Fc receptor gene analysis and immunotherapy with bispecific antibody for periodontal disease

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12557191
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Periodontal dentistry
• Research Institution: NIIGATA UNIVERSITY
• Principal Investigator: YOSHIE Hiromasa NIIGATA UNIVERSITY Graduate School of Medical and Dental Sciences Professor, 大学院・医歯学総合研究科, 教授 (20143787)
• Co-Investigator(Kenkyū-buntansha): SUGITA Noriko Graduate School of Medical and Dental Sciences Assistant, 大学院・医歯学総合研究科, 助手 (30313547) ; KOBAYASHI Tetsuo Dental Hospital Lecturer, 歯学部附属病院, 講師 (00215344)
• Project Period (FY): 2000 – 2002
• Keywords: Fc receptor / Bispecific antibody / Immunothearpy / Periodonlal disease / r40kDa OMP / Porphyromonas gingivalis / Neutrophils

Research Abstract

- Diagnosis of periodontisis risk with Fc receptor gene polymorphisms :
The association of FcR polymorphisms with severity of chronic periodontitis (CP) was examined by means of allele-specific polymerase chain reactions. A significant over-representation of FcRIIIa-158V allele in severe CP patients as compared to moderate AP patients (P = 0.03). In addition, we found a strong association between CP severity and FcR composite genotype comprising FcRIIIA-158V plus FcRIIIB-NA2 (odds ratio 4.7, P = 0.002). The association study consisted of 60 SLE patients, age-matched 42 healthy subjects with periodontitis, and 42 healthy subjects without periodontitis indicated FcγRIIa-R131 allele to be a common risk factor for SLE and periodontitis. Variation screening of neutrophil-specific FcRIIIB and B cell-specific FcRIIB genes showed new one and seven single nucleotide polymorphisms, respectively, and documented the association of FcRIIB nt 775T/C with aggressive periodontitis risk. These results suggest FcR genotype to be associated with susceptibility to periodontitis.
- Immunotherapy of periodontitis with human monoclonal antibody :
Human immunoglobulin (Ig)-producing mice were immunized by intraperitoneal injection of recombinant 40-kDa outer membrane protein (r40-kDa OMP) of Porphyromonas gingivalis. Total 99 clones of human monoclonal antibodies (hMAb) specific for r40-kDa OMP were obtained, all of which was IgG isotype (IgG1 : 84 clones ; IgG2 : 11 clones ; IgG4 : 4 clones). The binding activity of hMAb to r40-kDa OMP was shown to be almost same as that of human polyclonal antibody (60 times higher in concentration). The opsonophagocytic activity of hMAb clones were also indicated to be almost same as that of human polyclonal antibody (10000 times higher in concentration). This hMAb was shown to enhance neutrophil phagocytosis of P. gingivalis.

Research Products

• [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)
  • Description: 「研究成果報告書概要(和文)」より
• [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
• [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)
  • Description: 「研究成果報告書概要(和文)」より
• [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
• [Publications] Keiko Yasuda et al.: "Seven single nucleotide substitutions in human Fcγ receptor I IB gene"Tissue Antigens. Vol.58, No.5. 339-342 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [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)
  • Description: 「研究成果報告書概要(和文)」より
• [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
• [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
• [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
• [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
• [Publications] K. Yasuda, N. Sugita, K. Yamamoto, 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
• [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