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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 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 Citation Map 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 Immunobiology Transplantation Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Depletion of autoreactive immunologic 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 Alexander1,2,*, Andreas Thiel1,3,*, Oliver Rosen4, Gero Massenkeil4, Arne Sattler1, Siegfried Kohler1, Henrik Mei1,5, Hartmut Radtke5, Erika Gromnica-Ihle6, Gerd-Rüdiger Burmester2, Renate Arnold4,, Andreas Radbruch1,, and Falk Hiepe1,2, 1 German Rheumatism Research Center, Berlin; 2 Department of Rheumatology and Clinical Immunology, 3 Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies 4 Department of Hematology and Oncology and 5 Institute for Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin; and 6 Rheuma-Klinik Berlin-Buch, Berlin, Germany Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce 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 after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti–double-stranded DNA (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 with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3+ regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, 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 the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE. This trial was registered at www.clinicaltrials.gov as #NCT00742300 [ClinicalTrials.gov] . 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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