OC-STAMP-reactive IgG auto-antibody may upregulate osteoclastogenesis in association with elevated anti-<i>P. gingivalis</i>antibody

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objectives:</jats:title> <jats:p>Periodontal disease (PD) is a polymicrobial inflammatory lesion in which pathogenic bone loss is caused by osteoclasts (OC) differentiated from MCSF/RANKL-primed monocytes. Elevated IgG antibody to a keystone opportunistic pathogen, Porphyromonas gingivalis (Pg), is a hallmark humoral response in PD that is correlated with pathogenic bone loss. Whereas, a cell membrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), is engaged in cell-fusion event required for OC-genesis. This study examined the humoral immune responses to OC-STAMP expressed by human monocytes in relation to anti-Pg antibody.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Blood serum (N=10) collected from systemically healthy human subjects (Precision for Medicine) were measured for IgG antibody titer to Pgor OC-STAMP peptides. Human peripheral blood mononuclear cells were stimulated with MCSF/RANKL with or without anti-OC-STAMP rabbit polyclonal antibody or control rabbit IgG. Affinity purified human anti-OC-STAMP antibody was also tested for its activity to alter the OC-genesis. OC-genesis induced in vitrowas evaluated by TRAP staining and pit formation assay.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>IgG antibody titer to Pgpositively correlated with that to human OC-STAMP peptides (r=0.579, p&lt;0.05). Anti-OC-STAMP auto-antibody purified from human serum with high IgG antibody titer to Pg, as well as anti-OC-STAMP rabbit antibody significantly promoted in vitroOC-genesis (p&lt;0.05).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>The results indicated that Pginfection may be associated with development of anti-OC-STAMP auto-antibody which can promote OC-genesis, suggesting a novel immunological intervention in the pathogenesis of PD.</jats:p> </jats:sec> <jats:sec> <jats:title /> <jats:p>Supported by grants from NIH NIDCR grants, DE-027851, DE-028715 and DE-331851</jats:p> </jats:sec>