Analysis of immune reconstitution after autologous CD34(+) stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4(+) T cells

作者：Tsukamoto Hiroshi^*; Nagafuji Koji; Horiuchi Takahiko; Mitoma Hiroki; Niiro Hiroaki; Arinobu Yojiro; Inoue Yasushi; To Kentaro; Miyamoto Toshihiro; Iwasaki Hiromi; Teshima Takanori; Harada Mine; Akashi Koichi

来源：Rheumatology, 2011, 50(5): 944-952.

DOI：10.1093/rheumatology/keq414

• Autoimmune disease
• High-dose cyclophosphamide
• Transplantation
• Immune reconstitution
• Th1
• Th2 balance

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 x 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 naive 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.

• 出版日期2011-5