as a new strategy for the treatment of severe autoimmune disease. We report here on 5 patients who received highly purified autologous CD34' cells for severe therapy refraetory autoimmune disease. Peripheral blood CD34+ cells were isolated using the CliniMACS separation device. CD3+ cells were below 1.5 *104/kg in all transplants. With a follow up of 12-4 months 4 patients are in clinical and serological remission and no disease activity could be observed. Absolute counts of CD19+ B cells CD4+ T cells and CD8+ T cells reached pre-transplantation status in these patients after 4-7 months. While the majority of reconstituting B cells consist of naive IgD+ B cells Th cells detectable during the early phase of immune reconstitution (<6 months after ASCT) almost exclusively were of memory/effector type. High frequencies of these cells were activated characterised by expression of HLA-DR. Naive Th cells could be detected in these patients in low frequencies only after 4-6 months thereafter continuously increasing in frequencies and absolute counts. One patient with systemic sclerosis presented no changes of the clinical situation. Lymphoid reconstitution in this patient was fast within 4 weeks after ASCT. We conclude that in successfully treated patients the immune sytem had been generated de novo and is tolerant to rheumatic autoantigens while "old" autoreactive cells have been eliminated effeciently. le

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