Abstract Background Biological sex influences immune function and inflammatory regulation, but its molecular role in periodontal disease remains insufficiently understood. This pilot study investigated sex-dependent differences in immune gene expression in patients with severe periodontitis. Methods Ten systemically healthy, non-smoking adults (five men and five women) with stage III/IV periodontitis were examined. Total RNA was extracted from saliva and analyzed using the nCounter ® Human Inflammation Panel (NanoString, Bruker Spatial Biology, USA). Results Among 249 immune-related genes analyzed, two showed notable preliminary trends of sex-associated differences: AREG was upregulated in males (log 2 FC = −0.67, d = −1.73, p = 0.03), and NOD2 was elevated in females (log 2 FC = 1.00, d = 1.36, p = 0.03), although these did not remain statistically significant after FDR correction. Conclusion These exploratory results suggest hypothesis-generating trends regarding sex-dependent differences in epithelial repair and innate immunity, highlighting AREG and NOD2 as candidate transcripts for further investigation. These initial findings may serve as a foundation for future, larger-scale multicenter studies with sex-stratified designs integrating transcriptomic, hormonal, and epigenetic analyses to clarify how biological sex influences molecular pathways involved in periodontal inflammation.
Dimitrov et al. (Mon,) studied this question.