Analysis of immune reconstitution after autologous CD34 + stem/progenitor cell transplantation for systemic sclerosis: Predominant reconstitution of Th1 CD4 + t cells

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

研究成果: ジャーナルへの寄稿記事

34 引用 (Scopus)

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Objective: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc. 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 × 10/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 naïve 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.

元の言語英語
記事番号keq414
ページ(範囲)944-952
ページ数9
ジャーナルRheumatology
50
発行部数5
DOI
出版物ステータス出版済み - 5 1 2011

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Systemic Scleroderma
Hematopoietic Stem Cell Transplantation
Stem Cell Transplantation
Stem Cells
Sclerosis
Hematopoietic Stem Cells
T-Lymphocytes
Serum
Pulmonary Surfactant-Associated Protein D
Skin
Interstitial Lung Diseases
Lymphocyte Subsets
Granulocyte Colony-Stimulating Factor
Regulatory T-Lymphocytes
Blood Cells
Transplants
Antibodies
Therapeutics

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

これを引用

Analysis of immune reconstitution after autologous CD34 + stem/progenitor cell transplantation for systemic sclerosis : Predominant reconstitution of Th1 CD4 + t cells. / 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.

:: Rheumatology, 巻 50, 番号 5, keq414, 01.05.2011, p. 944-952.

研究成果: ジャーナルへの寄稿記事

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title = "Analysis of immune reconstitution after autologous CD34 + stem/progenitor cell transplantation for systemic sclerosis: Predominant reconstitution of Th1 CD4 + t cells",
abstract = "Objective: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc. 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 × 10/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 na{\"i}ve 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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TY - JOUR

T1 - Analysis of immune reconstitution after autologous CD34 + stem/progenitor cell transplantation for systemic sclerosis

T2 - Predominant reconstitution of Th1 CD4 + t cells

AU - Tsukamoto, Hiroshi

AU - Nagafuji, Koji

AU - Horiuchi, Takahiko

AU - Mitoma, Hiroki

AU - Niiro, Hiroaki

AU - Arinobu, Yojiro

AU - Inoue, Yasushi

AU - To, Kentaro

AU - Miyamoto, Toshihiro

AU - Iwasaki, Hiromi

AU - Teshima, Takanori

AU - Harada, Mine

AU - Akashi, Koichi

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Objective: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc. 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 × 10/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 naïve 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.

AB - Objective: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc. 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 × 10/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 naïve 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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U2 - 10.1093/rheumatology/keq414

DO - 10.1093/rheumatology/keq414

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JO - Rheumatology

JF - Rheumatology

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