Serum Antibodies to Porphyromonas gingivalis Chaperone HtpG Predict Health in Periodontitis Susceptible Patients

Department of Biologic and Materials Sciences, The University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(4):e1984. DOI: 10.1371/journal.pone.0001984
Source: PubMed


Chaperones 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.
ELISA 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.
OUR 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.

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    • "These include lipopolysaccharide (Bainbridge et al., 1997) and a 40-kDa outer membrane antigen (Momoi et al., 2008). Antibody responses to 43-kDa fimbrial protein, Pga30 (30-kDa antigenic protein), PrtC (38-kDa collagenase), and HtpG (heat-shock protein 90 homologue) have also been reported (Condorelli et al., 1998; Hendtlass et al., 2000; Beikler et al., 2003; Shelburne et al., 2008). It is therefore plausible that antibodies to these proteins are involved in case 14. "
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    04/2014; 29(4). DOI:10.1111/mom.12052
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    • "Subgingival plaque biofilm was collected from the mesiobuccal aspect of all teeth at baseline, 6, and 12 mos as described previously (Shelburne et al., 2008). The detection of Porphyromonas gingivalis , Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum, Treponema denticola, and Campylobacter rectus was quantified by qPCR as described previously (Mullally et al., 2000). "
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    Journal of dental research 03/2011; 90(6):752-8. DOI:10.1177/0022034511399908 · 4.14 Impact Factor
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    • "Indeed, the classic periodontopathogens present a series of virulence factors that interfere with the protective responses of phagocytes (Venketaraman et al., 2008; Wang and Hajishengallis, 2008). Besides cellular immunity mechanisms, the humoral immunity axis involving Th2 and B-cells is also thought to contribute to host protection against periodontal pathogens (Shelburne et al., 2008). Also, antibodies produced in response to periodontal infection increase periodontopathogen phagocytosis by opsonization , and consequently enhance the phagocytes' bactericidal activities (Guentsch et al., 2009). "
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    ABSTRACT: Periodontal diseases (PD) are chronic infectious inflammatory diseases characterized by the destruction of tooth-supporting structures, being the presence of periodontopathogens required, but not sufficient, for disease development. As a general rule, host inflammatory mediators have been associated with tissue destruction, while anti-inflammatory mediators counteract and attenuate disease progression. With the discovery of several T-cell subsets bearing distinct immunoregulatory properties, this pro- vs. anti-inflammatory scenario became more complex, and a series of studies has hypothesized protective or destructive roles for Th1, Th2, Th17, and Treg subpopulations of polarized lymphocytes. Interestingly, the "protective vs. destructive" archetype is usually considered in a framework related to tissue destruction and disease progression. However, it is important to remember that periodontal diseases are infectious inflammatory conditions, and recent studies have demonstrated that cytokines (TNF-α and IFN-γ) considered harmful in the context of tissue destruction play important roles in the control of periodontal infection. Therefore, in this review, the state-of-the-art knowledge concerning the protective and destructive roles of host inflammatory immune response will be critically evaluated and discussed from the tissue destruction and control-of-infection viewpoints.
    Journal of dental research 12/2010; 89(12):1349-63. DOI:10.1177/0022034510376402 · 4.14 Impact Factor
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