Abstract
The goal of autologous peripheral blood stem cell transplantation (PBSCT) in autoimmune diseases is to ablate the clones of autoimmune lymphocytes. We evaluated the T-cell repertoire in 5 patients (pts) with systemic sclerosis (SSc) who received T-depleted (mean T-cell reduction, 5.2 log) autologous PBSCT after a conditioning regimen of cyclophosphamide (200–400 mg/m2/day x 5), fludarabine (25 mg/m2/day x 5), and rabbit anti-thymocyte globulin (2.5 mg/kg/day x 3). One pt has had a recurrence of SSc at 12 months after PBSCT; the other pts are progression-free at 4.9+, 5.1+, 6.5+ and 11.5+ months, respectively, after PBSCT. We used 5-color flow cytometry to assess T-cell receptor V-beta repertoire in CD4+ and CD8+ peripheral T-cells susbsetted into central memory (CM; CD45RA−/CD27+), naïve (N, CD45RA+/CD27+), effector/memory (EM; CD45RA−/CD27−) and effector (E; CD45RA−/CD27−) populations. Pts were studied before and at 21 days after PBSCT. The pt with recurrence of SSc had 2 large expansions in CD4+ T-cells (Vbeta 1 and 14) before PBSCT, which were conserved and amplified at 21 days post PBSCT. These expansions were limited to the EM and E populations before PBSCT but were evident in all except the E subset at 21 days after PBSCT. Of the remaining 4 pts, none had evidence of CD4 expansions, and 3 had multiple CD8 expansions before PBSCT. In all cases, the expansions were limited to the EM and E populations. None of these T-cell restrictions were conserved in the 21-day post-PBSCT sample. These data suggest that EM and E T-cell expansions present before PBSCT in pts with SSc can be ablated by an immunosuppressive conditioning regimen. Although our observations require confirmation in a larger series of pts, the conservation of restrictions at 21 days after PBSCT may be a poor prognostic sign for efficacy of autologous PBSCT in SSc.
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