Immunoablation in combination with autologous stem cell transplantation (ASCT) is used as a therapy for severe autoimmune diseases. We have analysed reconstitution of the immune system in patients treated with ASCT.
During a follow-up period of up to 42 months after ASCT, one polychondritis and two systemic lupus erythematosus (SLE) patients in clinical remission were analysed for reappearance of naive, activated and memory B 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. NaiveT and naive Bcells reappeared and reached normal levels within one year after ASCT. T cells activated and expanded by pathogens were easily detectable, but not T cells reacting to any of an array of autoantigens tested, in a cytometric cytokine provocation test. A third SLE patient suffered from a relapse of disease after being free of any clinical and serological symptoms for 17 months. In this patient, autoantibodies with old (anti-dsDNA antibodies) and new specificities (anti-Sm and anti-U1RNP antibodies) appeared upon relapse. A sudden decrease of peripheral naive and increase of peripheral memory B and Th cells preceeded the relapse.
ASCT for autoimmune diseases can result in longlasting remissions. According to frequencies and phenotypes of naive lymphocytes, the reconstituted immune system resembles a 'juvenile' immune system. Our results reveal that autoreactive and plasma cells do not survive the therapy but protective immune memory has to be re-established.