Journal
RHEUMATOLOGY
Volume 50, Issue 5, Pages 944-952Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keq414
Keywords
Autoimmune disease; High-dose cyclophosphamide; Transplantation; Immune reconstitution; Th1; Th2 balance
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Funding
- Ministry of Health, Labor and Welfare [H22-Immunity-Ippan-008]
- Ministry of Education, Science, Sports and Culture of Japan [21591266]
- Grants-in-Aid for Scientific Research [21591267, 21591266] Funding Source: KAKEN
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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.
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