SERUM AND SALIVARY CALPROTECTIN (S100A8/A9) AS A CONVERGENT BIOMARKER ACROSS THE RHEUMATOID ARTHRITIS–PERIODONTITIS AXIS: A PERSPECTIVE FROM PILOT Q-TOF PEPTIDOMIC SCREENING

Abstract

Rheumatoid arthritis (RA) and periodontitis are increasingly recognised as bidirectionally linked inflammatory diseases that converge on shared innate-immune effectors. Calprotectin (S100A8/A9), a neutrophil- and monocyte-derived alarmin, is among the most consistently validated soluble biomarkers of RA disease activity, frequently outperforming C-reactive protein and the erythrocyte sedimentation rate, and it is independently implicated in periodontal tissue inflammation. We revisit this evidence alongside a pilot untargeted Q-TOF peptidomic screen of serum and saliva from Control, RA-without-periodontitis, and RA-with-periodontitis groups. Calprotectin-family peptides were the third most differentially detected signal among sixteen screened protein/peptide families (Fisher's exact p = 3.85 × 10⁻⁴, Cramér's V = 0.75, serum), rising from 0% detection in Control to 77.8% in RA-without-periodontitis (odds ratio 51, 95% CI 2.1–1240.3). Detection was markedly lower in the RA-with-periodontitis subgroup (10%), a non-monotonic pattern we interpret cautiously given the small pilot sample. We present this as a data-anchored perspective, not a validated diagnostic claim: the findings reinforce calprotectin's candidacy as a dual-fluid, treat-to-target biomarker for RA, while surfacing an open question — whether concurrent periodontitis alters detectable calprotectin signal — that merits investigation in adequately powered, quantitatively calibrated cohorts.