title: Immunological reconstitution after autologous hematopoietic stem cell transplantation in patients with systemic sclerosis: relationship between clinical benefits and intensity of immunosuppression.
abstract: OBJECTIVE
  To analyze the relationship between clinical benefits and immunological changes in patients with systemic sclerosis (SSc) treated with autologous hematopoietic stem cell transplantation (HSCT).
  
  
  METHODS
  Ten patients with SSc were treated with high-dose cyclophosphamide followed by highly purified CD34+ cells (n=5) or unpurified grafts (n=5). Two groups of patients were retrospectively constituted based on their clinical response (good responders, n=7; and poor responders, n=3). As well as clinical findings, immunological reconstitution through autologous HSCT was assessed by fluorescence-activated cell sorter analysis, quantification of signal joint T cell receptor rearrangement excision circles (sjTREC), reflecting the thymic function, and foxp3, a key gene of regulatory T cells, mRNA levels.
  
  
  RESULTS
  Patients' clinical and immunological findings were similar between good and poor responders, or CD34-purified and unpurified groups at inclusion. The sjTREC values were significantly suppressed at 3 months after autologous HSCT in good responders compared with poor responders (p=0.0152). Reconstitution of CD4+CD45RO- naive T cells was delayed in good responders compared with poor responders. The phenotype of other lymphocytes, cytokine production in T cells, and foxp3 gene expression levels after autologous HSCT did not correlate with clinical response in good or poor responders. Clinical and immunological findings after autologous HSCT were similar between CD34-purified and unpurified groups.
  
  
  CONCLUSIONS
  Our results suggest that immunosuppression intensity, sufficient to induce transient suppression of thymic function, is attributable to the feasible clinical response in patients with SSc treated with autologous HSCT. Appropriate monitoring of sjTREC values may predict clinical benefits in transplanted SSc patients after autologous HSCT.
authors.affiliation: Department of Medicine II, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Bohgaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Bohgaki
authors.forename: Akira
authors.initials: A
authors.lastname: Furusaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kondo
authors.forename: Kazuko C
authors.initials: KC
authors.lastname: Sato-Matsumura
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kataoka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horita
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yasuda
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Amasaki
authors.forename: Mitsufumi
authors.initials: M
authors.lastname: Nishio
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Sawada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery*; D019172:Transplantation Conditioning / Q000379:methods*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide