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好酸球性消化管疾患研究室

研究室紹介

好酸球性消化管疾患には、新生児-乳児消化管アレルギーと、幼児～成人の好酸球性胃腸炎/食道炎があります。いずれも、主に食物蛋白に対する非IgE依存性反応による炎症が原因と考えられるようになってきました。

西暦2000年前後から、我が国において新生児、乳児において反復嘔吐や血便、体重増加不良が急激に増加し、重症化することもあります。また、幼児～成人の好酸球性胃腸炎も炎症が生涯持続する場合があり問題になっています。これらの疾患概念構築、診断検査開発、治療法開発、原因究明を目的として研究を行っています。


研究内容

  1. 疾患概念構築

    急激に増加したこともあり、疾患概念が定まっていません。疾患の特徴を明らかにし、疾患サブグループを特定するなど、診療に役立つ事実を発見したいと思います。

  2. 診断検査開発

    除外すべき鑑別疾患も多く、診断に難渋することが多いため、免疫アレルギー感染研究部と協同して血液、便、消化管組織を使用した検査法開発を行っています。

  3. 治療法開発

    特に持続型の好酸球性胃腸炎の治療法は整備が遅れています。病院アレルギーセンターにおいて"多種食物除去とその後の原因食物特定治療"を開発中であり、良好な成績を得ています。

  4. 原因究明

    2000年前後から増加したことを考えると、環境因子が主体となっている可能性が高いと思われます。全国調査、疾患コホートによって、発症リスクファクターの同定を企図しています。

  5. 情報の公開

    得られた知識、診断法、治療法を広く公開し、全国の患者さん、ご家族、医療者と共有したいと考えています。


スタッフ

好酸球性消化管疾患研究室

野村 伊知郎（室長）

室員

鈴木 啓子（研究員）
永嶋 早織（研究員）
楠田 理奈（研究員）
石井 美穂（事務補助員）

業績

2022

  1. Nagashima S, Yamamoto M, Inuzuka Y, Irahara M, Miyaji Y, Tadaki H, Ito S, Masuda S, Ito Y, Saito Y, Kobayashi S, Morita H, Yoshioka T, Shimizu H, Arai K, Ohya Y, Saito H, Matsumoto K, Nomura I. Tolerability and safety of a new elimination diet for pediatric eosinophilic gastritis and duodenitis. Allergol Int. 2022, in press.
  2. Nishimura K, Yamamoto-Hanada K, Sato M, Toyokuni K, Ogita H, Kiguchi T, Miyagi Y, Inuzuka Y, Saito-Abe M, Irahara M, Ishikawa F, Kabashima S, Miyaji Y, Fukuie T, Nomura I, Ohya Y. Remission of Acute Food Protein-Induced Enterocolitis Syndrome Confirmed by Oral Food Challenges in Japan. Nutrients. 2022,14:4158.
  3. Dellon ES, Gonsalves N, Abonia JP,, Nomura I,, Rothenberg ME, Furuta GT, Aceves SS. International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature. Clin Gastroenterol Hepatol. 2022:S1542-3565(22)00143-4.

2021

  1. Yamamoto M, Nagashima S, Yamada Y, Murakoshi T, Shimoyama Y, Takahashi S, Seki H, Kobayashi T, Hara Y, Tadaki H, Ishimura N, Ishihara S, Kinoshita Y, Morita H, Ohya Y, Saito H, Matsumoto K, Nomura I. Comparison of Nonesophageal Eosinophilic Gastrointestinal Disorders with Eosinophilic Esophagitis: A Nationwide Survey. J Allergy Clin Immunol Pract. 2021;9:3339-3349.e8.
  2. Miyagi Y, Yamamoto-Hanada K, Ogita H, Kiguchi T, Inuzuka Y, Toyokuni K, Nishimura K, Irahara M, Ishikawa F, Sato M, Saito-Abe M, Miyaji Y, Kabashima S, Fukuie T, Nomura I, Ohya Y. Avoidance of Hen's Egg Based on IgE Levels Should Be Avoided for Children With Hen's Egg Allergy. Front Pediatr. 2021 Jan 15;8:583224.
  3. Suzuki H, Tsutsumi Y, Morita H, Motomura K, Umehara N, Sago H, Ito Y, Arai K, Yoshioka T, Ohya Y, Saito H, Matsumoto K, Nomura I. Cord blood eosinophilia precedes neonatal onset of food-protein-induced enterocolitis syndrome (FPIES). Allergol Int. 2021;70:262-265.

2020

  1. Anna Nowak-Wegrzyn, Antonella Cianferoni, J A Bird, Alessandro Fiocchi, Jean Christoph Caubet, Stefania Arasi, Ashis V Barad, Theresa Bingemann, Terri Brown-Whitehorn, Raquel Durban, Todd Green, George Konstantinou, Stephanie Leonard, Jennifer Lightdale, Antonella Muraro, Ichiro Nomura, Jonathan Spergel, Carina Venter, Managing food protein-induced enterocolitis syndrome during the coronavirus disease 2019 pandemic: Expert recommendations. Ann Allergy Asthma Immunol. 2020;125:14-16.
  2. Complementary and alternative medicine and atopic dermatitis in children. Sato M, Yamamoto-Hanada K, Yang L, Irahara M, Ishikawa F, Iwama-Mitsui M, Saito-Abe M, Miyaji Y, Inagaki S, Fukuie T, Nomura I, Narita M, Suzuki K, Ohya Y.J Dermatol Sci. 2020;97:80-82.
  3. Suzuki H, Tsutsumi Y, Morita H, Motomura K, Umehara N, Sago H, Ito Y, Arai K, Yoshioka T, Ohya Y, Saito H, Matsumoto K, Nomura I. Cord blood eosinophilia precedes neonatal onset of food-protein-induced enterocolitis syndrome (FPIES).Allergol Int. 2021;70:262-265.

2017

  1. Morita H, Suzuki H, Orihara K, Motomura K, Matsuda A, Ohya Y, Saito H, Nomura I, Matsumoto K. Food protein-induced enterocolitis syndromes with and without bloody stool have distinct clinicopathologic features. J Allergy Clin Immunol. 2017 Jun 16.
  2. Ishihara S, Shoda T, Ishimura N, Ohta S, Ono J, Azuma Y, Okimoto E, Izuhara K, Nomura I, Matsumoto K, Kinoshita Y. Serum Biomarkers for the Diagnosis of Eosinophilic Esophagitis and Eosinophilic Gastroenteritis. Intern Med. 2017 Nov 1;56(21):2819-2825.
  3. Mitsui M, Shoda T, Natsume O, Nomura I, Narita M, Fukuda A, Sakamoto S, Kasahara M, Ohya Y. Factors Associated with Development of Food Allergy in Young Children after Liver Transplantation: A Retrospective Analysis of 10 Years' Experience. J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1698-1706.
  4. Sato M, Shoda T, Shimizu H, Orihara K, Futamura K, Matsuda A, Yamada Y, Irie R, Yoshioka T, Shimizu T, Ohya Y, Nomura I, Matsumoto K, Arai K. Gene Expression Patterns in Distinct Endoscopic Findings for Eosinophilic Gastritis in Children. J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1639-1649.e2.
  5. Nowak-Węgrzyn A, Chehade M, Groetch ME, Spergel JM, Wood RA, Allen K, Atkins D, Bahna S, Barad AV, Berin C, Brown Whitehorn T, Burks AW, Caubet JC, Cianferoni A, Conte M, Davis C, Fiocchi A, Grimshaw K, Gupta R, Hofmeister B, Hwang JB, Katz Y, Konstantinou GN, Leonard SA, Lightdale J, McGhee S, Mehr S, Sopo SM, Monti G, Muraro A, Noel SK, Nomura I, Noone S, Sampson HA, Schultz F, Sicherer SH, Thompson CC, Turner PJ, Venter C, Westcott-Chavez AA, Greenhawt M. International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2017 Apr;139(4):1111-1126.e4.
  6. Shoda T, Matsuda A, Nomura I, Okada N, Orihara K, Mikami H, Ishiura N, Ishihara S, Matsumoto K, Kinoshita Y. Eosinophilic esophagitis versus proton pump inhibitor-responsive esophageal eosinophilia: Transcriptome analysis. J Allergy Clin Immunol. 2017 Jun;139(6):2010-2013.e4.

2016

  1. Shoda T, Matsuda A, Arai K, Shimizu H, Morita H, Orihara K, Okada N, Narita M, Ohya Y, Saito H, Matsumoto K, Nomura I. Sera of infantile eosinophilic gastroenteritis patients showed　specific elevation of both thymic stromal lymphopoietin and interleukin-33. J Allergy Clin Immunol. 2016.

2015

  1. Shoda T, Morita H, Nomura I, Ishimura N, Ishihara S, Matsuda A, Matsumoto K, Kinoshita Y. Comparison of gene expression profiles in eosinophilic esophagitis (EoE) between Japan and Western countries. Allergol Int. 2015;64:260-5.
  2. Ito J, Fujiwara T, Kojima R, Nomura I. Racial differences in eosinophilic gastrointestinal disorders among Caucasian and Asian. Allergol Int. 2015;64:253-9.
  3. Horimukai K, Hayashi K, Tsumura Y, Nomura I, Narita M, Ohya Y, Saito H, Matsumoto K. Total serum IgE level influences oral food challenge tests for IgE-mediated food allergies. Allergy. 2015;70:334-7.

2014

  1. Urisu A, Ebisawa M, Ito K, Aihara Y, Ito S, Mayumi M, Kohno Y, Kondo N; Japanese Guideline for Food Allergy 2014. Committee for Japanese Pediatric Guideline for Food Allergy; Japanese Society of Pediatric Allergy and Clinical Immunology; Japanese Society of Allergology. Allergol Int. 2014;63:399-419.

2013

  1. Morita H, Nomura I, Matsuda A, Saito H, Matsumoto K. Gastrointestinal food allergy in infants. Allergol Int. 2013;62:297-307.
  2. Morita H, Nomura I, Orihara K, Yoshida K, Akasawa A, Tachimoto H, Ohtsuka Y, Namai Y, Futamura M, Shoda T, Matsuda A, Kamemura N, Kido H, Takahashi T, Ohya Y, Saito H, Matsumoto K. Antigen-specific T-cell responses in patients with non-IgE-mediated gastrointestinal food allergy are predominantly skewed to T(H)2. J Allergy Clin Immunol. 2013 ;131:590-2.e1-6.
  3. Katsunuma T, Fujisawa T, Nagao M, Akasawa A, Nomura I, Yamaoka A, Kondo H, Masuda K, Yamaguchi K, Terada A, Ikeda M, Nishioka K, Adachi Y, Kurihara K.Effects of transdermal tulobuterol in pediatric asthma patients on long-term leukotriene receptor antagonist therapy: results of a randomized, open-label, multicenter clinical trial in Japanese children aged 4-12 years. Allergol Int. 2013;62:37-43.
  4. Kojima R, Matsuda A, Nomura I, Matsubara O, Nonoyama S, Ohya Y, Saito H, Matsumoto K. Salivary cortisol response to stress in young children with atopic dermatitis. Pediatr Dermatol. 2013;30:17-22.

2012

  1. Nomura I, Morita H, Ohya Y, Saito H, Matsumoto K. Non-IgE-mediated gastrointestinal food allergies: distinct differences in clinical phenotype between Western countries and Japan. Curr Allergy Asthma Rep. 2012;12:297-303.

2011

  1. Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A, Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ, Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K. Genome-wide Association Study Identifies HLA-DP as a Susceptibility Gene for Pediatric Asthma in Asian Populations. PLoS Genet. 2011;7:e1002170.
  2. Yamada Y, Nishi A, Ebara Y, Kato M, Yamamoto H, Morita H, Nomura I, Matsumoto K, Hirato J, Hatakeyama SI, Suzuki N, Hayashi Y. Eosinophilic gastrointestinal disorders in infants: a Japanese case series. Int Arch Allergy Immunol. 2011;155 Suppl 1:40-5.
  3. Nomura I, Morita H, Hosokawa S, Hoshina H, Fukuie T, Watanabe M, Ohtsuka Y, Shoda T, Terada A, Takamasu T, Arai K, Ito Y, Ohya Y, Saito H, Matsumoto K, Four distinct subtypes of non-IgE-mediated gastrointestinal food allergies in neonates and infants, distinguished by their initial symptoms. J Allergy Clin Immunol, 2011; 127(3): 685-8.e1-8.

Before 2010

  1. Fukuie T, Nomura I, Horimukai K, Manki A, Masuko I, Futamura M, Narita M, Ohzeki T, Matsumoto K, Saito H, Ohya Y.　Proactive treatment appears to decrease serum immunoglobulin-E levels in patients with severe atopic dermatitis. Br J Dermatol. 2010;163:1127-9.
  2. Nomura I, Abe J, Noma S, Saito H, Gao B, Wheeler G, Leung DY. Adrenomedullin Is Highly Expressed in Blood Monocytes Associated with Acute Kawasaki Disease: A Microarray Gene Expression Study. Pediatr Res 2005;57:49-55.
  3. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113:651-7. Review.
  4. Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, Leung DY. Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol. 2003;112:1195-202.
  5. Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003 15;171:3262-9.
  6. Nomura I, Katsunuma T, Tomikawa M, Shibata A, Kawahara H, Ohya Y, Abe J, Saito H, Akasawa A. Hypoproteinemia in severe childhood atopic dermatitis: a serious complication. Pediatr Allergy Immunol. 2002;13:287-94.
  7. Nomura I, Katsunuma T, Matsumoto K, Iida M, Tomita H, Tomikawa M, Kawahara H, Akasawa A, Pawankar R, Saito H. Human mast cell progenitors in peripheral blood from atopic subjects with high IgE levels. Clin Exp Allergy. 2001;31:1424-31.
  8. Nomura I, Tanaka K, Tomita H, Katsunuma T, Ohya Y, Ikeda N, Takeda T, Saito H, Akasawa A. Evaluation of the staphylococcal exotoxins and their specific IgE in childhood atopic dermatitis. J Allergy Clin Immunol. 1999;104:441-6.

診療ガイドライン、診断治療指針

  1. 新生児・乳児食物蛋白誘発胃腸症診療ガイドライン (Minds準拠) 厚生労働省好酸球性消化管疾患研究班、日本小児アレルギー学会、日本小児栄養消化器肝臓病学会　野村伊知郎、山田佳之、大塚宜一ほか、発行年月日　2018年5月25日 https://minds.jcqhc.or.jp/n/med/4/med0351/G0001047

  2. 新生児-乳児食物蛋白誘発胃腸炎（消化管アレルギー）診断治療指針 厚生労働省好酸球性消化管疾患研究班（研究代表者　野村伊知郎）作成　2017年11月11日 https://www.ncchd.go.jp/hospital/sickness/allergy/shokakan_shishin20171111.pdf

  3. 食物蛋白誘発胃腸炎 (FPIES) 国際診療ガイドライン Nowak-Węgrzyn A, Chehade M, Groetch ME, Spergel JM, Wood RA, Allen K, Atkins D, Bahna S, Barad AV, Berin C, Brown Whitehorn T, Burks AW, Caubet JC, Cianferoni A, Conte M, Davis C, Fiocchi A, Grimshaw K, Gupta R, Hofmeister B, Hwang JB, Katz Y, Konstantinou GN, Leonard SA, Lightdale J, McGhee S, Mehr S, Sopo SM, Monti G, Muraro A, Noel SK, Nomura I, Noone S, Sampson HA, Schultz F, Sicherer SH, Thompson CC, Turner PJ, Venter C, Westcott-Chavez AA, Greenhawt M. International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2017;139:1111-1126.

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