A large case-control study has identified distinct serum protein profiles in patients with severe periodontitis, potentially revealing new biomarkers and insights into the disease's systemic effects.
In the PerioGene North study, published in the Journal of Dental Research, researchers analyzed the serum levels of 45 inflammation-related proteins and high-sensitivity C-reactive protein (hs-CRP) in 478 patients with severe periodontitis and 509 periodontally healthy controls.
The study used comprehensive oral examinations and serum sample analysis. The participants were recruited between 2007 and 2019 from specialist clinics and general dental care in northern Sweden. Cases had at least one tooth in each quadrant with alveolar bone loss ≥ 1/3 of the root length and ≥ 15 remaining teeth. Controls had no alveolar bone loss, probing depths < 4 mm, ≥ 24 remaining teeth, and were ≥ 34 years old.
Among the key findings were:
- Twenty-four of the 45 analyzed proteins and hs-CRP showed significantly different levels between periodontitis cases and controls after adjusting for confounders.
- High levels of hs-CRP and matrix metalloproteinase-12 (MMP-12) were strongly associated with periodontitis. The median hs-CRP level was 3.2 mg/L in cases versus 1.7 mg/L in controls. MMP-12 levels were 1.27 times higher in cases compared with controls.
- Low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were markedly associated with periodontitis. Cases had 3.85 times lower levels of EGF and 1.67 times lower levels of OLR-1 compared with controls.
- Specific proteins were linked to gingival inflammation and pocket probing depth among periodontitis cases. Higher levels of hs-CRP, CCL-19, CSF-3, and IL-7 were associated with high gingival inflammation, whereas CSF-3 and TNFSF-10 levels were higher in cases with a high degree of periodontal pocket depth.
The overall protein profile distinguished cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve [AUC] = 0.87). Individual proteins showed varying discriminatory potential:
- Hs-CRP: sensitivity = 0.74, specificity = 0.52 (AUC = 0.66)
- EGF: sensitivity = 0.78, specificity = 0.75 (AUC = 0.77)
- MMP-12: sensitivity = 0.74, specificity = 0.70 (AUC = 0.77)
- OLR-1: sensitivity = 0.77, specificity = 0.60 (AUC = 0.71).
The researchers also found that periodontitis cases were more frequently ever-smokers, had a lower education level, and more frequently reported heredity for periodontitis.
A limitation of the study was the lack of age-matching between cases and controls, which may have influenced the inability to show associations between periodontitis and related comorbidities after adjusting for confounders.
The researchers noted that the findings of lower EGF and OLR-1 levels among periodontitis cases are novel and should be further investigated. They suggested that these proteins, along with MMP-12, should be validated in additional cohorts for their potential to serve as biomarkers for severe periodontitis. Further, their possible mechanistic role in periodontal inflammation, tissue breakdown, and healing could be new targets for treatment.
The study provided new information on inflammatory-related serum proteins in patients with periodontitis and highlighted the systemic impact of the disease. However, the researchers emphasized the need for further validation and experimental studies to fully understand the significance of these findings.
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.