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Genetic diagnosis and immunoglobulin A receptor targeting therapy for periodontitis

Research Project

Project/Area Number 13557189
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Periodontal dentistry
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

KOBAYASHI Tetsuo  NIIGATA UNIVERSITY, Medical and Dental Hospital, Lecturer, 医歯学総合病院, 講師 (00215344)

Co-Investigator(Kenkyū-buntansha) SUGITA Noriko  NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (30313547)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2003: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsPeriodontitis / Polymorphism / Immunoglobulin / FcαR / Bispecific antibody / Porphyromonas gingivalis / Neutrophils / Targeting therapy / 免疫グロブリンA / ターゲッテイング療法 / r40kDa OMP / Porhyromomas gingivalis
Research Abstract

-1.Genetic diagnosis of periodontisis risk :
Sequence analyses of immunoglobulin A and G Fc receptor (neutrophil-specific FcαRI, CD89 and B cell-specific FcγRIIB, CD32) indicated one and seven single-nucleotide substitutions, respectively. Of these polymorphisms, FcαRI nt 324A/G and FcγRIIB nt 775T/C have been shown to be associated with aggressive periodontitis risk. Neutrophils (PMN) from peripheral blood and gingival crevicular fluid (GCF) of periodontitis patients exhibited a decreased phagocytosis in the nt 324 A/A as compared to the nt 324 G/G patients. These results suggest FcαRI nt 324A/A patients to be high-susceptibility to aggressive periodontitis.
-2.Immunoglobulin A receptor targeting therapy :
The bispecific antibody (BsAb) was constructed from anti-Porphyromonas gingivalis and anti-FcαRI monoclonal antibody (MAb). Flow cytometric analyses showed opsonic activity for GCF PMN to be comparable between BsAb and control anti-P. gingivalis MAb. However, a BsAb significantly promoted phagocytosis and killing activity of GCF PMN, which exhibiting higher FcαRI expression levels than PB PMN. These data suggest BsAb targeting toward GCF PMN FcαRI to be effective for improvement of antibacterial immunity in periodontitis patients.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Tetsuo Kobayashi et al.: "Risk of Periodontitis in Systemic Lupus Erythematosus is Associated with Fcγ Receptor Polymorphisms"Journal of Periodontology. Vol.74. 378-384 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Keiko Yasuda et al.: "FcγRIIB Gene Polymorphisms in Japanese Periodontitis Patients"Genes and Immunity. Vol.4. 541-546 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kouji Yamamoto et al.: "Association of Fcγ receptor IIa genotype with chronic periodontitis in Caucasians"Journal of Periodontology. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Susumu Kaneko et al.: "A novel polymorphism of FcαRI (CD89) associated with aggressive periodontitis"Tissue Antigens. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuko Shimada et al.: "Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis"Journal of Clinical Periodontology. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gonzales JR et al.: "Interleukin-4 gene polymorphisms in Japanese and Caucasian patients with aggressive periodontitis"Journal of Clinical Periodontology. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kobayashi, S.Ito, K.Yamamoto, H.Hasegawa, N.Sugita, T.Kuroda, S.Kaneko, I.Narita, K.Yasuda, M.Nakano, F.Gejyo, H.Yoshie.: "Risk of Periodontitis in Systemic Lupus Erythematosus Is Associated with Fcγ Receptor Polymorphisms.."Journal of Periodontology. Vol.74, No.3. 378-384 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Yasuda, N.Sugita, K.T.Kobayashi, Yamamoto, H.Yoshie: "Seven single nucleotide substitutions in human Fcγ receptor IIB gene."Genes and Immunity. Vol.4, No.8. 541-546 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Yamamoto, T.Kobayashi, S.Grossi, AW.Ho, R.J.Genco, H.Yoshie, E.De Nardin.: "Association of Fcγ receptor IIa genotype with chronic periodontitis in Caucasians"Journal of Periodontology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Kaneko, T.Kobayashi, K.Yamamoto, M.D.Jansen, J.G.J.van de Winkel, H.Yoshie.: "Anovel polymorphism of FcαRI (CD89) associated with aggressive periodontitis."Tissue Antigens. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y, Shimada, H.Tai, M.Endo, T.Kobayashi, K.Akazawa, K.Yamazaki, H.Yoshie: "Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodicities"Journal of Clinical Periodontology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] JR.Gonzales, T.Kobayashi, J.Michel, M.Mann, H.Yoshie, J.Meyle: "Interleukin-4 gene polymorphisms in Japanese and Caucasian patients with aggressive periodontitis"Journal of Clinical Periodontology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tetsuo Kobayashi et al.: "Risk of Periodontitis in Systemic Lupus Erythematosus is Associated with Fcγ Receptor Polymorphisms"Journal of Periodontology. Vol.74,No.3. 378-384 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Keiko Yasuda et al.: "FcγRIIB Gene Polymorphisms in Japanese Periodontitis Patients"Genes and Immunity. Vol.4,No.8. 541-546 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Gonzales JR et al.: "Interleukin-4 gene polymorphisms in Japanese and Caucasian patients with aggressive periodontitis"Journal of Clinical Periodontology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kouji Yamamoto et al.: "Association of Fcγ receptor IIa genotype with chronic periodontitis in Caucasians"Journal of Periodontology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuko Shimada et al.: "Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis"Journal of Clinical Periodontology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Susumu Kaneko et al.: "A novel polymorphism of FcαRI (CD89) associated with aggressive periodontitis"Tissue Antigens. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tetsuo Kobayashi, et al.: "Effective In Vitoro Clearance of Porphyromonasgingivalis by Fcα Receptor I(CD89) on Gingival Crevicular Neutrophils"Infection and Immunity. Vol.69,No.5. 2935-2942 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tetsuo Kobayashi, et al.: "The Fcγ Receptor Genotype as a Severity Factor for Chronic Periodontitis in Japanese Patients"Journal of Periodontology. Vol.72,No.10. 1324-1331 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noriko Sugita, et al.: "Increased Frequency of FcγRIIIb-NA1 Allele in Periodontitis-resistant Subjects in an Elderly Japanese Population"Journal of Dental Research. Vol.80,No.3. 914-918 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kouji Yamamoto, et al.: "Evidence for a novel polymorphism affecting both N-linked glycosylation and ligand binding of the IgG receptor IIIB(CD16)"Tissue Antigens. Vol.57,No.4. 363-366 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Keiko Yasuda, et al.: "Seven single nucleotide substitutions in human Fcγ receptor IIB gene"Tissue Antigens. Vol.58,No.5. 339-342 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tetsuo Kobayashi, et al.: "Risk of Periodontitis in Systemic Lupus Erythematosus is Associated with Fcγ Receptor Polymorphisms"Journal of Periodontology. Vol.74,No.3. 378-384 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tetsuo Kobayashi et al.: "Effective In Vitro Clearance of Porphyromonas gingivalis by Fcα Receptor I (CD89) on Gingival Crevicular Neutrophils"Infection and Immunity. Vol.69, No.5. 2935-2942 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tetsuo Kobayashi et al.: "The Fcγ Receptor Genotype as a Severity Factor for Chronic Periodontitis in Japanese Patients"Journal of Periodontology. Vol.72, No.10. 1324-1331 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noriko Sugita et al.: "Increased Frequency of FcγIIIb-NA 1 Allele in Periodontitis-resistant Subjects an Elderly Japanese Population"Journal of Dental Research. Vol.80, No.3. 914-918 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kouji Yamamoto et al.: "Evidence for a novel polymorphism affecting both N-linked glycosylation and ligand binding of the IgG receptor IIIB (CD 16)"Tissue Antigens. Vol.57, No.4. 363-366 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Keiko Yasuda et al.: "Seven single nucleotide substitutions in human Fcγ receptor IIB gene"Tissue Antigens. Vol.58, No.5. 339-342 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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