The mechanism of antibody production using the model of primary immunodeficiency, especially IgA deficiency

• Project/Area Number: 18591188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: KANEKO Hideo Gifu University, Graduate School of Medicine, Associate Professor (80293554)
• Co-Investigator(Kenkyū-buntansha): FUKAO Toshiyuki Gifu University, Graduate School of Medicine, Professor (70260578)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: CVI / IgA deficiency / TNF family / TNFR family / IgA subclass / APRIL / BAFF / lgA損症 / lgAサブクラス

Research Abstract

IgA deficiency (IgAD) is the most common immunodeficiency, but the pathogenesis of most cases of IgAD is poorly understood. The gene and protein expression levels of members of the IgA subclasses in IgAD patients were analyzed by a reverse transcriptase (RT) -PCR method that could differentiate between α 1 and α 2 gene expression. Three selective, 5 partial and 2 secondary IgAD patients were examined. Peripheral blood mononuclear cells that were unstimulated or stimulated with TGF- β 1 and PMA for 24 hours were cultured. The IgAl/IgA2 expression ratios were measured by zone densitometry. Three bands appeared (the α 1 and α2 genes, and a hetero-duplex formation), owing to the difference of 39 bases between α 1 and α2 mRNAs. In controls, there were no significant differences in the IgAl/IgA2 ratios between unstimulated and stimulated cells. In selective IgAD patients, both α1 and α2 gene expression were induced following stimulation, and α1 gene expression was induced more dominantly than in the other IgAD patients following stimulation. Based on our results, it was thought that suppression of α 1 gene expression may be related to the pathogenesis of IgAD.

Research Products

• [Journal Article] Age-related changes in BAFF and APRIL profiles and up-regulated BAFF and APRIL expression in patients with primary antibody deficiency. (2008)
  • Author(s): Jin R, Kaneko H, Suzuki H, Arai T, Teramoto T, Fukao T, Kondo N
  • Journal Title: Int J Mol Med 21 Pages: 233-238
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Induction of α1 and α2 gene expression in selective IgA deficiency. (2008)
  • Author(s): Suzuki H, Kaneko H, Rong J, Kawamoto N, Asano T, Matsui E, Kasahara K, Kondo N,
  • Journal Title: Molecular Medicine Report 1 Pages: 395-399
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Age-related changes in BAFF and APRIL profiles and up-regulated BAFF and APRIL expression in patients with primary antibody deficiency (2008)
  • Author(s): Jin, R., Kaneko, H., Suzuki, H., Arai, T., Teramoto, T., Fukao, T., Kondo, N
  • Journal Title: Int J Mol Med 21 Pages: 233-238
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of α1 and α2 gene expression in selective IgA deficiency (2008)
  • Author(s): Suzuki, H., Kaneko, H., Rong, J., Kawamoto, N., Asano, T., Matsui, E., Kasahara, K., Kondo, N
  • Journal Title: Molecular Medicine Report 1 Pages: 395-399
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Refractory osteomyelitis caused by bacille Calmette-Guerin vaccination: a case report. (2007)
  • Author(s): Funato M, Kaneko H, Matsui E, Teramoto T, Kato Z, Fukao T, Okusu K, Kondo N
  • Journal Title: Diagn Microbiol Infect Dis. 59 Pages: 89-91
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A positive Donath-Landsteiner test in paroxysmal cold haemoglobinuria. (2007)
  • Author(s): Funato M, Kaneko H, Ozeki M, Suzuki H, Orii K, Teramoto T, Fukao T, Kondo N
  • Journal Title: Eur J Haematol. 76 Pages: 462-462
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Clinical improvement of diffuse Iymphangiomatosis with pegylated interferon alfa-2b therapy: case report and review of the literature. (2007)
  • Author(s): Ozeki M, Funato M, Kanda K, Ito M, Teramoto T, Kaneko H, Fukao T, Kondo N
  • Journal Title: Pediatr Hematol Oncol. 24 Pages: 513-24
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Lymphcyte Responses to Chymotrypsin-or Trypsin V-Digested β-Lactoglobulin in Patients with Cow's Milk Allergy. (2007)
  • Author(s): Kondo M, Fukao T, Shinoda S, Kawamoto N, Kaneko H, Kato Z, Matsui E, Teramoto T, Nakano T, Kondo N.
  • Journal Title: Allergy, Asthma, and Clinical Immunology 3 Pages: 1-9
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Toll-like receptor signaling is impaired in dendritic cell from patients with X-linked agammaglobulinemia. (2007)
  • Author(s): Taneichi H, Kanegane H, Sira MM, Futatani T, Agematsu K, Sako M, Kaneko H, Kondo N, Kaisho T, Miyawaki T.
  • Journal Title: Clinical Immunoligy 126 Pages: 148-154
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Identification of Ali-mediated, large deletion-spanning introns 19-26 in PHKA2 in a patient with X-linked liver glycogenosis(hepatic phosphorylase kinase deficiency). (2007)
  • Author(s): Fukao T, Zhang G, Aoki Y, Arai T, Teramoto T, Kaneko H, Sugie H, Kondo N
  • Journal Title: Molecular Genetics and Metabolism 92 Pages: 179-182
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Refractory osteomyelitis caused by bacille Calmette-Gudrin vaccination : a case report (2007)
  • Author(s): Funato, M., Kaneko, H., Matsui, E., Teramoto, T., Kato, Z., Fukao, T., Okusu, K., Kondo, N
  • Journal Title: Diagn Microbiol Infect Dis 59 Pages: 89-91
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A positive Donath-Landsteiner test in paroxysmal cold haemoglobinuria (2007)
  • Author(s): Funato, M., Kaneko, H., Ozeki, M., Suzuki, H., Orii, K., Teramoto, T., Fukao, T., Kondo, N
  • Journal Title: Eur J Haematol 76 Pages: 462-462
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical improvement of diffuse lymphangiomatosis with pegylated interferon alfa-2b therapy : case report and review of the literature (2007)
  • Author(s): Ozeki, M., Funato, M., Kanda, K., Ito, M., Teramoto, T., Kaneko, H., Fukao, T., Kondo N
  • Journal Title: Pediatr Hematol Oncol 24 Pages: 513-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lymphcyte Responses to Chymotrypsin-or Trypsin V-Digested β-Lactoglobulin in Patients with Cow's Milk Allergy (2007)
  • Author(s): Kondo, M., Fukao, T., Shinoda, 5., Kawamoto, N., Kaneko, H., Kato, Z., Matsui, E., Teramoto, T., Nakano, T., Kondo, N
  • Journal Title: Allergy, Asthma, and Clinical Immunology 3 Pages: 1-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Toll-like receptor signaling is impaired in dendritic cell from patients with X-linked agammaglobulinemia (2007)
  • Author(s): Taneichi, H., Kanegane, H., Sira, MM., Futatani, T., Agematsu K., Sako, M., Kaneko, H., Kondo, N., Kaisho, T., Miyawaki, T
  • Journal Title: Clinical Immunology 126 Pages: 148-54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of Ali-mediated, large deletion-spanning introns 19-26 in PHKA2 in a patient with X-linked liver glycogenosis (hepatic phosphorylase kinase deficiency) (2007)
  • Author(s): Fukao, T., Zhang, G., Aoki, Y., Arai, T., Teramoto, T., Kaneko, H., Sugie, H., Kondo, N
  • Journal Title: Molecular Genetics and Metabolism 92 Pages: 179-182
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Refractory osteomyelitis caused by bacille Calmette-Guerin vaccination: a case report. (2007)
  • Author(s): Funato M, Kaneko H. Matsui E. Teramoto T, Kato Z, Fukao T, Okusu K, Kondo N
  • Journal Title: Diagn Microbiol Infect Dis. 59 Pages: 89-91
  • Peer Reviewed
• [Journal Article] Clinical improvement of diffuse lymphangiomatosis with pegylated interferon alfa-2b therapy: case report and review of the literature. (2007)
  • Author(s): Ozeki M, Funato M, Kanda K, Ito M, Teramoto T, Kaneko H, Fukao T, Kondo N
  • Journal Title: Pediatr Hematol Oncol. 24 Pages: 513-24
  • Peer Reviewed
• [Journal Article] Lymphcyte Responses to Chymotrypsin-or Trypsin V-Digested β-Lactoglobulin in Patients with Cow's Milk Allergy. (2007)
  • Author(s): Kondo M, Fukao T. Shinoda S, Kawamo to N, Kaneko H. Kato Z, Matsui E, Teramoto T, Nakano T, Kondo N.
  • Journal Title: Allergy, Asthma, and Clinical Immunology 3 Pages: 1-9
  • Peer Reviewed
• [Journal Article] Identification of Ali-mediated, large deletion-spanning introns 19-26 in PHKA2 in a patient with X-linked liver glycogenosis (hepatic phosp horylase kinase deficiency). (2007)
  • Author(s): Fukao T, Zhang G, Aoki Y, Arai T, Teramoto T, Kaneko H, Sugie H, Kondo N
  • Journal Title: Molecular Genetics and Metabolism 92 Pages: 179-182
  • Peer Reviewed
• [Journal Article] Human Tyk2 deficiency reveals requisite roles of Tyk2 in multiple cytokine signals involved in innate and acquired immunity. (2006)
  • Author(s): Minegishi Y, Kaneko H, et. al.,
  • Journal Title: Immunity 25 Pages: 745-755
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Autologous peripheral blood stem cell transplantation in a patient with relapsed pleuropulmonary blastoma. (2006)
  • Author(s): Kaneko H, et. al.,
  • Journal Title: Journal of Pediatric Hematology and Oncology 28 Pages: 383-385
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Suppression of IFN-gamma production in atopic group at the acutephase of RSV infection (2006)
  • Author(s): Kaneko H, et. al.,
  • Journal Title: Pediatric Allergy and Immunology 17 Pages: 370-375
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Human Tyk2 deficiency reveals requisite roles of Tyk2 in multiple cytokine signals involved in innate and acquired immunity (2006)
  • Author(s): Minegishi, Y., Kaneko, H., et. al.
  • Journal Title: Immunity 25 Pages: 745-755
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Suppression of IFN-gamma production in atopic group at the acute phase of RSV infection (2006)
  • Author(s): Kaneko, H., et. al.
  • Journal Title: Pediatric Allergy and Immunology 17 Pages: 370-375
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Age-related changes in intracellular cytokine profiles and Th2 dominance in allergic children. (2006)
  • Author(s): Kawamoto N, Kaneko H, ett al.
  • Journal Title: Pediatric Allergy and Immunology 17 Pages: 125-133
• [Journal Article] Effect of dioxins on the quantitative levels of immune components ininfants. (2006)
  • Author(s): Kaneko H, et al.
  • Journal Title: Toxicology and Industrial Health 22 Pages: 131-136
• [Journal Article] Suppression of IFN-gamma production in atopic group at the acute phase of RSV infection (2006)
  • Author(s): Kaneko H et al.
  • Journal Title: Pediatric Allergy and Immunology 17 Pages: 370-375
• [Journal Article] Autologous peripheral blood stem cell transplantation in a patient with relapsed pleuropulmonary blastoma. (2006)
  • Author(s): Kaneko H at al.
  • Journal Title: Journal of Pediatric Hematology and Oncology 28 Pages: 383-385
• [Journal Article] Human Tyk2 deficiency reveals requisite roles of Tyk2 in multiple cytokine signals involved in innate and acquired immunity. (2006)
  • Author(s): Minegishi Y, Kaneko H, et al.
  • Journal Title: Immunity 25 Pages: 745-755
• [Journal Article] The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitutions of T-cell core epitope
  • Author(s): Kondo M, Kaneko H, Fukao T, Suzuki K, Sakaguchi H, Shinoda S, Kato Z, Matsui E, Teramoto T, Nakano T, Kondo N.
  • Journal Title: Pediatric Allergy and Immunology (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Autologous peripheral blood stem cell transplantation in a patient with relapsed pleuropulmonary blastoma
  • Author(s): Kaneko, H., at al
  • Journal Title: Journal of Pediatric Hematology and Oncology
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitutions of T-cell core epitope
  • Author(s): Kondo, M., Kaneko, H., Fukao, T., Suzuki, K., Sakaguchi, H., Shinoda, S., Kato, Z., Matsui, E., Teramoto, T., Nakano, T., Kondo, N
  • Journal Title: Pediatric Allergy and Immunology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitutions of T-cell core epitope
  • Author(s): Kondo M, Kaneko H, Fukao T, Suzuki K, Sakaguchi H, Shinoda S, Kato Z, Matsui E, Teramoto T, Nakano T, Kondo N.
  • Journal Title: Pediatric Allergy and Immunology (In press)
  • Peer Reviewed
• [Journal Article] Induction of α1 and α2 gene expression in selective IgA deficiency.
  • Author(s): Suzuki H, Kaneko H, Rong J, Kawamoto N, Asano T, Matsui E, Kasahara K, Kondo N,
  • Journal Title: Molecular Medicine Report (In press)
  • Peer Reviewed
• [Presentation] IgA欠損症の病態と病因遺伝子の解析. (2007)
  • Author(s): 金子英雄, 鈴木啓子, 金 栄, 川本典生, 深尾敏幸, 松井永子, 青木美奈子, 新井隆広, 名田匡利, 近藤直実
  • Organizer: 日本小児科学会学術集会(第110回)
  • Place of Presentation: 京都
  • Year and Date: 2007-04-21
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Analysis of the causative genes for IgA deficiency (2007)
  • Author(s): Kaneko, H., Suzuki, H., Hong, J., Kawamoto, N., Fukao, T., Matsui, E., Aoki, M., Arai, T., Nada, M., Kondo, N
  • Organizer: The 110th annual meeting of the Japan Pediatric Society
  • Place of Presentation: Kyoto
  • Description: 「研究成果報告書概要(欧文)」より