Abstract
BackgroundChaperones are ubiquitous conserved proteins critical in stabilization of new proteins, repair/removal of defective proteins and immunodominant antigens in innate and adaptive immunity. Periodontal disease is a chronic inflammatory infection associated with infection by Porphyromonas gingivalis that culminates in the destruction of the supporting structures of the teeth. We previously reported studies of serum antibodies reactive with the human chaperone Hsp90 in gingivitis, a reversible form of gingival disease confined to the oral soft tissues. In those studies, antibodies were at their highest levels in subjects with the best oral health. We hypothesized that antibodies to the HSP90 homologue of P. gingivalis (HtpG) might be associated with protection/resistance against destructive periodontitis.Methodology/Principal FindingsELISA assays using cloned HtpG and peptide antigens confirmed gingivitis subjects colonized with P. gingivalis had higher serum levels of anti-HtpG and, concomitantly, lower levels of attachment loss. Additionally, serum antibody levels to P. gingivalis HtpG protein were higher in healthy subjects compared to patients with either chronic or aggressive periodontitis. We found a negative association between tooth attachment loss and anti-P. gingivalis HtpG (p = 0.043) but not anti-Fusobacterium nucleatum (an oral opportunistic commensal) HtpG levels. Furthermore, response to periodontal therapy was more successful in subjects having higher levels of anti-P. gingivalis HtpG before treatment (p = 0.018). There was no similar relationship to anti-F. nucleatum HtpG levels. Similar results were obtained when these experiments were repeated with a synthetic peptide of a region of P. gingivalis HtpG.Conclusions/SignificanceOur results suggest: 1) anti-P. gingivalis HtpG antibodies are protective and therefore predict health periodontitis-susceptable patients; 2) may augment the host defence to periodontitis and 3) a unique peptide of P. gingivalis HtpG offers significant potential as an effective diagnostic target and vaccine candidate. These results are compatible with a novel immune control mechanism unrelated to direct binding of bacteria.
Highlights
Porphyromonas gingivalis is a gram negative obligate anaerobe that has a major etiological role in human periodontitis
We have recently described experiments that indicate that antibodies to HtpG may mitigate some of the induction of inflammatory chemokines through TLR4 and CD91 [12], a receptor expressed in human atherosclerotic lesions [13]. These findings suggest a role for antibodies to P. gingivalis chaperones in both periodontal and cardiovascular disease
Colonization of plaque by P. gingivalis and F. nucleatum Initially we reported [9] that in gingivitis subjects probing depth and the levels of P. gingivalis were both associated with serum antiHsp90 antibody levels
Summary
Porphyromonas gingivalis is a gram negative obligate anaerobe that has a major etiological role in human periodontitis. The bacterium is found with high frequency in persons with periodontitis where it participates in the initiation and establishment of chronic, infectious biofilms [1,2] These biofilms facilitate the long term survival of P. gingivalis and induces an inflammatory reaction that is responsible for the destruction of the hard and soft tissue supporting structures of the teeth. HtpG, like most chaperones tested [8], induces a strong humoral response that may have consequences in the pathogenesis of periodontitis [9] These functions are important in the establishment and perpetuation of chronic inflammatory diseases. We previously reported studies of serum antibodies reactive with the human chaperone Hsp in gingivitis, a reversible form of gingival disease confined to the oral soft tissues. We hypothesized that antibodies to the HSP90 homologue of P. gingivalis (HtpG) might be associated with protection/resistance against destructive periodontitis
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