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Euntaek Han - One of the best experts on this subject based on the ideXlab platform.
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naturally acquired cellular immune response against plasmodium vivax merozoite surface Protein 1 paralog antigen
Malaria Journal, 2015Co-Authors: Siriruk Changrob, Chae Seung Lim, Takafumi Tsuboi, Chaniya Leepiyasakulchai, Yang Cheng, Patchanee Chootong, Euntaek HanAbstract:Background Plasmodium vivax merozoite surface Protein-1 paralog (PvMSP1P) is a Glycosylphosphatidylinositol-Anchored Protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection.
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naturally acquired cellular immune response against plasmodium vivax merozoite surface Protein 1 paralog antigen
Malaria Journal, 2015Co-Authors: Siriruk Changrob, Chae Seung Lim, Takafumi Tsuboi, Chaniya Leepiyasakulchai, Yang Cheng, Patchanee Chootong, Euntaek HanAbstract:Plasmodium vivax merozoite surface Protein-1 paralog (PvMSP1P) is a Glycosylphosphatidylinositol-Anchored Protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection. Peripheral blood mononuclear cells (PBMCs) from acute and recovery P. vivax infection were obtained for lymphocyte proliferation assay upon PvMSP1P-19 and PvDBP region II antigen stimulation. The culture supernatant was examined for the presence of the cytokines IL-2, TNF, IFN-γ and IL-10 by enzyme-linked immunosorbent assay (ELISA). To determine whether Th1 or Th2 have a memory response against PvMSP1P-19 and PvDBPII Protein antigen, PBMCs from subjects who had recovered from P. vivax infection 8–10 weeks prior to the study were obtained for lymphocyte proliferation assay. Cytokine-producing cells were analysed by flow cytometry. IL-2 was detected at high levels in lymphocyte cultures from acutely infected P. vivax patients upon PvMSP1P-19 stimulation. Analysis of the Th1 or Th2 memory response in PBMC cultures from subjects who had recovered from P. vivax infection showed significantly elevated levels of PvMSP1P-19 and PvDBPII-specific IFN-γ-producing cells (P < 0.05). Interestingly, the response of IFN-γ-producing cells in PvMSP1P stimulation was fourfold greater in recovered subjects than that in acute-infection patients. CD4+ T cells were the major cell phenotype involved in the response to PvMSP1P-19 and PvDBPII antigen. PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure. Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.
Shinji Nakao - One of the best experts on this subject based on the ideXlab platform.
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increased Glycosylphosphatidylinositol Anchored Protein deficient granulocytes define a benign subset of bone marrow failures in patients with trisomy 8
European Journal of Haematology, 2015Co-Authors: Kohei Hosokawa, Takamasa Katagiri, Naomi Sugimori, Yumi Sasaki, Chizuru Saito, Yu Seiki, Kanako Mochizuki, Hirohito Yamazaki, Akiyoshi Takami, Shinji NakaoAbstract:Trisomy 8 (+8), one of the most common chromosomal abnormalities found in patients with myelodysplastic syndromes (MDS), is occasionally seen in patients with otherwise typical aplastic anemia (AA). Although some studies have indicated that the presence of +8 is associated with the immune pathophysiology of bone marrow (BM) failure, its pathophysiology may be heterogeneous. We studied 53 patients (22 with AA and 31 with low-risk MDS) with +8 for the presence of increased Glycosylphosphatidylinositol-Anchored Protein-deficient (GPI-AP(-) ) cells, their response to immunosuppressive therapy (IST), and their prognosis. A significant increase in the percentage of GPI-AP(-) cells was found in 14 (26%) of the 53 patients. Of the 26 patients who received IST, including nine with increased GPI-AP(-) cells and 17 without increased GPI-AP(-) cells, 14 (88% with increased GPI-AP(-) cells and 41% without increased GPI-AP(-) cells) improved. The overall and event-free survival rates of the +8 patients with and without increased GPI-AP(-) cells at 5 yr were 100% and 100% and 59% and 57%, respectively. Examining the peripheral blood for the presence of increased GPI-AP(-) cells may thus be helpful for choosing the optimal treatment for +8 patients with AA or low-risk MDS.
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increased plasma thrombopoietin levels in patients with myelodysplastic syndrome a reliable marker for a benign subset of bone marrow failure
Haematologica, 2013Co-Authors: Yu Seiki, Kohei Hosokawa, Naomi Sugimori, Yumi Sasaki, Chizuru Saito, Hirohito Yamazaki, Akiyoshi Takami, Shinji NakaoAbstract:Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 × 109/L) to determine any correlation to markers associated with immune pathophysiology and outcome. Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels of 320 pg/mL and over had increased Glycosylphosphatidylinositol-Anchored Protein-deficient blood cells (49.1% vs. 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% vs. 65.5%), a higher response rate to immunosuppressive therapy (84.2% vs. 14.3%), and a better 5-year progression-free survival rate (94.1% vs. 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% vs. 44.4% for refractory cytopenia with multilineage dysplasia). In conclusion, increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could, therefore, represent a reliable marker for a benign subset of myelodysplastic syndrome.
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thymoglobuline is as effective as lymphoglobuline in japanese patients with aplastic anemia possessing increased Glycosylphosphatidylinositol Anchored Protein gpi ap deficient cells
Blood, 2011Co-Authors: Hirohito Yamazaki, Kohei Hosokawa, Naomi Sugimori, Chizuru Saito, Kanako Mochizuki, Yu Kiyu, Hiroyuki Takamatsu, Shinji NakaoAbstract:Abstract 1339 Background: Thymoglobuline (TG), a rabbit anti-thymocyte globulin (ATG) preparation which has more potent immunosuppressive effects than horse ATG Lymphoglobuline (LG), has been shown to be as effective as LG as both first and second line immunosuppressive therapy (IST) for aplastic anemia (AA) by several retrospective studies. However, recent prospective studies from the U.S. and Europe have shown a lower effectiveness of TG compared to horse anti-thymocyte globulin (ATG). The conflicting results may be due to the heterogeneity in the pathophysiology of AA or in the ethnic backgrounds of the patients evaluated. Small populations of Glycosylphosphatidylinositol-Anchored Protein (GPI-AP)-deficient (GPI-AP−) blood cells are detectable in approximately 60% of patients with newly-diagnosed AA, and are associated with a good response to LG (Blood, 107: 1308, 2006). TG may have comparable effects on LG if the study subjects are limited to AA patients possessing GPI-AP− blood cells. Objectives/Methods: To evaluate the effectiveness of TG in Japanese patients with AA, we retrospectively analyzed the outcomes of TG therapy in 57 patients (25 males and 32 females) with AA (40 with severe AA and 17 with non-severe AA) aged from 17 to 84 (median 58) years. Peripheral blood obtained before therapy was examined for the presence of GPI-AP− cells using flow cytometry with liquid fluorescent aerolysin, which can accurately determine the percentage of GPI-AP− granulocytes, erythrocytes, and monocytes at percentages of less than 0.01%. The cut-off values were defined as >0.003% for granulocytes, >0.005% for erythrocytes, and >0.01% for monocytes based on the analytical results of 57 healthy individuals. Results: The cumulative rate of response after 6 months of TG therapy was 59%. Significant increases in the GPI-AP− cell percentages in at least one of the three lineages were detected in 38 (67%) of the 57 patients before therapy. The response rate in patients with increased GPI-AP− cells (PNH+ patients, 69%) was significantly higher than that in patients without GPI-AP− cells (PNH− patients, 35%, P=0.016). Seventeen percent of PNH+ patients achieved complete remission (CR) within 1 year, while only 12% of PNH− patients achieved a CR. 97% of PNH+ and 84% of PNH− patients were alive at the median time of 1 year after the therapy. The response rate in PNH+ patients was comparable to that in PNH+ patients treated with LG (70%) in our recent prospective study. Conclusions: TG is therefore considered to be as effective as LG in Japanese adult patients with AA, particularly in PNH+ AA patients where immune pathophysiology is definitely involved. Alternative therapies may thus need to be considered for PNH− patients. Disclosures: No relevant conflicts of interest to declare.
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gpi Anchored Protein deficient t cells in patients with aplastic anemia and low risk myelodysplastic syndrome implications for the immunopathophysiology of bone marrow failure
European Journal of Haematology, 2011Co-Authors: Takamasa Katagiri, Shigeki Ohtake, Shinji NakaoAbstract:Glycosylphosphatidylinositol-Anchored Protein-deficient (GPI-AP−) T cells can be detected in some patients with bone marrow failure (BMF), but the link between these cells and BMF pathophysiology remains to be elucidated. To clarify the significance of GPI-AP− T cells in BMF, peripheral blood from 562 patients was examined for the presence of CD48−CD59−CD3+ cells using high-resolution flow cytometry (FCM), and the GPI-AP− T cells were characterized with regard to their phenotype and sensitivity to inhibitory molecules, including herpesvirus entry mediator (HVEM) and a myelosuppressive cytokine, TGF-β. A multi-lineage FCM analysis detected CD48−CD59−CD3+ T cells in 72 (12.8%) of the patients, together with GPI-AP− myeloid cells. Unexpectedly, 12 patients (10 with aplastic anemia and 2 with myelodysplastic syndrome-refractory anemia, 2.1%), who showed clinical features similar to those of other BMF patients with GPI-AP− myeloid cells, such as a good response to immunosuppressive therapy, displayed 0.01–0.3% GPI-AP− cells exclusively in T cells. The CD48−CD59− T cells consisted of predominantly effector memory (EM) and terminal effector cells, while CD48−CD59− T cells from non-BMF patients who had received anti-CD52 antibody only showed EM and central memory phenotypes. TGF-β and HVEM capable of inhibiting T-cell proliferation via its GPI-AP CD160 ligation suppressed the in vitro proliferation of GPI-AP+ T cells more potently than that of GPI-AP− T cells from the same patients. The presence of GPI-AP− T cells, as well as GPI-AP− myeloid cells, may therefore reflect the immunopathophysiology of BMF in which cytokine-mediated suppression of hematopoietic stem cells via GPI-AP-type receptors takes place.
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origin and fate of blood cells deficient in Glycosylphosphatidylinositol Anchored Protein among patients with bone marrow failure
British Journal of Haematology, 2009Co-Authors: Chiharu Sugimori, Naomi Sugimori, Kanako Mochizuki, Hirohito Yamazaki, Akiyoshi Takami, Ken Ishiyama, Yukio Kondo, Hirokazu Okumura, Shinji NakaoAbstract:Peripheral blood from 489 recently diagnosed patients with aplastic anaemia (AA) and 316 with refractory anaemia (RA) of myelodysplastic syndrome was evaluated to characterize CD55(-)CD59(-) [paroxysmal nocturnal haemoglobinuria (PNH)]-type blood cells associated with bone marrow (BM) failure. PNH-type cells were detected in 57% and 20% of patients with AA and RA, respectively. The percentages of PNH-type granulocytes ranged from 0.003% to 94.2% and the distribution was log-normal with a median of 0.178%. Serial analyses of 75 patients with PNH-type cells over 5 years revealed that the percentage of PNH-type cells constantly increased in 13 (17%), persisted in 44 (59%), disappeared in the remaining 18 (24%) although even in the 'Disappearance' group, PNH-type granulocytes persisted for at least 6 months. A scattergram profile of PNH-type cells unique to each patient persisted regardless of the response to immunosuppressive therapy and only single PIGA mutations were detected in PNH-type granulocytes sorted from four patients. These findings suggest that the PNH-type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self-maintenance properties of the individual PIGA mutants.
Yang Cheng - One of the best experts on this subject based on the ideXlab platform.
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naturally acquired cellular immune response against plasmodium vivax merozoite surface Protein 1 paralog antigen
Malaria Journal, 2015Co-Authors: Siriruk Changrob, Chae Seung Lim, Takafumi Tsuboi, Chaniya Leepiyasakulchai, Yang Cheng, Patchanee Chootong, Euntaek HanAbstract:Background Plasmodium vivax merozoite surface Protein-1 paralog (PvMSP1P) is a Glycosylphosphatidylinositol-Anchored Protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection.
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naturally acquired cellular immune response against plasmodium vivax merozoite surface Protein 1 paralog antigen
Malaria Journal, 2015Co-Authors: Siriruk Changrob, Chae Seung Lim, Takafumi Tsuboi, Chaniya Leepiyasakulchai, Yang Cheng, Patchanee Chootong, Euntaek HanAbstract:Plasmodium vivax merozoite surface Protein-1 paralog (PvMSP1P) is a Glycosylphosphatidylinositol-Anchored Protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection. Peripheral blood mononuclear cells (PBMCs) from acute and recovery P. vivax infection were obtained for lymphocyte proliferation assay upon PvMSP1P-19 and PvDBP region II antigen stimulation. The culture supernatant was examined for the presence of the cytokines IL-2, TNF, IFN-γ and IL-10 by enzyme-linked immunosorbent assay (ELISA). To determine whether Th1 or Th2 have a memory response against PvMSP1P-19 and PvDBPII Protein antigen, PBMCs from subjects who had recovered from P. vivax infection 8–10 weeks prior to the study were obtained for lymphocyte proliferation assay. Cytokine-producing cells were analysed by flow cytometry. IL-2 was detected at high levels in lymphocyte cultures from acutely infected P. vivax patients upon PvMSP1P-19 stimulation. Analysis of the Th1 or Th2 memory response in PBMC cultures from subjects who had recovered from P. vivax infection showed significantly elevated levels of PvMSP1P-19 and PvDBPII-specific IFN-γ-producing cells (P < 0.05). Interestingly, the response of IFN-γ-producing cells in PvMSP1P stimulation was fourfold greater in recovered subjects than that in acute-infection patients. CD4+ T cells were the major cell phenotype involved in the response to PvMSP1P-19 and PvDBPII antigen. PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure. Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.
D Westaway - One of the best experts on this subject based on the ideXlab platform.
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doppel is an n glycosylated Glycosylphosphatidylinositol Anchored Protein expression in testis and ectopic production in the brains ofprnp 0 0 mice predisposed to purkinje cell loss
Journal of Biological Chemistry, 2000Co-Authors: Gregory L Silverman, Stanley B Prusiner, Richard C Moore, Peter Mastrangelo, Ying Yang, Patrick Tremblay, Fred E Cohen, D WestawayAbstract:Abstract The Prnd gene encodes a homolog of the cellular prion Protein (PrPC) called doppel (Dpl). Up-regulation of Prnd mRNA in two distinct lines of PrP gene ablated (Prnp 0/0) mice, designatedRcm0 and Ngsk, is associated with death of Purkinje cells. Using recombinant Dpl expressed in Escherichia coli and mouse neuroblastoma cells we demonstrate that wild type (wt) Dpl, like PrPC, adopts a predominantly α-helical conformation, forms intramolecular disulfide bonds, has twoN-linked oligosaccharides, and is presented on the cell surface via a Glycosylphosphatidylinositol anchor. Dpl Protein was detected in testis of wt mice. Using Triton X-114 phase partitioning to enrich for Glycosylphosphatidylinositol-Anchored Proteins, Dpl was detected in brain samples from Rcm0 Prnp 0/0mice but was absent in equivalent samples from wt mice and ZrchI Prnp 0/0 mice, indicating that ectopic expression of this Protein may cause cerebellar pathology in Rcm0 mice. Biochemical and structural similarities between PrPC and Dpl documented here parallel the observation that ataxic Ngsk Prnp 0/0 mice can be rescued by overexpression of wild-type PrP transgenes, and suggest that cell surface PrPC can antagonize the toxic effect of Dpl expressed in the central nervous system.
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doppel is an n glycosylated Glycosylphosphatidylinositol Anchored Protein expression in testis and ectopic production in the brains ofprnp 0 0 mice predisposed to purkinje cell loss
Journal of Biological Chemistry, 2000Co-Authors: Gregory L Silverman, Stanley B Prusiner, Richard C Moore, Peter Mastrangelo, Ying Yang, Patrick Tremblay, Kefeng Qin, Frederick Cohen, D WestawayAbstract:The Prnd gene encodes a homolog of the cellular prion Protein (PrPC) called doppel (Dpl). Up-regulation of Prnd mRNA in two distinct lines of PrP gene ablated (Prnp 0/0) mice, designatedRcm0 and Ngsk, is associated with death of Purkinje cells. Using recombinant Dpl expressed in Escherichia coli and mouse neuroblastoma cells we demonstrate that wild type (wt) Dpl, like PrPC, adopts a predominantly α-helical conformation, forms intramolecular disulfide bonds, has twoN-linked oligosaccharides, and is presented on the cell surface via a Glycosylphosphatidylinositol anchor. Dpl Protein was detected in testis of wt mice. Using Triton X-114 phase partitioning to enrich for Glycosylphosphatidylinositol-Anchored Proteins, Dpl was detected in brain samples from Rcm0 Prnp 0/0mice but was absent in equivalent samples from wt mice and ZrchI Prnp 0/0 mice, indicating that ectopic expression of this Protein may cause cerebellar pathology in Rcm0 mice. Biochemical and structural similarities between PrPC and Dpl documented here parallel the observation that ataxic Ngsk Prnp 0/0 mice can be rescued by overexpression of wild-type PrP transgenes, and suggest that cell surface PrPC can antagonize the toxic effect of Dpl expressed in the central nervous system.
Siriruk Changrob - One of the best experts on this subject based on the ideXlab platform.
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naturally acquired cellular immune response against plasmodium vivax merozoite surface Protein 1 paralog antigen
Malaria Journal, 2015Co-Authors: Siriruk Changrob, Chae Seung Lim, Takafumi Tsuboi, Chaniya Leepiyasakulchai, Yang Cheng, Patchanee Chootong, Euntaek HanAbstract:Background Plasmodium vivax merozoite surface Protein-1 paralog (PvMSP1P) is a Glycosylphosphatidylinositol-Anchored Protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection.
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naturally acquired cellular immune response against plasmodium vivax merozoite surface Protein 1 paralog antigen
Malaria Journal, 2015Co-Authors: Siriruk Changrob, Chae Seung Lim, Takafumi Tsuboi, Chaniya Leepiyasakulchai, Yang Cheng, Patchanee Chootong, Euntaek HanAbstract:Plasmodium vivax merozoite surface Protein-1 paralog (PvMSP1P) is a Glycosylphosphatidylinositol-Anchored Protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection. Peripheral blood mononuclear cells (PBMCs) from acute and recovery P. vivax infection were obtained for lymphocyte proliferation assay upon PvMSP1P-19 and PvDBP region II antigen stimulation. The culture supernatant was examined for the presence of the cytokines IL-2, TNF, IFN-γ and IL-10 by enzyme-linked immunosorbent assay (ELISA). To determine whether Th1 or Th2 have a memory response against PvMSP1P-19 and PvDBPII Protein antigen, PBMCs from subjects who had recovered from P. vivax infection 8–10 weeks prior to the study were obtained for lymphocyte proliferation assay. Cytokine-producing cells were analysed by flow cytometry. IL-2 was detected at high levels in lymphocyte cultures from acutely infected P. vivax patients upon PvMSP1P-19 stimulation. Analysis of the Th1 or Th2 memory response in PBMC cultures from subjects who had recovered from P. vivax infection showed significantly elevated levels of PvMSP1P-19 and PvDBPII-specific IFN-γ-producing cells (P < 0.05). Interestingly, the response of IFN-γ-producing cells in PvMSP1P stimulation was fourfold greater in recovered subjects than that in acute-infection patients. CD4+ T cells were the major cell phenotype involved in the response to PvMSP1P-19 and PvDBPII antigen. PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure. Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.