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

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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.