Salivary Neuropeptide Y, Interleukin-18, Tight Junction Proteins and Malondialdehyde as a Neuroimmune-Barrier Panel in Periodontitis
TL;DR
Salivary neuropeptide Y, interleukin-18 and malondialdehyde are independently associated with periodontitis, whereas salivary tight junction proteins track disease severity without independent association, consistent with downstream barrier injury.
Abstract
Periodontitis involves interacting neural, immune, oxidative and epithelial barrier pathways, yet these are rarely measured together in the same patients. This cross-sectional case–control study evaluated a salivary panel comprising neuropeptide Y, interleukin-18, zonula occludens-1, claudin-2 and malondialdehyde in periodontitis. Forty non-smoking patients with periodontitis (Stage II, n = 20; Stage III–IV, n = 20) and 40 age- and sex-matched periodontitis-free controls were recruited at Tikrit Teaching Hospital, Iraq, between February and July 2026. Unstimulated whole saliva was analyzed by enzyme-linked immunosorbent assay, and diagnostic performance was assessed by receiver operating characteristic analysis with bootstrap internal validation, followed by multivariable logistic regression. All five biomarkers were 1.7- to 2.0-fold higher in periodontitis (all P < 0.001), remained higher after accounting for salivary flow (P ≤ 0.002), increased with disease severity (P for trend < 0.001) and correlated with probing depth, attachment loss and bleeding on probing (Spearman coefficients 0.36–0.52). Individual areas under the curve ranged from 0.74 for claudin-2 to 0.81 for interleukin-18. The combined panel reached an area under the curve of 0.90 (95% confidence interval 0.83–0.97; optimism-corrected 0.88), exceeding interleukin-18 (P = 0.012) and malondialdehyde (P = 0.006). After adjustment for age, sex and plaque index, neuropeptide Y, interleukin-18 and malondialdehyde remained independently associated with periodontitis, whereas zonula occludens-1 and claudin-2 did not. A reduced panel of neuropeptide Y, interleukin-18 and malondialdehyde performed comparably to the full panel (area under the curve 0.88; P = 0.284). Salivary neuropeptide Y, interleukin-18 and malondialdehyde are independently associated with periodontitis, whereas salivary tight junction proteins track disease severity without independent association, consistent with downstream barrier injury.
