The diversity of clinical course and the pathogensis in primary antibody deficiency

• Project/Area Number: 23591535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: 独立行政法人国立病院機構長良医療センター(臨床研究部) (2013); Gifu University (2011-2012)
• Principal Investigator: KANEKO Hideo 独立行政法人国立病院機構長良医療センター(臨床研究部), その他部局等, その他 (80293554)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 抗体産生不全症 / ＸＬＡ / ＢＴＫ / ガンマグロブリン補充 / 骨髄炎 / 胸膜炎 / 皮下注 / 抗体産生不全 / EDA-ID / IKBA / XLA / 免疫不全症 / 高ＩｇＭ症候群 / Helicobacter equorum

Research Abstract

X-linked agammaglobulinemia (XLA) develops due to mutation of tyrosine kinase BTK gene essential for B-cell differentiation. We examined the long-term course of four cases in 2 XLA family. Family 1 had missense mutations (L111R) in the BTK gene. Proband was suffering from severe infection, such as pleurisy and osteomyelitis. He developed pleurisy as an opportunistic infection by Helicobacter bacteria. The abnormally high level of endotoxin persisted. In family 2 mutation of the splice donor site of the BTK gene (IVS11+3 G>T) caused the skipping of exon 11. Proband (38 years), have not developed serious infections. Cousin of the proband, are enforced at the home once a week gamma globulin subcutaneous injection. The susceptibility to infection is not observed in family 2. The clinical course was variable in any individual case even with enough trough IgG level.

Research Products

• [Journal Article] Total IgE at 6 months predicts remittance or persistence of atopic dermatitis at 14 months (2013)
  • Author(s): Kawamoto N, Fukao T, Kaneko H.(他13名)
  • Journal Title: Allergy Asthma Proc Volume: 34(4) Pages: 362-9
• [Journal Article] ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis (2013)
  • Author(s): Tanaka H, Shimazawa M, Takata M, Kaneko H. (他10名)
  • Journal Title: J Neurol Volume: 260(7) Pages: 1782-97
• [Journal Article] Peripheral blood stem cell transplantation in a significant body weight difference between a smaller donor and a larger recipient : A case report (2013)
  • Author(s): Funato M, Kaneko H, Sasai H, Kubota K, Ozeki M, Kanda K, Kato Z, Kondo N.
  • Journal Title: Transfus Apher Sci Volume: 49(3) Pages: 504-6
• [Journal Article] In vitro analysis of the functional effects of an NLRP3 G809S variant with the co-existence of MEFV haplotype variants in atypical autoinflammatory syndrome (2013)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Matsui E, Murase K, Kanoh H, Kato Z, Kaneko H, Seishima M, Kondo N.
  • Journal Title: J Clin Immunol Volume: 33(2) Pages: 325-34
• [Journal Article] Paclitaxel-based chemotherapy for aggressive kaposiform hemangioendothelioma of the temporomastoid region : Case report and review of the literature (2013)
  • Author(s): Funato M, Fukao T, Sasai H, Hori T, Terazawa D, Kanda K, Ozeki M, Mizuta K, Hirose Y, Kaneko H, Kondo N.
  • Journal Title: Head Neck Volume: 35(8)
• [Journal Article] 免疫不全を伴う特徴的な症候群―毛細血管拡張症、Bloom症候群― (2013)
  • Author(s): 金子英雄
  • Journal Title: 小児科診療 Volume: 76 Pages: 413-418
• [Journal Article] Good症候群(免疫不全症を伴う胸腺腫) (2013)
  • Author(s): 金子英雄
  • Journal Title: 別冊日本臨床血液症候群(第2版) Volume: No.22 Pages: 300-303
• [Journal Article] ブルーム(Bloom)症候群 (2013)
  • Author(s): 金子英雄
  • Journal Title: 別冊日本臨床血液症候群(第2版) Volume: No.22 Pages: 297-299
• [Journal Article] 小児食物アレルギーの自然経過と治療 (2013)
  • Author(s): 金子英雄
  • Journal Title: Monthly Book Derma Volume: 205 Pages: 69-76
• [Journal Article] 食物アレルギーにおける経口免疫療法 (2013)
  • Author(s): 金子英雄
  • Journal Title: 小児科診療 Volume: 5 Pages: 857-861
• [Journal Article] Total IgE at 6 months predicts remittance or persistence of atopic dermatitis at 14 months. (2013)
  • Author(s): Kawamoto N, Fukao T, Kaneko H, Hirayama K, Sakurai S, Arai T, Kondo M, Kawamoto M, Matsui E, Orii K, Kasahara K, Takemura M, Seishima M, Shiraki M, Iwasa S, Kondo N.
  • Journal Title: Allergy Asthma Proc. Volume: 34 Pages: 362-9
  • Peer Reviewed
• [Journal Article] ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis. (2013)
  • Author(s): Tanaka H.. Shimazawa M., Takata M., Kaneko H., Tsuruma K., Ikeda T., Warita H., Aoki M., Yamada M., Takahashi H., Hozumi I., Minatsu H., Inuzuka T. and Hara H.
  • Journal Title: Journal of Neurology Volume: (Epub ahead of print) Issue: 7 Pages: 1782-1797
  • DOI: 10.1007/s00415-013-6877-3
  • Peer Reviewed
• [Journal Article] Peripheral blood stem cell transplantation in a significant body weight difference between a smaller donor and a larger recipient: a case report. (2013)
  • Author(s): Funato M, Kaneko H, Sasai H, Kubota K, Ozeki M, Kanda K, Kato Z, Kondo N.
  • Journal Title: Transfus Apher Sci. Volume: 49 Issue: 3 Pages: 504-6
  • DOI: 10.1016/j.transci.2013.01.015
  • Peer Reviewed
• [Journal Article] In Vitro Analysis of the Functional Effects of an NLRP3 G809S Variant with the co-Existence of MEFV Haplotype Variants in Atypical Autoinflammatory Syndrome (2013)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Matsui E, Murase K, Kanoh H, Kato Z, Kaneko H, Seishima M, Kondo N
  • Journal Title: J Clin Immunol Volume: 33 Issue: 2 Pages: 325-34
  • DOI: 10.1007/s10875-012-9805-x
  • Peer Reviewed
• [Journal Article] Paclitaxel-based chemotherapy for aggressive kaposiform hemangioendothelioma of the temporomastoid region: Case report and review of the literature. (2013)
  • Author(s): Funato M, Fukao T, Sasai H, Hori T, Terazawa D, Kanda K, Ozeki M, Mizuta K, Hirose Y, Kaneko H, Kondo N.
  • Journal Title: Head Neck. Volume: 35 Issue: 8 Pages: 258-61
  • DOI: 10.1002/hed.23107
  • Peer Reviewed
• [Journal Article] 免疫不全を伴う特徴的な症候群 ―毛細血管拡張症、Bloom症候群― (2013)
  • Author(s): 金子英雄
  • Journal Title: 小児科診療 Volume: 76 Pages: 413-418
  • Peer Reviewed
• [Journal Article] Good症候群（免疫不全症を伴う胸腺腫） (2013)
  • Author(s): 金子英雄
  • Journal Title: 別冊日本臨床 血液症候群（第2版） Volume: 22 Pages: 300-303
  • Peer Reviewed
• [Journal Article] ブルーム(Bloom)症候群 (2013)
  • Author(s): 金子英雄
  • Journal Title: 別冊日本臨床 血液症候群（第2版） Volume: 22 Pages: 297-299
  • Peer Reviewed
• [Journal Article] In Vitro Analysis of the Functional Effects of an NLRP3 G809S Variant with the co-Existence of MEFV Haplotype Variants in Atypical Autoinflammatory Syndrome. (2013)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Matsui E, Murase K, Kanoh H, Kato Z, Kaneko H, Seishima M, Kondo N.
  • Journal Title: J Clin Immunol. Volume: 33 Pages: 325-34
  • Peer Reviewed
• [Journal Article] Paclitaxel-based chemotherapy for aggressive kaposiform hemangioendothelioma of the temporomastoid region: Case report and review of the literature. (2013)
  • Author(s): Funato M, Fukao T, Sasai H, Hori T, Terazawa D, Kanda K, Ozeki M, Mizuta K, Hirose Y, Kaneko H, Kondo N
  • Journal Title: Head Neck Volume: 35
  • Peer Reviewed
• [Journal Article] Peripheral blood stem cell transplantation in a significant body weight difference between a smaller donor and a larger recipient: A case report. (2013)
  • Author(s): Funato M, Kaneko H, Sasai H, Kubota K, Ozeki M, Kanda K, Kato Z, Kondo N.
  • Journal Title: Transfus Apher Sci. Volume: in press
  • Peer Reviewed
• [Journal Article] Repeated-dose pharmacokinetics of inhaled ciclesonide (CIC-HFA) in Japanese children with bronchial asthma : a phase I study (2012)
  • Author(s): Teramoto T, Kaneko H, (他9名)
  • Journal Title: Allergol Int Volume: 61(4) Pages: 619-24
  • NAID: 130004873052
• [Journal Article] Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism (2012)
  • Author(s): Hori T, Ohnishi H, Teramoto T, Tsubouchi K, Naiki T, Hirose Y, Ohara O, Seishima M, Kaneko H, Fukao T, Kondo
  • Journal Title: J Clin Immunol Volume: 32(6) Pages: 1213-20
• [Journal Article] Risk factors for infantile atopic dermatitis and recurrent wheezing (2012)
  • Author(s): Kawamoto N, Fukao T, Kaneko H, Hirayama K, Sakurai S, Arai T, Kondo M, Kawamoto M, Matsui E, Teramoto T, Kasahara K, Bai C, Zhang G, Omoya K, Matsukuma E, Morimoto M, Suzuki H, Aoki Y, Kimura T, Nada M, Morita H, Tokumi T, Takemura M, Seishima M, Shiraki M, Iwasa S, Kondo
  • Journal Title: J Investig Allergol Clin Immunol Volume: 22(2) Pages: 116-25
• [Journal Article] Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients (2012)
  • Author(s): Ohnishi H, Kaneko H,(他8名)
  • Journal Title: J Clin Immunol Volume: 32(2) Pages: 221-9
• [Journal Article] A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome (2012)
  • Author(s): Ohnishi H, Miyata R, Suzuki T, Nose T, Kubota K, Kato Z, Kaneko H, Kondo N.
  • Journal Title: J Allergy Clin Immunol Volume: 129(2) Pages: 578-80
• [Journal Article] Structural property of soybean protein P34 and specific IgE response to recombinant P34 in patients with soybean allergy (2012)
  • Author(s): Morita H, Kaneko H.(他9名)
  • Journal Title: Int J Mol Med Volume: 29(2) Pages: 153-8
• [Journal Article] Characterization of NLRP3 Variants in Japanese Cryopyrin-Associated Periodic Syndrome Patients. (2012)
  • Author(s): Ohnishi H, Teramoto T, Iwata H, Kato Z, Kimura T, Kubota K, Nishikomori R, Kaneko H, Seishima M, Kondo N
  • Journal Title: J Clin Immunol Volume: 32 Pages: 221-229
  • Peer Reviewed
• [Journal Article] A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome. (2012)
  • Author(s): Ohnishi H, Miyata R, Suzuki T, Nose T, Kubota K, Kato Z, Kaneko H, Kondo N
  • Journal Title: J Allergy Clin Immunol. Volume: 129 Pages: 578-580
  • Peer Reviewed
• [Journal Article] Structural property of soybean protein P34 and specific IgE response to recombinant P34 in patients with soybean allergy. (2012)
  • Author(s): Morita H, Kaneko H, Ohnishi H, Kato Z, Kubota K, Yamamoto T, Matsui E, Teramoto T, Fukao T, Kasahara K, Kondo N
  • Journal Title: Int J Mol Med Volume: 29 Pages: 153-158
  • Peer Reviewed
• [Journal Article] Risk factors for infantile atopic dermatitis and recurrent wheezing. (2012)
  • Author(s): Kawamoto N, Fukao T, Kaneko H, Hirayama K, Sakurai S, et al.,
  • Journal Title: J Investig Allergol Clin Immunol Volume: 22 Pages: 116-25
  • Peer Reviewed
• [Journal Article] Repeated-dose pharmacokinetics of inhaled ciclesonide (CIC-HFA) in Japanese children with bronchial asthma: a phase I study. (2012)
  • Author(s): Teramoto T, Matsui E, Fukao T, Sakai K, Yonezawa H, Kato Z, Ohnishi H, Kaneko H, Kondo N, Azuma J, Nishima S.
  • Journal Title: Allergol Int Volume: 61 Pages: 619-24
  • NAID: 130004873052
  • Peer Reviewed
• [Journal Article] Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism. (2012)
  • Author(s): Hori T, Ohnishi H, Teramoto T, Tsubouchi K, Naiki T, Hirose Y, Ohara O, Seishima M, Kaneko H, Fukao T, Kondo N
  • Journal Title: J Clin Immunol. Volume: 32 Pages: 1213-20
  • Peer Reviewed
• [Journal Article] A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome. (2012)
  • Author(s): Ohnishi H, Miyata R, Suzuki T, Nose T, Kubota K, Kato Z, Kaneko H, Kondo N
  • Journal Title: J Allergy Clin Immunol Volume: 129 Pages: 578-580
  • Peer Reviewed
• [Journal Article] Successful treatment of pediatric immune thrombocytopenic purpura associated with ulcerative colitis (2011)
  • Author(s): Funato M, Fukao T, Sasai H, Hori T, Terazawa D, Kubota K, Ozeki M, Orii K, Kaneko H, Kondo N.
  • Journal Title: Pediatr Int Volume: 53(5) Pages: 771-3
• [Journal Article] Pediatric acute lymphoblastic leukemia mimicking Henoch-Schönlein purpura (2011)
  • Author(s): Funato M, Kaneko H, Kubota K, Ozeki M, Kanda K, Orii K, Kato Z, Fukao T, Kondo .
  • Journal Title: Pediatr Int Volume: 53(5) Pages: 766-8
• [Journal Article] Refractory chronic pleurisy caused by Helicobacter equorum-like bacterium in a patient with X-linked agammaglobulinemia (2011)
  • Author(s): Funato M, Kaneko H, Ohkusu K, Sasai H, Kubota K, Ohnishi H, Kato Z, Fukao T, Kondo N.
  • Journal Title: J Clin Microbiol Volume: 49(9) Pages: 3432-5
• [Journal Article] Augmented cell death with Bloom syndrome helicase deficiency (2011)
  • Author(s): Kaneko H, Fukao T, Kasahara K, Yamada T, Kondo N.
  • Journal Title: Mol Med Rep Volume: 4(4) Pages: 607-9
• [Journal Article] Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis (2011)
  • Author(s): An Y, Ohnishi H, Matsui E, Funato M, Kato Z, Teramoto T, Kaneko H, Kimura T, Kubota K, Kasahara K, Kondo N.
  • Journal Title: Int J Mol Med Volume: 27(6) Pages: 795-801
  • NAID: 120006341946
• [Journal Article] Antigen-specific immune response to endotoxin-free recombinant P34 (2011)
  • Author(s): Morita H, Kaneko H, Ohnishi H, Kato Z, Kondo N.
  • Journal Title: Allergy Volume: 66(7) Pages: 985-6
• [Journal Article] Antigen-specific immune response to endotoxin-free recombinant P34. (2011)
  • Author(s): Morita H, Kaneko H, Ohnishi H, Kato Z, Kondo N
  • Journal Title: Allergy Volume: 66 Pages: 985-986
  • Peer Reviewed
• [Journal Article] Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis. (2011)
  • Author(s): An Y, Ohnishi H, Matsui E, Funato M, Kato Z, Teramoto T, Kaneko H, Kimura T, Kubota K, Kasahara K, Kondo N
  • Journal Title: Int J Mol Med Volume: 27 Pages: 795-801
  • NAID: 120006341946
  • Peer Reviewed
• [Journal Article] Augmented cell death with Bloom syndrome helicase deficiency. (2011)
  • Author(s): Kaneko H, Fukao T, Kasahara K, Yamada T, Kondo N
  • Journal Title: Mol Med Report Volume: 4 Pages: 607-609
  • Peer Reviewed
• [Journal Article] Refractory chronic pleurisy caused by Helicobacter equorum-like bacterium in a patient with X-linked agammaglobulinemia. (2011)
  • Author(s): Funato M, Kaneko H, Ohkusu K, Sasai H, Kubota K, Ohnishi H, Kato Z, Fukao T, Kondo N
  • Journal Title: J Clin Microbiol Volume: 49 Pages: 3432-3435
  • Peer Reviewed
• [Journal Article] Pediatric acute lymphoblastic leukemia mimicking Henoch-Schönlein purpura. (2011)
  • Author(s): Funato M, Kaneko H, Kubota K, Ozeki M, Kanda K, Orii K, Kato Z, Fukao T, Kondo N
  • Journal Title: Pediatr Int Volume: 53 Pages: 766-768
  • Peer Reviewed
• [Journal Article] Successful treatment of pediatric immune thrombocytopenic purpura associated with ulcerative colitis. (2011)
  • Author(s): Funato M, Fukao T, Sasai H, Hori T, Terazawa D, Kubota K, Ozeki M, Orii K, Kaneko H, Kondo N
  • Journal Title: Pediatr Int Volume: 53 Pages: 771-773
  • Peer Reviewed
• [Journal Article] A Complement Factor B Mutation in a Large Kindred with Atypical Hemolytic Uremic Syndrome
  • Author(s): Funato M, Uemura O, Ushijima K, Ohnishi H, Orii K, Kato Z, Yamakawa S, Nagai T, Ohara O,Kaneko H, Kondo N.
  • Journal Title: J Clin Immunol Volume: (in press)
• [Presentation] X-linked agammaglobulinemia 2家系の長期経過の検討 (2014)
  • Author(s): 金子英雄、舩戸道徳 、森田秀行 、舘林宏治 、下川祐子、丸田香奈子 、内田靖、神田康司、大西秀典 、近藤直実
  • Organizer: 日本小児科学会総会
  • Place of Presentation: 名古屋
• [Presentation] 異なる免疫グロブリンの発現を示したXLAの一家系 (2013)
  • Author(s): 金子英雄、森田秀行、川本典生、大西秀典、寺本貴英、近藤直実
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-19
• [Presentation] 常染色体優性遺伝形式が推測される分類不能型免疫不全症の1家系 (2013)
  • Author(s): 大西秀典、寺本貴英、川本典生、金子英雄、臼井新治、新井隆広、川尻美和、山岸篤至、加藤善一郎、深尾敏幸、近藤直実
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-19
• [Presentation] 牛乳アレルギーにおける抗原改変β―ラクトグロブリン作製と臨床応用の試み (2013)
  • Author(s): 金子英雄、大西秀典、川本典生、寺本貴英、松井永子、加藤善一郎、森田秀行、加藤晴彦、中埜拓、近藤直実
  • Organizer: 第25回日本アレルギー学会春期臨床大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-05-12
• [Presentation] 異なる免疫グロブリンの発現を示したXLAの一家系 (2013)
  • Author(s): 金子英雄 、森田秀行、川本典生 、大西秀典 、寺本貴英 、近藤直実
  • Organizer: 日本小児アレルギー学会
  • Place of Presentation: 横浜
• [Presentation] 本邦におけるBloom症候群の実態調査 (2012)
  • Author(s): 金子英雄、内田靖、大西秀典、深尾敏幸、谷内江昭宏、清河信敬、滝田順子、山崎直也、田内久道、近藤直実
  • Organizer: 第４９回日本小児アレルギー学会
  • Place of Presentation: 大阪
• [Presentation] Pathogenesis and clinical feature of primary antibody deficiencies (2011)
  • Author(s): Kaneko H, Ohnishi H, Funato M, Kondo N
  • Organizer: The 7th Congress of Asian Society for Pediatric Research(招待講演)
  • Place of Presentation: Denver, USA
• [Presentation] Development of enzymatically digested peptides for immunomodulation therapy in patients with cow's milk allergy (2011)
  • Author(s): Kaneko H, Ohnishi H, Morita H, Yamamoto T, Kubota K, Teramoto T, Kato Z, Matsui E, Kato H, Nakano T, Kondo N
  • Organizer: 16th Asia Pacific Association of Pediatric Allergy, Respiratory and Immunology
  • Place of Presentation: Fukuoka, Japan
• [Book] DNA修復障害(近藤直実、平家俊男編集)自己炎症性疾患・自然免疫不全症とその近縁疾患 (2012)
  • Author(s): 金子英雄, 他
  • Publisher: 診断と治療社
• [Book] 色素脱失を伴う免疫不全症 自己炎症性疾患・自然免疫不全症とその近縁疾患 編集 近藤直実、平家俊男 (2012)
  • Author(s): 金子英雄
  • Publisher: 診断と治療社
• [Book] DNA修復障害 自己炎症性疾患・自然免疫不全症とその近縁疾患 編集 近藤直実、平家俊男 (2012)
  • Author(s): 金子英雄
  • Total Pages: 248
  • Publisher: 診断と治療社
• [Book] 毛細血管拡張性小脳失調症(ataxia-telangiectasia) 自己炎症性疾患・自然免疫不全症とその近縁疾患 編集 近藤直実、平家俊男 (2012)
  • Author(s): 金子英雄
  • Publisher: 診断と治療社
• [Book] Bloom症候群 自己炎症性疾患・自然免疫不全症とその近縁疾患 編集 近藤直実、平家俊男 (2012)
  • Author(s): 金子英雄
  • Publisher: 診断と治療社
• [Book] 食物アレルギーに対する抗原改変牛乳による経口免疫療法 アレルギー疾患の免疫療法と分子標的療法―理論と実践 (2012)
  • Author(s): 金子英雄、大西秀典、近藤直実
  • Publisher: 診断と治療社
• [Book] 症候群ハンドブック (2011)
  • Author(s): 金子英雄: 井村裕夫総編集
  • Total Pages: 2
  • Publisher: 東京 中山書店
• [Patent(Industrial Property Rights)] Th2サイトカイン阻害剤への感受性の検査方法 (2012)
  • Inventor(s): 近藤直実、松井永子、金子英雄、青木美奈子、近藤應
  • Industrial Property Rights Holder: 近藤直実、松井永子、金子英雄、青木美奈子、近藤應
  • Acquisition Date: 2012-04-20
  • Overseas