Contributions
Abstract: P1755
Type: Poster Sessions
Abstract Category: N/A
Neuromyelitis optica (NMO) is a disabling autoimmune neurological disease that is often resistant to therapy. Recent studies have suggested that IL-6 plays a pivotal role in the pathogenesis of NMO, and the potential efficacy of the anti-IL-6 receptor antibody tocilizumab (TCZ) in NMO. However, the mechanism underlying the beneficial effects of TCZ against NMO remains unclear.
A monthely intravenous dose of 8 mg/kg of TCZ was given as an add-on therapy in 19 anti-AQP4-IgG-positive person with NMO/NMO spectrum disorders who were resistant to canonical interventions. Peripheral blood was collected prior to each infusion, and peripheral lymphocyte subsets and gene expression profiles of whole blood were studied.
Despite intensive therapy, the enrolled participants had experienced relapses of NMO before TCZ induction. Alterations of multiple lymphocyte subsets were evident in their peripheral blood at the baseline. After initiating TCZ therapy, the annual relapse rate reduced markedly, and counts of lymphocyte subsets with regulatory function (transitional B cells, CD56high natural killer cells, CD45RA-FoxP3high regulatory T (Treg) cells) increased. Furthermore, we confirmed the functional recovery of CD45RA-CD25high Treg cells. Although neutrophil granule-related genes, especially those related to azurophil granules, were significantly upregulated upon entry, we observed significant reduction in the expression of these genes after one year of TCZ treatment.
The efficacy of TCZ in clinical improvement of NMO was confirmed in the 19 enrolled participants, who were resistant to steroids and immunosuppressive drugs. The beneficial effects of TCZ may be achieved by recovering regulatory lymphocyte subsets and suppressing neutrophil functions by blocking IL-6R signaling.
Disclosure: Dr. T. Matsuoka: nothing to disclosure.
Dr. M. Araki received speaker honoria from Bayer Holding and Takeda Pharmaceutical.
Ms. H. Yamaguchi: nothing to disclosure.
Dr. W. Sato: nothing to disclosure.
Dr. K. Miyamoto: nothing to disclosure.
Dr. S. Kusunoki reports grants from Ministry of Education, Culture, Sports, and Technology of Japan, Agency for Medical Research and Development (AMED) of Japan. He received research grant and speech honorarium from Nihon Pharmaceutical, Teijin, and Japan Blood Products Organization.
Dr. R.Gold received speaker's and board honoraria from Baxter, Bayer Schering, Biogen Idec, CLB Behring, Genzyme, Merck Serono, Novartis, Roche, Stendhal, Talecris, and TEVA. His department received grant support from Bayer Schering, BiogenIdec, Genzyme, Merck Serono, Novartis, and TEVA. He possesses stock options from Merck Serono and Roche.
Dr. T. Yamamura reports grants from Agency for Medical Research and Development (AMED) of Japan and Health and Labor Sciences Research Grant. He received speech honorarium from Bayer Yakuhin, Biogen Japan, CHUGAI PHARMACEUTICAL, DAIICHI SANKYO, Japan Blood Products Organization, Kissei Pharmaceutical, MedPeer, Mitsubishi Tanabe Pharma, Novartis Pharma, OFFICE R&M, Otsuka Pharmaceutical, Sanofi, Sumitomo Dainippon Pharma, and Takeda Pharmaceutical, and research grant from Biogen Japan, Chiome Bioscience, CHUGAI PHARMACEUTICAL, Miraca Research Institute, Novartis Pharma, and Teva Pharmaceutical.
This study was supported by grants from Agency for Medical Research and Development (AMED) of Japan, and Health and Labor Sciences Research Grant.
Abstract: P1755
Type: Poster Sessions
Abstract Category: N/A
Neuromyelitis optica (NMO) is a disabling autoimmune neurological disease that is often resistant to therapy. Recent studies have suggested that IL-6 plays a pivotal role in the pathogenesis of NMO, and the potential efficacy of the anti-IL-6 receptor antibody tocilizumab (TCZ) in NMO. However, the mechanism underlying the beneficial effects of TCZ against NMO remains unclear.
A monthely intravenous dose of 8 mg/kg of TCZ was given as an add-on therapy in 19 anti-AQP4-IgG-positive person with NMO/NMO spectrum disorders who were resistant to canonical interventions. Peripheral blood was collected prior to each infusion, and peripheral lymphocyte subsets and gene expression profiles of whole blood were studied.
Despite intensive therapy, the enrolled participants had experienced relapses of NMO before TCZ induction. Alterations of multiple lymphocyte subsets were evident in their peripheral blood at the baseline. After initiating TCZ therapy, the annual relapse rate reduced markedly, and counts of lymphocyte subsets with regulatory function (transitional B cells, CD56high natural killer cells, CD45RA-FoxP3high regulatory T (Treg) cells) increased. Furthermore, we confirmed the functional recovery of CD45RA-CD25high Treg cells. Although neutrophil granule-related genes, especially those related to azurophil granules, were significantly upregulated upon entry, we observed significant reduction in the expression of these genes after one year of TCZ treatment.
The efficacy of TCZ in clinical improvement of NMO was confirmed in the 19 enrolled participants, who were resistant to steroids and immunosuppressive drugs. The beneficial effects of TCZ may be achieved by recovering regulatory lymphocyte subsets and suppressing neutrophil functions by blocking IL-6R signaling.
Disclosure: Dr. T. Matsuoka: nothing to disclosure.
Dr. M. Araki received speaker honoria from Bayer Holding and Takeda Pharmaceutical.
Ms. H. Yamaguchi: nothing to disclosure.
Dr. W. Sato: nothing to disclosure.
Dr. K. Miyamoto: nothing to disclosure.
Dr. S. Kusunoki reports grants from Ministry of Education, Culture, Sports, and Technology of Japan, Agency for Medical Research and Development (AMED) of Japan. He received research grant and speech honorarium from Nihon Pharmaceutical, Teijin, and Japan Blood Products Organization.
Dr. R.Gold received speaker's and board honoraria from Baxter, Bayer Schering, Biogen Idec, CLB Behring, Genzyme, Merck Serono, Novartis, Roche, Stendhal, Talecris, and TEVA. His department received grant support from Bayer Schering, BiogenIdec, Genzyme, Merck Serono, Novartis, and TEVA. He possesses stock options from Merck Serono and Roche.
Dr. T. Yamamura reports grants from Agency for Medical Research and Development (AMED) of Japan and Health and Labor Sciences Research Grant. He received speech honorarium from Bayer Yakuhin, Biogen Japan, CHUGAI PHARMACEUTICAL, DAIICHI SANKYO, Japan Blood Products Organization, Kissei Pharmaceutical, MedPeer, Mitsubishi Tanabe Pharma, Novartis Pharma, OFFICE R&M, Otsuka Pharmaceutical, Sanofi, Sumitomo Dainippon Pharma, and Takeda Pharmaceutical, and research grant from Biogen Japan, Chiome Bioscience, CHUGAI PHARMACEUTICAL, Miraca Research Institute, Novartis Pharma, and Teva Pharmaceutical.
This study was supported by grants from Agency for Medical Research and Development (AMED) of Japan, and Health and Labor Sciences Research Grant.