RT Journal Article
SR Electronic
T1 Immunological Reconstitution after Autologous Hematopoietic Stem Cell Transplantation in Patients with Systemic Sclerosis: Relationship Between Clinical Benefits and Intensity of Immunosuppression
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1240
OP 1248
DO 10.3899/jrheum.081025
VO 36
IS 6
A1 TOSHIYUKI BOHGAKI
A1 TATSUYA ATSUMI
A1 MIYUKI BOHGAKI
A1 AKIRA FURUSAKI
A1 MAKOTO KONDO
A1 KAZUKO C. SATO-MATSUMURA
A1 RIICHIRO ABE
A1 HIROSHI KATAOKA
A1 TETSUYA HORITA
A1 SHINSUKE YASUDA
A1 YOSHIHARU AMASAKI
A1 MITSUFUMI NISHIO
A1 KEN-ICHI SAWADA
A1 HIROSHI SHIMIZU
A1 TAKAO KOIKE
YR 2009
UL http://www.jrheum.org/content/36/6/1240.abstract
AB 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.