Immunological reconstitution after autologous hematopoietic stem cell transplantation in patients with systemic sclerosis: relationship between clinical benefits and intensity of immunosuppression.
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.
Bohgaki
Toshiyuki
T
Department of Medicine II, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo 060-8638, Japan.
Atsumi
Tatsuya
T
Bohgaki
Miyuki
M
Furusaki
Akira
A
Kondo
Makoto
M
Sato-Matsumura
Kazuko C
KC
Abe
Riichiro
R
Kataoka
Hiroshi
H
Horita
Tetsuya
T
Yasuda
Shinsuke
S
Amasaki
Yoshiharu
Y
Nishio
Mitsufumi
M
Sawada
Ken-Ichi
K
Shimizu
Hiroshi
H
Koike
Takao
T
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
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide