title: Serum antibodies to Porphyromonas gingivalis chaperone HtpG predict health in periodontitis susceptible patients.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biologic and Materials Sciences, The University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America. ceshelbu@umich.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Shelburne
authors.forename: P Sandra
authors.initials: PS
authors.lastname: Shelburne
authors.forename: Vishnu M
authors.initials: VM
authors.lastname: Dhople
authors.forename: Domenica G
authors.initials: DG
authors.lastname: Sweier
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
authors.forename: Janet S
authors.initials: JS
authors.lastname: Kinney
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Coulter
authors.forename: Brian H
authors.initials: BH
authors.lastname: Mullally
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Lopatin
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D016000:Cluster Analysis; D015169:Colony Count, Microbial; D003773:Dental Plaque / Q000382:microbiology; D004198:Disease Susceptibility; D005260:Female; D016967:Fusobacterium nucleatum / Q000254:growth & development / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology*; D006262:Health; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D018832:Molecular Chaperones / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000254:growth & development / Q000276:immunology*; D044967:Serum
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018841:HSP90 Heat-Shock Proteins; D007074:Immunoglobulin G; D018832:Molecular Chaperones; D010455:Peptides; C066720:HtpG protein, bacteria