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Blood, 1 January 2009, Vol. 113, No. 1, pp. 214-223. Prepublished online as a Blood First Edition Paper on September 29, 2008; DOI 10.1182/blood-2008-07-168286. This Article Full Text (PDF) All Versions of this Article: blood-2008-07-168286v1 113/1/214    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Alexander, T. Articles by Hiepe, F. Search for Related Content PubMed PubMed Citation Articles by Alexander, T. Articles by Hiepe, F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 14, 2008 Accepted August 15, 2008 Depletion of autoreactive immunological memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system Tobias Alexander*, Andreas Thiel, Oliver Rosen, Gero Massenkeil, Arne Sattler, Siegfried Kohler, Henrik Mei, Hartmut Radtke, Erika Gromnica-Ihle, Gerd-Rudiger Burmester, Renate Arnold, Andreas Radbruch, and Falk Hiepe German Rheumatism Research Center, Berlin, Germany Regenerative Immunology and Aging, Berlin-Brandenberg Center for Regenerative Therapies (BCRT), Berlin, Germany Department of Hematology and Oncology, Charite Universitatsmedizin, Berlin, Germany Institute for Transfusion Medicine, Charite Universitatsmedizin, Berlin, Germany Rheuma-Klinik Berlin-Buch, Berlin, Germany Department of Rheumatology and Clinical Immunology, Charite Universitatsmedizin, Berlin, Germany * Corresponding author; email: tobias.alexander{at}charite.de. Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce long-term clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution following ASCT in seven adult patients with SLE. The long-term clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-dsDNA antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31+ CD45RA+ CD4+ T cells (recent thymic emigrants) with a doubling in absolute numbers compared to age-matched healthy controls at the 3yr-follow-up (p=0.016), the regeneration of thymic-derived FoxP3+ regulatory T cells, and normalization of peripheral TCR repertoire usage. In a similar manner, responders exhibited normalization of the previously disturbed B cell homeostasis with numeric recovery of the naive B cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to re-establish self-tolerance in SLE. Our clinical trial is registered at www.clinicaltrials.gov under the ID NCT00742300. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Resetting the clock Gabor G. Illei Blood 2009 113: 2-3. [Full Text] [PDF]

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