Abstract
Purpose
Periodontal disease is considered to be a risk factor for threatened preterm labor (TPL) and preterm birth (PB), but pathogenic mechanisms have not yet been elucidated. We hypothesized that infection with periodontopathic bacteria may enhance thrombosis through molecular mimicry with TLRVYK peptides on beta-2 glycoprotein I, a target molecule in anti-phospholipid syndrome. This study aimed to examine the effects of periodontitis on TPL and PB.
Methods
Ninety-five pregnant women (47 TPL and 48 healthy subjects) participated. Periodontal clinical parameters and periodontopathic bacteria were examined. Molecular mimicry between TLRVYK peptides and homologous peptides on the periodontopathic bacteria was examined by enzyme-linked immunosorbent assay (ELISA) using rabbit polyclonal antibodies specific for the respective peptides (SIRVYK on Aggregatibacter actinomycetemcomitans, TLRIYT on Porphyromonus gingivalis, and TLALYK on Treponema denticola). Serum high-sensitivity C-reactive protein, anti-TLRVYK and anti-SIRVYK IgG antibodies were measured using ELISA.
Results
Among the rabbit antibodies specific for the bacterial homologous peptides, only anti-SIRVYK IgG antibody reacted with TLRVYK peptides. Multivariable analysis showed that anti-SIRVYK IgG antibody was significantly associated with diagnosis of TPL. Of 95 births, 14 (14.7 %) delivered preterm. The preterm birth rate was higher in the anti-SIRVYK IgG antibody >median group than in the ≤median group. Of the 47 TPL subjects 13 had PB, and ordinal logistic regression analysis revealed that past smoking, presence of P. gingivalis and anti-SIRVYK IgG antibody were significantly correlated with PB.
Conclusions
Infection with P. gingivalis and the antibody response to SIRVYK might be associated with TPL and PB.
Similar content being viewed by others
References
World Health Organization (1977) International Classification of Diseases: manual of the international statistical classification of diseases, injuries, and causes of death, ninth revision. World Health Organization, Geneva, Switzerland, pp 307–309
Kirschbaum T (1993) Antibiotics in the treatment of preterm labor. Am J Obstet Gynecol 168:1239–1246
The Canadian Preterm Labor Investigators Group (1992) Treatment of preterm labor with the beta-adrenergic agonist ritodrine. N Engl J Med 327:308–312
Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820
Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS (1997) Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontol 2000 14:216–248
Slade GD, Offenbacher S, Beck JD, Heiss G, Pankow JS (2000) Acute-phase inflammatory response to periodontal disease in the US population. J Dent Res 79:49–57
Wu T, Trevisan M, Genco RJ, Falkner KL, Dorn JP, Sempos CT (2000) Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol 151:273–282
Offenbacher S, Katz V, Fertik G et al (1996) Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol 67:1103–1113
Hasegawa K, Furuichi Y, Shimotsu A et al (2003) Associations between systemic status, periodontal status, serum cytokine levels, and delivery outcomes in pregnant women with a diagnosis of threatened premature labor. J Periodontol 74:1764–1770
Offenbacher S, Lin D, Strauss R et al (2006) Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study. J Periodontol 77:2011–2024
Sert T, Kirzioglu FY, Fentoglu O, Aylak F, Mungan T (2011) Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes. J Periodontol 82:1735–1748
Smadja D, Gaussem P, Roncal C, Fischer AM, Emmerich J, Darnige L (2010) Arterial and venous thrombosis is associated with different angiogenic cytokine patterns in patients with antiphospholipid syndrome. Lupus 19:837–843
Abrahams VM (2009) Mechanisms of antiphospholipid antibody-associated pregnancy complications. Thromb Res 124:521–525
Kandiah DA, Krilis SA (1994) Beta 2-glycoprotein I. Lupus 3:207–212
Bakimer R, Fishman P, Blank M, Sredni B, Djaldetti M, Shoenfeld Y (1992) Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3). J Clin Invest 89:1558–1563
Blank M, Shoenfeld Y, Cabilly S, Heldman Y, Fridkin M, Katchalski-Katzir E (1999) Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides. Proc Natl Acad Sci USA 96:5164–5168
Blank M, Krause I, Fridkin M et al (2002) Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. J Clin Invest 109:797–804
Schenkein HA, Berry CR, Burmeister JA, Brooks CN, Barbour SE, Best AM, Tew JG (2003) Anti-cardiolipin antibodies in sera from patients with periodontitis. J Dent Res 82:919–922
Wang D, Nagasawa T, Chen Y et al (2008) Molecular mimicry of Aggregatibacter actinomycetemcomitans with beta2 glycoprotein I. Oral Microbiol Immunol 23:401–405
Chen YW, Nagasawa T, Wara-Aswapati N et al (2009) Association between periodontitis and anti-cardiolipin antibodies in Buerger disease. J Clin Periodontol 36:830–835
Ashimoto A, Chen C, Bakker I, Slots J (1996) Polymerase chain reaction detection of 8 putative periodontal pathogens in subgingival plaque of gingivitis and advanced periodontitis lesions. Oral Microbiol Immunol 11:266–273
Vergnes JN, Sixou M (2007) Preterm low birth weight and maternal periodontal status: a meta-analysis. Am J Obstet Gynecol 196(135):e1–e7
Wang D, Kawashima Y, Nagasawa T et al (2005) Elevated serum IgG titer and avidity to Actinobacillus actinomycetemcomitans serotype c in Japanese periodontitis patients. Oral Microbiol Immunol 20:172–179
Fine DH, Kaplan JB, Kachlany SC, Schreiner HC (2006) How we got attached to Actinobacillus actinomycetemcomitans: a model for infectious diseases. Periodontol 2000 42:114–157
Pitiphat W, Gillman MW, Joshipura KJ, Williams PL, Douglass CW, Rich-Edwards JW (2005) Plasma C-reactive protein in early pregnancy and preterm delivery. Am J Epidemiol 162:1108–1113
Offenbacher S, Jared HL, O’Reilly PG et al (1998) Potential pathogenic mechanisms of periodontitis associated pregnancy complications. Ann Periodontol 3:233–250
Collins JG, Smith MA, Arnold RR, Offenbacher S (1994) Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster. Infect Immun 62:4652–4655
Arce RM, Barros SP, Wacker B, Peters B, Moss K, Offenbacher S (2009) Increased TLR4 expression in murine placentas after oral infection with periodontal pathogens. Placenta 30:156–162
Katz J, Chegini N, Shiverick KT, Lamont RJ (2009) Localization of P. gingivalis in preterm delivery placenta. J Dent Res 88:575–578
Barak S, Oettinger-Barak O, Machtei EE, Sprecher H, Ohel G (2007) Evidence of periopathogenic microorganisms in placentas of women with preeclampsia. J Periodontol 78:670–676
Leon R, Silva N, Ovalle A et al (2007) Detection of Porphyromonas gingivalis in the amniotic fluid in pregnant women with a diagnosis of threatened premature labor. J Periodontol 78:1249–1255
Johnson GK, Guthmiller JM (2007) The impact of cigarette smoking on periodontal disease and treatment. Periodontol 2000 44:178–194
Ahlborg G Jr, Bodin L (1991) Tobacco smoke exposure and pregnancy outcome among working women. A prospective study at prenatal care centers in Orebro County, Sweden. Am J Epidemiol 133:338–347
Aliyu MH, Lynch O, Saidu R, Alio AP, Marty PJ, Salihu HM (2010) Intrauterine exposure to tobacco and risk of medically indicated and spontaneous preterm birth. Am J Perinatol 27:405–410
Acknowledgments
We are grateful to all the study participants. This study was supported by a Grant-in-Aid for Young Scientists (B) (21792111), and the 8020 Promotion Foundation. The authors declare that there is no conflict of interest associated with this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ye, C., Katagiri, S., Miyasaka, N. et al. The anti-phospholipid antibody-dependent and independent effects of periodontopathic bacteria on threatened preterm labor and preterm birth. Arch Gynecol Obstet 288, 65–72 (2013). https://doi.org/10.1007/s00404-013-2741-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-013-2741-z