Kyushu University Academic Staff Educational and Research Activities Database
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Masataka Ishimura Last modified date:2022.06.15

Lecturer / Department of Pediatrics
Faculty of Medical Sciences

Graduate School

 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Country of degree conferring institution (Overseas)
Field of Specialization
Pediatric Hematology, Immunology
ORCID(Open Researcher and Contributor ID)
Total Priod of education and research career in the foreign country
Research Interests
  • Primary immunodeficiency diseases
    keyword : PID, epidemiology
  • Pathogeneisis of autoinflammatory disorder
    keyword : autoinflammatory disorder, pediodic fever
  • regenerative medicine for congenital coagulation defect
    keyword : regenerative medicine
  • Research of Early diagnostic method for HNL and JIA
    keyword : early diagnosis method
  • Gene therapy
    keyword : gene therapy
Academic Activities
1. Masataka Ishimura, Hiroyuki Yamamoto, Yumi Mizuno, Hidetoshi Takada, Motohiro Goto, Takehiko Doi, Takayuki Hoshina, Shouichi Ohga, Koichi Ohshima, Toshiro Hara, A non-invasive diagnosis of histiocytic necrotizing lymphadenitis by means of gene expression profile analysis of peripheral blood mononuclear cells., Journal of clinical immunology, 10.1007/s10875-013-9897-y, 33, 5, 1018-26, 2013.07, Histiocytic necrotizing lymphadenitis (HNL), also called Kikuchi-Fujimoto disease, is a benign, self-limiting inflammatory disease with fever and painful cervical lymphadenopathy of unknown etiology. A lymph node biopsy is required for the definitive diagnosis because of no specific symptoms or laboratory findings for HNL. To establish the rapid non-invasive diagnostic method for this disease, we investigated genes specifically expressed in the patients by analyzing whole transcriptome using microarray analysis of peripheral blood mononuclear cells (PBMC). The top five up-regulated genes (IFI44L, CXCL10, GBP1, EPSTI1 and IFI27) in HNL were interferon-induced genes (ISGs). The expression levels of the up-regulated genes by microarray were verified by quantitative PCR. High levels of serum CXCL10 concentration were confirmed at the symptomatic phase of HNL patients. The expression levels of these 5 genes positively correlated with each other (r(2) = 0.28-0.60). The genes were also highly expressed in HNL lymph nodes. The discriminant analysis using the expression levels of these five genes distinguished HNL with 84% accuracy. The combination of up-regulated ISGs in HNL seemed to be a specific response induced by viral infections or autoantigens. An analysis of the gene expression profile of PBMC may provide a rapid non-invasive diagnosis of HNL..
2. Tetsuko Kobayashi, Yuhki Koga, Masataka Ishimura, Kentaro Nakashima, Wakako Kato, Hiroaki Ono, Motoshi Sonoda, Katsuhide Eguchi, Reiji Fukano, Satoshi Honjo, Yoshinao Oda, Shouichi Ohga, Fever and Skin Involvement at Diagnosis Predicting the Intractable Langerhans Cell Histiocytosis: 40 Case-Series in a Single Center., Journal of pediatric hematology/oncology, 10.1097/MPH.0000000000001080, 40, 3, e148-e153, 2018.04, Langerhans cell histiocytosis (LCH) occurs as a clonal disease with enigmatic immune responses. LCH patients occasionally present with fever, although the significance remains elusive. We investigated the predicting factors for developing intractable disease of refractory and/or reactivated LCH. In total, 40 pediatric LCH patients managed in Kyushu University from 1998 to 2014 were enrolled. The medical records were analyzed retrospectively. Sixteen patients suffered from multisystem (MS) LCH involving risk organs (ROs) (n=4) or not (n=12). In total, 24 patients had single-system LCH affecting bone (multi n=8, single n=13), skin (n=2), or lymph node lesions (n=1). Eight patients had the intractable disease of 7 MS or 1 multibone LCH. Two patients died from MS LCH with or without RO involvement. Ten patients showed persistent fever (>38°C) at onset. Intractable cases had fever, RO and skin involvement, leukocytosis, coagulopathy, microcytic anemia, higher levels of soluble interleukin-2 receptor and C-reactive protein, more frequently at diagnosis. Multivariate analysis indicated that fever and skin lesions at diagnosis were independently associated with the intractability (odds ratio: fever, 35.5; 95% confidence interval, 3.0-1229.1; skin lesions, 24.6; 95% confidence interval, 1.9-868.7). Initial fever and skin involvement might predict the development of intractable and fatal-risk LCH even without the RO involvement..
3. Masataka Ishimura, Mitsumasa Saito, Shouichi Ohga, Takayuki Hoshina, Haruhisa Baba, Michiyo Urata, Ryutaro Kira, Hidetoshi Takada, Koichi Kusuhara, Dongchon Kang, Toshiro Hara, Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy., European journal of pediatrics, 10.1007/s00431-008-0816-9, 168, 6, 673-7, 2009.06, A 13-month-old Japanese female with Haemophilus influenzae type b meningitis presented with unusually severe septic shock and cerebral infarction in half a day of fever. The initial therapy of plasma-derived activated protein C (Anact C) led to an impressive effect on the aggressive condition. However, purpura fulminans and the consistent decline of plasma protein C activity (<20%) required prolonged activated protein C therapy and gene analysis. The patient carried a novel heterozygous mutation of PROC (exon 4; 335 GAC>TAC, Asp46Tyr). This is the first report of infectious purpura fulminans in a protein C-deficient heterozygote. The clinical onset and treatment course adequately corroborated the aggravated immune/hemostatic reactions and the cytoprotective effects of activated protein C replacement in human heterozygous protein C deficiency. The monitoring of plasma protein C activity and sufficient administration of activated protein C product could improve the outcome of severe sepsis in children..
4. Masataka Ishimura, Shouichi Ohga, Masako Ichiyama, Koichi Kusuhara, Hidetoshi Takada, Toshiro Hara, Masaharu Takahashi, Hiroaki Okamoto, Hepatitis-associated aplastic anemia during a primary infection of genotype 1a torque teno virus., European journal of pediatrics, 10.1007/s00431-009-1116-8, 169, 7, 899-902, 2010.07, A 12-year-old Japanese boy suffered from severe acute hepatitis and pancytopenia. The patient underwent successful bone marrow transplantation from an HLA-identical sister. Torque teno virus (TTV) DNA of genotype 1a and IgM-class antibody against the virus were detected in sera at the onset of hepatitis. TTV/1a DNA and anti-TTV/1a IgM antibody levels were undetectable on the 16th and 46th days after the onset of illness, respectively. Anti-TTV/1a IgG antibody was positive throughout the observation period. Sequential viral load and anti-TTV/1a IgM antibody suggested a primary infection of TTV/1a. Genomic sequence of the virus coincided with that of the original strain first isolated from human. TTV DNA was quantified at 130 copies in 10(5) bone marrow mononuclear cells, which suggested that infection of hematopoietic cells might be the cause of aplasia. This is the first report of TTV hepatitis-associated aplastic anemia assessed by the anti-TTV antibodies and viral load in peripheral blood and bone marrow..
5. Takashi Imai, Akira Shiraishi, Kei Nishiyama, Masataka Ishimura, Shouichi Ohga, Lipopolysaccharide-induced monocyte death in a novel ZnF7 domain mutation of TNFAIP3., The journal of allergy and clinical immunology. In practice, 10.1016/j.jaip.2020.01.026, 8, 6, 2071-2074, 2020.06.
6. Masataka Ishimura, Shouichi Ohga, Yoshihisa Nagatoshi, Jun Okamura, Tatsuro Tajiri, Kenichi Kohashi, Yoshinao Oda, Hidetoshi Takada, Toshiro Hara, Malignant hepatic tumor occurring 10 yrs after a histocompatible sibling donor bone marrow transplantation for severe aplastic anemia., Pediatric transplantation, 11, 8, 945-9, 2007.12, A 13-yr-old boy developed post-transplant liver tumor. At three yrs of age, this patient underwent a histocompatible sibling donor BMT for severe aplastic anemia, after a conditioning with antithymocyte globulin and cyclophosphamide. He became a HBV carrier after BMT. Stable mixed chimerism and mild thrombocytopenia, but no active hepatitis continued. At age 13, abdominal pain was a sign of massive tumor. Extremely high levels of alpha-fetoprotein indicated the clinical diagnosis of hepatoblastoma that might be the first report as post-BMT malignancy. The necropsy specimens revealed that the tumor was recipient cell-origin and showed the histopathological features of both hepatoblastoma and hepatocellular carcinoma. Prolonged mixed chimerism and hepatitis virus infection might induce a rare oncogenesis after non-irradiated conditioning..
7. Ishimura M, Takada H, Doi T, Imai K, Sasahara Y, Kanegane H, Nishikomori R, Morio T, Heike T, Kobayashi M, Ariga T, Tsuchiya S, Nonoyama S, Miyawaki T, Hara T , Nationwide Survey of Patients with Primary Immunodeficiency Diseases in Japan, Journal of Clinical Immunology, 31, 968-976, 2011.12.
8. Masataka Ishimura, Hidetoshi Takada, Takehiko Doi, Kousuke Imai, Yoji Sasahara, Hirokazu Kanegane, Ryuta Nishikomori, Tomohiro Morio, Toshio Heike, Masao Kobayashi, Tadashi Ariga, Shigeru Tsuchiya, Shigeaki Nonoyama, Toshio Miyawaki, Toshiro Hara, Nationwide survey of patients with primary immunodeficiency diseases in Japan., Journal of clinical immunology, 10.1007/s10875-011-9594-7, 31, 6, 968-76, 2011.12, To determine the prevalence and clinical characteristics of patients with in Japan, we conducted a nationwide survey of primary immunodeficiency disease (PID) patients for the first time in 30 years. Questionnaires were sent to 1,224 pediatric departments and 1,670 internal medicine departments of Japanese hospitals. A total of 1,240 patients were registered. The estimated number of patients with PID was 2,900 with a prevalence of 2.3 per 100,000 people and homogenous regional distribution in Japan. The male-to-female ratio was 2.3:1 with a median age of 12.8 years. Adolescents or adults constituted 42.8% of the patients. A number of 25 (2.7%) and 78 (8.5%) patients developed malignant disorders and immune-related diseases, respectively, as complications of primary immunodeficiency disease. Close monitoring and appropriate management for these complications in addition to prevention of infectious diseases is important for improving the quality of life of PID patients..
9. Motoshi Sonoda, Masataka Ishimura, Katsuhide Eguchi, Akira Shiraishi, Shunsuke Kanno, Noriyuki Kaku, Hirosuke Inoue, Yoshitomo Motomura, Masayuki Ochiai, Yasunari Sakai, Manabu Nakayama, Osamu Ohara, Shouichi Ohga, Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis., International journal of hematology, 10.1007/s12185-019-02738-3, 111, 1, 131-136, 2020.01, Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 109/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH..
10. Motoshi Sonoda, Masataka Ishimura, Katsuhide Eguchi, Yutaro Yada, Nina Lenhartová, Akira Shiraishi, Tamami Tanaka, Yasunari Sakai, Shouichi Ohga, Progressive B cell depletion in human MALT1 deficiency., Clinical and experimental immunology, 10.1111/cei.13662, 206, 3, 237-247, 2021.12, Mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1)-deficiency is a rare combined immunodeficiency characterized by recurrent infections, dermatitis and enteropathy. We herein investigate the immunological profiles of our patient and previously reported children with MALT1-deficiency. A mutation analysis was performed by targeted panel sequencing for primary immunodeficiency. Lymphocyte subset, activation and B cell differentiation were analyzed by flow cytometry and t-distributed stochastic neighbor embedding. Pneumocystis pneumonia developed in a 6-month-old Japanese infant with atopic dermatitis, enteritis and growth restriction. This infant showed agammaglobulinemia without lymphopenia. At 8 years of age, the genetic diagnosis of MALT1-deficiency was confirmed on a novel homozygous mutation of c.1102G>T, p.E368X. T cell stimulation tests showed impairments in the production of interleukin-2, phosphorylation of nuclear factor kappa B (NF-κB) p65 and differentiation of B cells. In combination with the literature data, we found that the number of circulatory B cells, but not T cells, were inversely correlated with the age of patients. The hematopoietic cell transplantation (HCT) successfully reconstituted the differentiation of mature B cells and T cells. These data conceptualize that patients with complete MALT1-deficiency show aberrant differentiation and depletion of B cells. The early diagnosis and HCT lead to a cure of the disease phenotype associated with the loss-of-function mutations in human CARD11..
11. Sayaka Okuzono, Masataka Ishimura, Shunsuke Kanno, Motoshi Sonoda, Noriyuki Kaku, Yoshitomo Motomura, Hisanori Nishio, Utako Oba, Masuo Hanada, Jun-Ichi Fukushi, Michiyo Urata, Dongchon Kang, Hidetoshi Takada, Shouichi Ohga, Streptococcus pyogenes-purpura fulminans as an invasive form of group A streptococcal infection., Annals of clinical microbiology and antimicrobials, 10.1186/s12941-018-0282-9, 17, 1, 31-31, 2018.07, BACKGROUND: Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-purpura fulminans with literature review of the disease. CASE PRESENTATION: A 3-year-old boy showed limping, lethargy and acral gangrene within 24 h. A diagnosis of S. pyogenes-purpura fulminans was made for bacterial isolation from throat and peripheral blood. Intensive therapy led to a survival with amputation of the left distal metatarsal bone, and normal development. The isolated M12 carried no mutation of csrS/R or rgg. Thrombophilia or immunodeficiency was excluded. DISCUSSION: Twelve-reported cases (9 pediatric and 3 elderly) of S. pyogenes-purpura fulminans started with shock and coagulopathy. Five patients age < 8 years had no underlying disease and survived. One youngest and two immunocompromised patients died. CONCLUSION: Streptococcus pyogenes-acute infectious purpura fulminans is a distinctive rare form of aggressive GAS infections..
12. Masataka Ishimura, Shouichi Ohga, Akihiko Nomura, Taikai Toubo, Eiji Morihana, Yusuke Saito, Hisanori Nishio, Makoto Ide, Hidetoshi Takada, Toshiro Hara, Successful umbilical cord blood transplantation for severe chronic active Epstein-Barr virus infection after the double failure of hematopoietic stem cell transplantation., American journal of hematology, 80, 3, 207-12, 2005.11, An 11-year-old boy with severe chronic active Epstein-Barr virus infection (CAEBV) underwent successful cord blood transplantation (CBT) after consecutive failure of peripheral blood and bone marrow transplantation from his HLA-mismatched mother. CB cells from an unrelated donor were infused after conditioning with total body irradiation (12 Gy), melphalan (120 mg/m(2)), and etoposide (600 mg/m(2)). Complete remission without circulating EBV-DNA has continued for 15 months after a delayed hematologic recovery. This is the first successful report of CBT for CAEBV. CB may therefore be an alternate source of stem cells for the curative treatment of CAEBV, despite the absence of EBV-specific cytotoxic T lymphocytes..
13. Hikaru Kanemasa, Masataka Ishimura, Katsuhide Eguchi, Tamami Tanaka, Etsuro Nanishi, Akira Shiraishi, Motohiro Goto, Yoshitomo Motomura, Shouichi Ohga, The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis., Scientific reports, 10.1038/s41598-021-93831-3, 11, 1, 14396-14396, 2021.07, CD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell-cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2..
1. 石村 匡崇, An Early and Non-invasive Diagnostic Method for Histiocytic Necrotizing Lymphadenitis

, The 25th Fukuoka International Symposium on Pediatric/Maternal-child health Research, 2014.08.
Membership in Academic Society
  • Japanese Society for Immunodeficiency and Autoinflammatory diseases
  • Japanese Society for Pediatric Infectious Diseases
  • Japan Pediatric Society
  • Japanese society of hematology
  • The Japanese society of Pediatric hematology/oncology
  • Japanese society for immunology
  • The Japan Society for Clinical Immunology
  • Pediatric Rheumatology association of Japan
  • The Japanese Society on Thrombosis and Hemostasis
Other Educational Activities
  • 2018.11.