title: Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells.
abstract: OBJECTIVE
  The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc.
  
  
  METHODS
  Eleven patients (three males and eight females) with SSc were enrolled. Blood mononuclear cells were harvested after mobilization treatment with CYC and G-CSF. CD34+ haematopoietic stem/progenitor cell fractions were purified and cryopreserved. Patients were transplanted with > 2 × 10(6)/kg autologous CD34+ cells after high-dose CYC (50 mg/kg for 4 days) conditioning. Immune reconstitution was evaluated serially by analysing lymphocyte subpopulations for 36 months.
  
  
  RESULTS
  Progressive improvement of skin sclerosis has been observed for 3 years in most of the patients. The serum level of anti-Scl-70, an auto-antibody specific to SSc, was progressively decreased after ASCT. Improvement of skin sclerosis was significantly associated with the change in the serum anti-Scl-70 level after ASCT at 36 months. Serum levels of KL-6 and surfactant protein D, indicators for interstitial pneumonia activity, were also significantly decreased. The number of CD8+ T cells immediately recovered within a month after ASCT, while the number of CD4+ T cells remained low for >36 months post-transplant. The majority of CD4+ cells were memory but not naïve T cells, and regulatory CD4+ T cells were not recovered. Th1/Th2 ratio was significantly increased after ASCT.
  
  
  CONCLUSIONS
  ASCT with purified CD34+ cells was effective in controlling the disease activity of SSc. Th1/Th2 ratio was significantly increased for at least 3 years after ASCT.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. tsukamot@intmed1.med.kyushu-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Nagafuji
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mitoma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Arinobu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kentaro
authors.initials: K
authors.lastname: To
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004264:DNA Topoisomerases, Type I; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D009687:Nuclear Proteins / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D012074:Remission Induction; D012595:Scleroderma, Systemic / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D018417:Th1 Cells / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; C060192:MUC1 protein, human; D018396:Mucin-1; D009687:Nuclear Proteins; D037663:Pulmonary Surfactant-Associated Protein D; C048100:Scl 70 antigen, human; D003520:Cyclophosphamide; D004264:DNA Topoisomerases, Type I