The difference of immune modification in rheumatoid arthritis patients between IL-6 blockade with tocilizumab and T cell inactivation with abatacept
| Project/Area Number |
25461481
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | Tokyo Medical University |
|---|
Principal Investigator |
MURAKAMI Miho 東京医科大学, 医学部, 助教(特任) (30595591)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIMOTO Norihiro 東京医科大学, 医学部, 兼任教授 (80273663)
松谷 隆治 和歌山県立医科大学, 医学部, 講師 (70372290)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 関節リウマチ / interleukin-6 / トシリズマブ / T細胞 / B細胞 / サイトカイン / CD4 / CD25 / Interleukin-6 / Ｔ細胞 / アバタセプト |
|---|
| Outline of Final Research Achievements |
Tocilizmab (TCZ) is a humanized anti-human IL-6 receptor antibody. We investigated whether IL-6 blockade with TCZ decreases the proportion of CD25+CD4+ T cells in ACPA positive rheumatoid arthritis (RA) patients. DAS28-ESR and SDAI were significantly reduced at 24 and 48 weeks of TCZ treatment compared with those at baseline. The proportion of CD4+ cells was significantly increased at 24 and 48 weeks compared with that at baseline. However, the proportion of CD25+CD4+ cells and that of regulatory T (Treg) cells in CD4+ cells were not significantly changed during TCZ treatment. Meanwhile, abatacept, a biologic blocking T cell co-stimulation, decreased the proportion of CD25+CD4+ T cells but not that of Treg cells in CD4+ cells in ACPA positive RA patients. In conclusions, IL-6 blockade has therapeutic effects on RA patients. Some other mechanisms, besides a decrease in CD4+ activation or an increase in Treg cell proportion, contribute the therapeutic effect of IL-6 blockade.
|
Report
(4 results)
Research Products
(26 results)
-
-
-
-
-
[Journal Article] Retreatment efficacy and safety of tocilizumab in patients with rheumatoid arthritis in recurrence (RESTORE) study.2014
Author(s)
Nishimoto N, Amano K, Hirabayashi Y, Horiuchi T, Ishii T, Iwahashi M, Iwamoto M, Kohsaka H, Kondo M, Matsubara T, Mimura T, Miyahara H, Ohta S, Saeki Y, Saito K, Sano H, Takasugi K, Takeuchi T, Tohma S, Tsuru T, Ueki Y, Yamana J, Hashimoto J, Matsutani T, Murakami M, Takagi N.
-
Journal Title
Mod Rheumatol
Volume: 24(1)
Issue: 1
Pages: 26-32
DOI
Related Report
Peer Reviewed
-
[Journal Article] Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement.2013
Author(s)
Schoels MM, van der Heijde D, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, Gomez-Reino JJ, Jones G, Kvien TK, Murakami M, Nishimoto N, Smolen JS.
-
Journal Title
Ann Rheum Dis
Volume: 72(4)
Issue: 4
Pages: 583-589
DOI
Related Report
Peer Reviewed
-
[Journal Article] Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions2013
Author(s)
Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, Gomez-Reino JJ, Jones G, Kvien TK, Murakami M, 他21名
-
Journal Title
Ann Rheum Dis
Volume: 72(4)
Issue: 4
Pages: 482-492
DOI
Related Report
Peer Reviewed
-
[Journal Article] Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study.2013
Author(s)
Nishimoto N, Amano K, Hirabayashi Y, Horiuchi T, Ishii T, Iwahashi M, Iwamoto M, Kohsaka H, Kondo M, Matsubara T, Mimura T, Miyahara H, Ohta S, Saeki Y, Saito K, Sano H, Takasugi K, Takeuchi T, Tohma S, Tsuru T, Ueki Y, Yamana J, Hashimoto J, Matsutani T, Murakami M, Takagi N.
-
Journal Title
Mod Rheumatol
Volume: 24(1)
Issue: 1
Pages: 17-25
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
[Presentation] T CELL CD80/CD86 CO-STIMULATORY BLOCKADE EFFECTIVELY SUPPRESSES CD25 (+) IN CD4 (+) T CELL SUBPOPULATION BUT NOT THE ACPA TITERS IN THE COURSE OF 48-WEEK TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS2014
Author(s)
Miho Murakami, Mari Ito, Masahiro Sekiguchi, Kiyoshi Matsui, Masayasu Kitano, Yoshitaka Imura, Koichiro Ohmura, 4Takao Fujii, Takanori Kuroiwa, Keiji Maeda, Satoshi Morita, Yutaka Kawahito, Tsuneyo Mimori, Hajime Sano, Norihiro Nishimoto
Organizer
EULAR2014
Place of Presentation
Paris, France
Year and Date
2014-06-11 – 2014-06-14
Related Report
-
[Presentation] T CELL CD80/CD86 CO-STIMULATORY BLOCKADE DOES NOT SUPPRESS CD8 (+) SUBPOPULATION IN THE COURSE OF 48-WEEK TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS2014
Author(s)
Miho Murakami, Mari Ito, Masahiro Sekiguchi, Kiyoshi Matsui, Masayasu Kitano, Yoshitaka Imura, Koichiro Ohmura, 4Takao Fujii, Takanori Kuroiwa, Keiji Maeda, Satoshi Morita, Yutaka Kawahito, Tsuneyo Mimori, Hajime Sano, Norihiro Nishimoto
Organizer
EULAR2014
Place of Presentation
Paris, France
Year and Date
2014-06-11 – 2014-06-14
Related Report
-
-
-
-
-
[Presentation] Comparison Of Pathological Features Of The Lung Lesions Of Systemic IgG4-Related Disease And Multicentric Castleman's Disease2013
Author(s)
Y. Terasaki, S. Ikushima, Y. Ichimura, M. Ujita, Y. Matsuzawa, M. Arita, K. Tomii, Y. Komase, I. Ohwan, T. Kawamura, S. Izumi, M. Murakami, H. Ishimoto, H. Kimura, M. Bando, N. Hada, N. Nishimoto, S. Matsui, T. Ogura.
Organizer
American Thoracic Society 2013
Place of Presentation
Philadelphia
Related Report
-
[Presentation] Abatacept treatment suppresses T CELL activation in anti-cyclic citrullinated peptide antibody (ACPA) positive RA patients but not in acpa negative RA patients.2013
Author(s)
T. Matsutani, M. Murakami, M. Sekiguchi, K. Matsui, M. Kitano, M. Namiki, K. Ohmura, Y. Imura, T. Fujii , T.Kuroiwa, H. Nakahara, S. Hika, K. Maeda, Y. Nozaki, M. Funauchi, K. Murakami, T. Ikawa, S. Irimajiri, A. Nampei, T. Azuma, T. Sasaki, A. Yokota, S. Morita, Y. Kawahito, T. Mimori, H. Sano, N. Nishimoto．
Organizer
EULAR 2013
Place of Presentation
Madrid. Spain
Related Report
-
[Presentation] Changes in cytokine profiles in rheumatoid arthritis patients during abatacept treatment.2013
Author(s)
M. Murakami, T. Matsutani, M. Sekiguchi, K. Matsui, M. Kitano, M. Namiki, K. Ohmura, Y. Imura, T. Fujii, T. Kuroiwa, H. Nakahara, S. Higa, K. Maeda, Y. Nozaki, M. Funauchi, K. Murakami, T. Ikawa, S. Irimajiri, A. Nampei, T. Azuma, T. Sasaki, A. Yokota, S. Morita, Y. Kawahito, T. Mimori, H. Sano, N. Nishimoto.
Organizer
EULAR 2013
Place of Presentation
Madrid. Spain
Related Report
-
-
-
-
