SALIVARY HISTATIN-1 AS A NON-INVASIVE SENTINEL OF ORAL–SYSTEMIC DYSREGULATION IN RHEUMATOID ARTHRITIS: A PERSPECTIVE FROM PILOT Q-TOF PEPTIDOMIC SCREENING

Abstract

Histatin-1 is a histidine-rich antimicrobial peptide secreted almost exclusively by the salivary glands, where it also drives oral wound healing and angiogenesis — functions of particular interest in rheumatoid arthritis (RA), an autoimmune disease independently associated with delayed wound healing. We examine histatin-1's candidacy as a non-invasive, saliva-accessible marker of the RA–periodontitis axis using a pilot untargeted Q-TOF peptidomic screen of serum and saliva across Control, RA-without-periodontitis, and RA-with-periodontitis groups. Among sixteen candidate protein/peptide families screened, histatin-1 was the second most differentially detected signal in serum (Fisher's exact p = 4.95 × 10⁻⁵, Cramér's V = 0.84), rising from 0% detection in Control to 77.8% in RA-without-periodontitis (odds ratio 51, 95% CI 2.1–1240.3) before falling back to 0% in RA-with periodontitis — the same non-monotonic pattern observed for two companion markers screened from the same dataset. In saliva, by contrast, histatin-1 was detected in every Control sample (2/2) and in most RA samples, a markedly different shape from its serum profile. We use these pilot findings to motivate, rather than conclude, a case for treating saliva as a legitimate primary sampling matrix in RA biomarker discovery, and we detail specifically why the present dataset falls short of that standard on its own.