The discovery of the second case of human heme oxygenase-1 deficiency: biological evidence of HO-1 enzyme

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591531
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanazawa University
• Principal Investigator: KOIZUMI SHOICHI 金沢大学, その他部局等, 名誉教授 (50019973)
• Co-Investigator(Renkei-kenkyūsha): YACHIE Akihiro 金沢大学, 医学系, 教授 (40210281) ; WADA Taizou 金沢大学, 医学系, 講師 (30313646) ; NISHIMURA Ryousei 金沢大学, 医学系, 講師 (50324116) ; SUGIMOTO Naotoshi 金沢大学, 医学系, 准教授 (80272954) ; OHTA Kunio 金沢大学, 医学系, 准教授 (00303280) ; NIIDA Yo 金沢大学, 金沢医科大学, 准教授 (40293344) ; SHIMIZU Masaki 金沢大学, 医学系, 講師 (10401902)
• Project Period (FY): 2011 – 2013
• Keywords: ヘムオキシゲナーゼ / ヘムオキシゲナーゼ１欠損症 / 炎症 / 血管炎 / 腎尿細管 / 溶血性貧血 / 血管内皮細胞 / ビリルビン代謝

Research Abstract

Heme oxygenase-1(HO-1) is the rate-limiting enzyme to metabolyze heme, showing antioxidant effects. In 1999, we reported the first case of human HO-1 deficiency. After the 2nd case was discovered in 2011, the 3 subsequent cases have been reported so far. All 5 patients with HO-1 deficiency were characterized by recalcitrant systemic inflammation, asplenia, microangiopathy and hypertention. Clinical data show hemolytic anemia with low serum bilirubin, thrombocytosis and evidences of renal tissue injury. From these data we would like to introduce HO-1 deficiency as a novel autoinflammatory disease.

Research Products

• [Journal Article] Expansion of a liver-infiltrating cytotoxic T-lymphocyte clone in concert with the development of hepatitis-associated aplastic anemia (2013)
  • Author(s): Ikawa, Y., Nishimura, R., Kuroda, R., Mase, S., Araki R., Maeba, H., Wada, T., Toma, T., Koizumi, S., Yachie, A.
  • Journal Title: Brit J Haematol Volume: 161(4) Pages: 599-602
  • Peer Reviewed
• [Journal Article] An infant with recurrent convulsive seizures of 3 weeks duration : Questions (2013)
  • Author(s): Shimizu, M., Niida, Y., Koizumi, S., Yachie, A.
  • Journal Title: Pediatr Nephrol published online
  • DOI: 10.1007/s00467-013-2615-4
  • Peer Reviewed
• [Journal Article] Upregulation of aquaporin expression in the salivary glands of heat-acclimated rats (2013)
  • Author(s): Sugimoto, N., Matsuzaki, K., Ishibashi, H., Tanaka, M., Sawaki, T., Fujita, Y., Kawanami, T., Masaki, Y., Okazaki, T., Sekine, J., Koizumi, S., Yachie, A., Shido, O.
  • Journal Title: Scientific Reports Volume: 3 Pages: 1763
  • Peer Reviewed
• [Journal Article] Compensated inflammation in systemic juvenile idiopathic arthritis : role of alternatively activated macrophages (2012)
  • Author(s): Shimizu M., Yachie, A.
  • Journal Title: Cytokine Volume: 60(1) Pages: 226-232
  • Peer Reviewed
• [Journal Article] Human Heme oxygenase (HO)-1 deficiency presenting with hemolysis, nephritisand asplenia (2011)
  • Author(s): Radhakrishnan,N., Yadav,S.P., Sachdeva,A., Pruthi,P.K., Sawhney,S., Piplani,T., Wada,T., Yachie,A.
  • Journal Title: J Pediatr Hematol Oncol Volume: 33(1) Pages: 74-78
  • Peer Reviewed
• [Journal Article] Urinary heme oxygenase-1 as a sensitive indicator of tubulointerstitial inflammatory damage in various renal diseases (2011)
  • Author(s): Yokoyama, T., Shimizu, M., Ohta, K., Yuno, T., Okajima, M., Wada, T., Toma, T., Koizumi, S., Yachie, A.
  • Journal Title: Am J Nephrol Volume: 33 Pages: 414-420
  • Peer Reviewed
• [Journal Article] Long-term follow-up of a case of hypomagnesemia with secondary hypocalcemia caused by novel TRPM6 mutation
  • Author(s): Shimizu, M., Niida, Y., Koizumi, S., Yachie, A.
  • Journal Title: Pediatric Nephrology Volume: (in press)
  • Peer Reviewed
• [Presentation] Protective role of host mast cells against acute graft-versus-host disease (2013)
  • Author(s): Araki,R., Nishimura, R., Maeba, H., Kuroda, R., Fujii, T., Mase, S., Koizumi, S., Yachie, A.
  • Organizer: 55th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans (USA)
  • Year and Date: 20131207-10
• [Presentation] IFN-gamma-mediated elimination of host DCs by cytokine induced killer cells leads to less GVHD (2013)
  • Author(s): Mase,S., Nishimura, R., Kuroda, R., Fujii,T., Araki, R., Maeba, H., Koizumi, S., Yachie, A.
  • Organizer: 55th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans (USA)
  • Year and Date: 20131207-10
• [Presentation] Monitoring of CD4+ T-cell receptor repertoire helps manage the patients with prolonged GVHD (2013)
  • Author(s): Kuroda, R., Nishimura, R., Mase, S., Fujii, T., Araki, R., Maeba, H., Koizumi, S., Yachie, A.
  • Organizer: 55th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans Convention Center (USA)
  • Year and Date: 20131207-10
• [Presentation] Heme oxygenase-1 deficiency : a novel autoinflammatory disease, associated with systemic inflammation, accelerated tissue injury and endothelial dysfunction (2012)
  • Author(s): Yachie, A., Yokoyama, T., Shimizu, M., Ohta, K., Toma, T., Wada, T., Radhakrishnan, N., Sachdeva, A., Yadav, S.P.
  • Organizer: 15th Biennial Meeting of the European Society of Immunodeficiencies (ESID 2012)
  • Place of Presentation: Florence Convention Center (Italy)
  • Year and Date: 20121003-06
• [Presentation] Allogeneic cytokine-induced killer cells kill dendritic cells efficiently resulting in less graft-versus-host disease (2012)
  • Author(s): Mase,S., Kuroda,R., Maeba,H., Araki,R., Fujiki,T., Koizumi,S., Yachie,A., Nishimura,R.
  • Organizer: 38th Annual meeting of the European group for blood and marrow transplantation (EBMT)
  • Place of Presentation: Geneva Convention Center (Switzerland)
  • Year and Date: 20120401-04
• [Presentation] A genetic variation in the heme oxygenase-1 gene predicts the outcome of HLA-fully-matched unrelated bone marrow transplantation (2011)
  • Author(s): Morishita,E., Maruyama,K., Takami,A., Onizuka,M., Kawase,T., Morishima,Y., Fukuda,T., Kodera,Y., Ohtake,S., Yachie,A., Nakao,S.
  • Organizer: 53rd Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego Convention Center (USA)
  • Year and Date: 20111209-11
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~med2