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Establishment of juvenile and tolerant immune systems in patients with autoimmune diseases treated with immunoablation and autologous stem cell therapy

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Immunoablation (i.e. complete destruction of a patient's autoreactive immune system) in combination with autologous stem cell transplantation (ASCT) is used for treatment of severe autoimmune diseases. If successful, the patients will undergo long-term remission. We have analysed reconstitution of the immune system in such patients, to determine whether it recovers by expansion of surviving lymphocytes or develops from stem cells de novo. During a follow-up period of up to 60 months after ASCT, one polychondritis patient and two systemic lupus erythematosus patients in clinical remission were analysed for reappearance of naïve, activated and memory B lymphocytes and T lymphocytes, for reactivity against pathogens and autoantigens, and for presence of autoantibodies. Titers of disease-specific autoantibodies decreased after ASCT with the half-life of secreted antibodies, and did not reappear. Naive T cells and naive B cells reappeared and reached normal levels within several months after ASCT. The repertoire of the naive T cells was not restricted. The numbers and frequencies of recent thymic emigrants (CD31+/CD45RA+/CD4+), marked by expression of T-cell receptor recombination excision circles, equalled those of cord blood and were considerably higher than in normal probands of the age of the patients. Thus, the thymus is reactivated and the reconstituted immune system rejuvenated and tolerized in those patients. The immunological memory has to be and is indeed generated de novo.

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  • Systemic Lupus Erythematosus
  • Cord Blood
  • Systemic Lupus Erythematosus Patient
  • Clinical Remission
  • Autologous Stem Cell Transplantation