Potential of salivary biomarkers for diagnosing and prognosing rheumatoid arthritis: A systematic review and meta-analysis: Salivary biomarkers in Rheumatoid Arthritis patients – A systematic review with Meta-analysis

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder. Blood biomarkers, like rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), lack the sensitivity and specificity for early diagnosis, delaying treatment. This review while highlighting the need for new diagnostic tools, emphasizes the promising avenue of saliva for developing RA biomarkers. This systematic review and meta-analysis assess the effectiveness of salivary biomarkers in the diagnosis and prognosis of RA, examining current evidence and proposing avenues for future research. A literature review following PRISMA 2021 guidelines was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies from the past five years on salivary biomarkers in RA patients compared to healthy controls. The review focused on original research articles, and meta-analysis was performed on studies reporting standard deviation values for inflammatory markers such as IL-6, IL-8, MMP-8, and TNF-alpha. The meta-analysis included eleven studies with 394 RA patients and 255 healthy controls, evaluating IL-8, IL-6, MMP-8, and TNF-α as RA biomarkers. IL-8 showed a mean difference of 7.32 (CI: -5.48 to 20.13), not statistically significant, favouring controls. IL-6 had a CI of -0.09 (CI: -2.20 to 2.02) with high heterogeneity (I² = 98%), suggesting its potential as a diagnostic and prognostic biomarker. TNF-α and MMP-8 showed no significant differences (CIs: 4.54 and 2.71, respectively). This systematic review and meta-analysis emphasize saliva's potential in identifying RA biomarkers, especially IL-6, which is associated with the disease's pathogenesis. However, significant evidence heterogeneity necessitates larger, multicentric studies for validation