Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms

Joona Hallikainen; Mikko Pyysalo; Sara Keränen; Jari Kellokoski; Timo Koivisto; Anna Liisa Suominen; Pirkko Pussinen; Tanja Pessi; Juhana Frösen

doi:10.1111/ene.14986

Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms

Eur J Neurol. 2021 Sep;28(9):3089-3099. doi: 10.1111/ene.14986. Epub 2021 Jul 8.

Authors

Joona Hallikainen^{1

2

3}, Mikko Pyysalo³, Sara Keränen^{3

4}, Jari Kellokoski^{1

2}, Timo Koivisto⁵, Anna Liisa Suominen^{1

2

6}, Pirkko Pussinen⁷, Tanja Pessi³, Juhana Frösen^{3

8}

Affiliations

¹ Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.
² Department of Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland.
³ Hemorrhagic Brain Pathology Research Group, University of Tampere, Tampere, Finland.
⁴ A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
⁵ Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
⁶ Finnish Institute for Health and Welfare, Helsinki, Finland.
⁷ Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Department of Neurosurgery, Tampere University Hospital, Tampere, Finland.

PMID: 34145948
DOI: 10.1111/ene.14986

Abstract

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.

Keywords: aneurysms; infections; oral disease; periodontitis; subarachnoid hemorrhage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aggregatibacter actinomycetemcomitans*
Antibodies, Bacterial
Cross-Sectional Studies
Humans
Immunity
Intracranial Aneurysm*
Porphyromonas gingivalis

Substances

Antibodies, Bacterial