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Development of Immunotherapy of Refractory Periodontitis with Anti-Fc Receptor Bispecific Antibodies

Research Project

Project/Area Number 12672032
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontal dentistry
Research InstitutionNiigata University

Principal Investigator

KOBAYASHI Tetsuo  Dental Hospital, Niigata University, Lecturer, 歯学部・附属病院, 講師 (00215344)

Co-Investigator(Kenkyū-buntansha) SUGITA Noriko  Graduate School of Medical and Dental Sciences, Niigata University, Assistant, 大学院・医歯学総合研究科, 助手 (30313547)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsFc receptor / Immunoglobulin / Porphyromonas gingivalis / r40kDa OMP / Human monoclonal antibodies / Neutrophils / Opsonophagocytosis / オプソニン化 / bispecific抗体 / 免疫療法 / 歯周炎 / 歯肉溝滲出液
Research Abstract

After informed consent was obtained, gingival crevicular fluid (GCF)- and peripheral blood (PB)-neutrophils (PMN) from 21 adult periodohtitis patients were analyzed for their IgG and IgA PcR (FcγR and FcαR) expression and function by studying IgG- and IgA-mediated elimination of Porphyromonas gingivalis. GCF-PMN exhibited increased FcαR levels and decreased FcγR levels compared to PB-PMN. Functional studies revealed GCF-PMN to exhibit a decreased capacity to phagocytose and kill IgG1-opsonized P.gingivalis compared to PB-PMN. IgA1-mediated phagocytosis and killing capacity was, however, comparable between GCF- and PB-PMN. These results suggest FcαR to represent a candidate target for FcR-directed immunotherapy of periodontitis.
Recombinant 40-kDa outer membrane protein (rOMP-40) of P. gingivalis was obtained by purification with homogeneity from the cell sonicate. Human immunoglobulin producing mice, KM mouse^<TM>, were immunized by injection of rOMP-40. The spleen cells were collected, and then fused with the mouse myeloma cell line. Total 102 clones of human mononlonal antibodies (hMAbs) specific for rOMP-40 were obtained and screened by enzyme-linked immunosorbent assay. The number of IgG was 99, whereas three were IgM. IgA clone was not established. The opsonophagocytic activity of hMAb clones showing high reactivity with rOMP-40 was measured. Our results indicated hMAb clones to be significantly higher in opsonophagocytic activity than human polyclonal antibodies. These results provided the possibility that topical application of hMAbs would be aid in PMN-dependent elimination of P. gingivalis.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Noriko Sugita et al.: "Increased Frequency of FcγRIIIb-NA1 Allele in Periodontitis-resistant Subjects in an Elderly Japanese Population"Journal of Dental Rescarch. Vol.80, No.3. 914-918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Keiko Yasuda et al.: "Seven single nuclcotide substitutions in human Fcγ receptor HB gene"Tissue Antigens. Vol.58, No.5. 339-342 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kobayashi, K. Yamamoto, N. Sugita, A.B. van Spriel, S. Kaneko, J. G. J. van de Winkel, H. Yoshie: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kobayashi, K. Yamamoto, N. Sugita, W-L. van der Pol, K. Yasuda, S. Kaneko, J.G.J. van de Winkel, H. Yoshie: "The Fcγ Receptor Genotype as a Severity Factor for Chronic Periodontitis in Japanese Patients"Journal of Periodontology. Vol. 72, No. 10. 1324-1331 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Sugita, T. Kobayashi, Y. Ando, A. Yoshihara, K. Yamamoto, J.G.J. van de Winkel, H. Miyazaki, H. Yoshie: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Yamamoto, N. Sugita, T. Kobayashi, K. Okuda, J. G.J. van de Winkel, H. Yoshie: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Yasuda, N. Sugita, K. Yamaimoto, T. Kobayashi, H. Yoshie: "Seven single nucleotide substitutions in human Fcγ receptor IIB gene"Tissue Antigens. Vol. 58, No. 5. 339-342 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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 as 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 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
      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 (CD16)"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
  • [Publications] Tetsuo Kobayashi et al.: "Effective In Vitro clearance of Porphyromonas gingivalis by FcαRI (CD89) on gingival crevicular neutrophils"Infection and Immunity. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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