Document Detail

Immunological reconstitution after autologous hematopoietic stem cell transplantation in patients with systemic sclerosis: relationship between clinical benefits and intensity of immunosuppression.
MedLine Citation:
PMID:  19447934     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
Toshiyuki Bohgaki; Tatsuya Atsumi; Miyuki Bohgaki; Akira Furusaki; Makoto Kondo; Kazuko C Sato-Matsumura; Riichiro Abe; Hiroshi Kataoka; Tetsuya Horita; Shinsuke Yasuda; Yoshiharu Amasaki; Mitsufumi Nishio; Ken-Ichi Sawada; Hiroshi Shimizu; Takao Koike
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-15
Journal Detail:
Title:  The Journal of rheumatology     Volume:  36     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-10     Completed Date:  2009-08-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1240-8     Citation Subset:  IM    
Department of Medicine II, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo 060-8638, Japan.
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MeSH Terms
Bone Marrow Transplantation*
Cyclophosphamide / therapeutic use
Drug Therapy, Combination
Granulocyte Colony Stimulating Factor, Recombinant / pharmacology
Hematopoietic Stem Cell Transplantation*
Immunocompromised Host
Immunosuppressive Agents / therapeutic use
Middle Aged
Scleroderma, Systemic / drug therapy,  immunology*,  surgery*
Transplantation Conditioning / methods*
Young Adult
Reg. No./Substance:
0/Granulocyte Colony Stimulating Factor, Recombinant; 0/Immunosuppressive Agents; 50-18-0/Cyclophosphamide

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