Molecular basis of primary immunodeficiency of antibody deficiency

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591020
• 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, University hospital, Assistant Professor, 医学部附属病院, 講師 (80293554)
• Co-Investigator(Kenkyū-buntansha): FUKAO Toshiyuki Gifu University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70260578)
• Project Period (FY): 2004 – 2005
• Keywords: primary immunodeficiency / IgA deficiency / CVID / IgA subclass / TACI / alpha germline transcript

Research Abstract

Selective IgA deficiency and common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, I alpha germline transcript expression levels decreased and alpha circle transcripts were not detected. Stimulation with PMA and TGF-beta1 up-regulated I alpha germline and alpha circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, I alpha germline, alpha circle transcripts and C alpha mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of I alpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.
In addition we established the assay system, which could detect the expression of IgA1 and IgA2 gene specifically. This assay system is useful for elucidating the pathogenesis of CVID and IgA deficiency.

Research Products

• [Journal Article] Leaky phenotype of X-linked agammaglobulinaemia in a Japanese family. (2005)
  • Author(s): Kaneko H, Kawamoto N, Asano T, Mabuchi Y, Horikoshi H, Teramoto T, Matsui E, Kondo M, Fukao T, Kasahara K, Kondo N
  • Journal Title: Clin Exp Immunol. 140 Pages: 520-523
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the Lennox-Gastaut syndrome. (2005)
  • Author(s): Kondo M, Fukao T, Teramoto T, Kaneko H, Takahashi Y, Okamoto H, Kondo N
  • Journal Title: Pediatric Allergy and Immunology 16 Pages: 357-360
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel single-nucleotide substitution, Glu 4 Lys, in the leukotriene C4 synthase gene associated with allergic diseases (2005)
  • Author(s): Yoshikawa K, Matsui E, Kaneko H, Fukao T, Inoue R, Teramoto T, Shinoda S, Fukutomi O, Aoki M, Kasahara K, Kondo N
  • Journal Title: Int J Mol Med. 16 Pages: 827-831
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IL-12B Promoter Polymorphism Associated with Asthma and IL-12B Transcriptional Activity (2005)
  • Author(s): Koji Tatebayashi, Eiko Matsui, Hideo Kaneko, Toshiyuki Fukao, Kimiko Kasahara, Naomi Kondo
  • Journal Title: Allergology International 3 Pages: 451-459
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Leaky phenotype of X-linked agammaglobulinaemia in a Japanese family. (2005)
  • Author(s): Kaneko H, Kawamoto N, Asano T, Mabuchi Y, Horikoshi H, Teramoto T, Matsui E, Kondo M, Fukao T, Kasahara K, Kondo N.
  • Journal Title: Clin Exp Immunol. 140 Pages: 520-523
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the Lennox-Gastaut syndrome. (2005)
  • Author(s): Kondo M, Fukao T, Teramoto T, Kaneko H, Takahashi Y, Okamoto H, Kondo N.
  • Journal Title: Pediatric Allergy and Immunology 16 Pages: 357-360
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NOVEL DEVELOPMENTS ON GENETIC RECOMBINATION : DNA DOUBLE STRAND BREAK AND DNA END-JOINING (2004)
  • Author(s): Kaneko H, Fukao T, Kondo N
  • Journal Title: Advances Biophysics 33 Pages: 45-64
  • 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.
  • Author(s): Kawamoto N, Kaneko H, Takemura M, Seishima M, Sakurai S, Fukao T, Kasahara K, Iwasa S, Kondo N
  • Journal Title: Pediatric Allergy and Immunology (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effect of dioxins on the quantitative kevels of immune components in infants.
  • Author(s): Kaneko H, Matsui E, Shinoda S, Kawamoto N, Nakamura Y, Uehara R, Matsuura N, Morita M, Tada H, Kondo N
  • Journal Title: Toxicology and Industrial Health (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Age-related changes in intracellular cytokine profiles and Th2 dominance in allergic children.
  • Author(s): Kawamoto N, Kaneko H, Takemura M, Seishima M, Sakurai S, Fukao T, Kasahara K, Iwasa S, 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] Effect of dioxins on the quantitative kevels of immune components in infants.
  • Author(s): Kaneko H, Matsui E, Shinoda S, Kawamoto N, Nakamura Y, Uehara R, Matsuura N, Morita M, Tada H, Kondo N.
  • Journal Title: Toxicology and Industrial Health (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] NOVEL DEVELOPMENTS ON GENETIC RECOMBINATION : DNA DOUBLE STRAND BREAK AND DNA END-JOINING (2004)
  • Author(s): Kaneko H, Fukao T, Kondo N
  • Total Pages: 45-64
  • Publisher: JAPAN SCIENTIFIC SOCIETIES PRESS ELSEVIER
  • Description: 「研究成果報告書概要(和文)」より