TY - JOUR
T1 - Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms
AU - Hallikainen, Joona
AU - Pyysalo, Mikko
AU - Keränen, Sara
AU - Kellokoski, Jari
AU - Koivisto, Timo
AU - Suominen, Anna Liisa
AU - Pussinen, Pirkko
AU - Pessi, Tanja
AU - Frösen, Juhana
N1 - Funding Information:
This study was funded by a research grant from the Finnish Medical Foundation (J.F.) and by a research grant from the Finnish Dental Society Apollonia (J.H.). Kuopio University Hospital Research Grants (VTR) to Dr. Frösen.
Publisher Copyright:
© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology
PY - 2021
Y1 - 2021
N2 - Background and purpose: Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Methods: Immunoglobulin A (IgA) and IgG antibodies against P. gingivalis and A. actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross-sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria-derived epitopes in the IA wall. Results: Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P. gingivalis and A. actinomycetemcomitans were 1.5× and 3–3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p ≤ 0.003). IgG antibodies against P. gingivalis were 1.8× lower in unruptured IA patients (p < 0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P. gingivalis (odds ratio [OR] = 1.4, 95% confidence interval [Cl] = 1.1–1.8 and OR = 1.5, 95% Cl = 1.1–1.9; OR = 0.6, 95% Cl = 0.4–0.7 and OR = 0.5, 95% Cl = 0.4–0.7) and against A. actinomycetemcomitans (OR = 2.3, 95% Cl = 1.7–3.1 and OR = 2.1, 95% Cl = 1.5–2.9; OR = 0.6, 95% Cl = 0.4–0.8 and OR = 0.6, 95% Cl = 0.5–0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P. gingivalis epitopes in the IA wall. Conclusions: Exposure to the periodontal pathogens P. gingivalis and A. actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.
AB - Background and purpose: Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Methods: Immunoglobulin A (IgA) and IgG antibodies against P. gingivalis and A. actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross-sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria-derived epitopes in the IA wall. Results: Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P. gingivalis and A. actinomycetemcomitans were 1.5× and 3–3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p ≤ 0.003). IgG antibodies against P. gingivalis were 1.8× lower in unruptured IA patients (p < 0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P. gingivalis (odds ratio [OR] = 1.4, 95% confidence interval [Cl] = 1.1–1.8 and OR = 1.5, 95% Cl = 1.1–1.9; OR = 0.6, 95% Cl = 0.4–0.7 and OR = 0.5, 95% Cl = 0.4–0.7) and against A. actinomycetemcomitans (OR = 2.3, 95% Cl = 1.7–3.1 and OR = 2.1, 95% Cl = 1.5–2.9; OR = 0.6, 95% Cl = 0.4–0.8 and OR = 0.6, 95% Cl = 0.5–0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P. gingivalis epitopes in the IA wall. Conclusions: Exposure to the periodontal pathogens P. gingivalis and A. actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.
KW - aneurysms
KW - infections
KW - oral disease
KW - periodontitis
KW - subarachnoid hemorrhage
U2 - 10.1111/ene.14986
DO - 10.1111/ene.14986
M3 - Article
C2 - 34145948
AN - SCOPUS:85109388942
SN - 1351-5101
VL - 28
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 9
ER -