# Exploring Persistent Apical Periodontitis in Humans: Integrative Genetic, Histological and Microbiological Perspectives for Translational Research

## TL;DR

This study explores how genetic differences and microbial factors influence persistent apical periodontitis in humans, offering insights into its biological mechanisms.

## Contribution

The study integrates genetic, histological, and microbiological data to explore the role of polymorphisms in persistent apical periodontitis.

## Key findings

- Genetic polymorphisms modulate gene expression and protein activity in persistent apical periodontitis.
- Periapical cysts showed strong positivity for SOCS-1 and IL-1β proteins, unlike granulomas.
- Four bacterial species were identified in persistent periapical infections.

## Abstract

To evaluate the impact of polymorphisms in SOCS‐1, TNF‐α and RANKL on gene expression of RANK, RANKL, TNFRSF1, SOCS‐1, IL‐10, IL‐1β and TNF‐α, and to evaluate the histopathological, immunohistochemical and microbiological aspects of persistent apical periodontitis (PAP) after root canal treatment (RCT) in Brazilian individuals.

Patients with pulp necrosis and apical periodontitis at the time of the non‐surgical RCT (NSRCT) were followed up for at least 1 year after NSRCT. In view of the need for surgical intervention (cases assessed with a CBCTPAI score of 4 and 5, with the presence of symptoms), 20 patients were selected for endodontic surgery, which was planned using cone beam computed tomography images. Initially, saliva was collected as a source of genomic DNA, and the individuals were genotyped for SOCS‐1, TNF‐α and RANKL polymorphisms by real‐time PCR. After collecting the biological material, the periapical lesions obtained were subjected to analysis of gene expression levels for RANK, RANKL, TNFRSF1, SOCS‐1, IL‐10, IL‐1β and TNF‐α, and histopathological evaluation for characterisation and differentiation into periapical granulomas and cysts; immunohistochemical evaluation for SOCS‐1 and IL‐1β protein labeling; and microbiological analysis to identify the microorganisms involved in persistent periapical infection. The relative mRNA expression values of each gene in each group, according with genotypes in different SNPs, were analysed using one‐way analysis of variance followed by Tukey's post‐test or T‐test (α = 5%).

Different expression values of the genes evaluated were observed according to the genotypes of the polymorphisms evaluated in relation to PAP (p < 0.05). Among the cases submitted for histopathological evaluation, 66.7% were diagnosed as periapical granuloma and 33.3% as periapical cyst. Immunohistochemical analysis showed strong positivity for SOCS‐1 and IL‐1β in the lesions classified as periapical cyst, while the lesions diagnosed as periapical granuloma were not labelled. In the microbiological analysis, four different species of bacteria were isolated:
Pseudomonas aeruginosa
,
Staphylococcus epidermidis
,
Enterococcus faecalis
and
Bacillus cereus
.

This exploratory study indicates that genetic polymorphisms can modulate gene expression and protein activity in PAP, shaping the host's inflammatory and reparative response. These findings highlight their potential as biomarkers and establish a basis for future translational studies.