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

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- 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.