Introduction: Autoimmune (AI) – rheumatological diseases represent a tangled display of illnesses characterized by autoreactivity of T – B lymphocytes, with a great mortality and morbidity rate to general population. Rheumatoid Arthritis (RA), a disease characterized by synovial inflammation with a plethora of articular and extra-articular manifestations, is among the most common of them. Serum and other biological fluids analysis are used traditionally for the diagnosis of these diseases. However, an increasing number of studies propose saliva as an alternative. Aim of this study is to identify and propose saliva biomarkers (proteins, cytokines, hormone levels, etc.) as a possible diagnostic and follow-up tool for patients with Rheumatoid Arthritis. Materials and Methods: We carried out a systematic review of the available literature investigating the relationship between Autoimmune Diseases- Rheumatoid Arthritis and salivary biomarkers. Through comprehensive research of three databases (PubMed, Scopus, Cochrane) from 2004 to 2025, eligible studies were identified and selected according to predefined inclusion-exclusion criteria. Quality of the included articles was assessed using the NIH quality assessment tool for Observational Cohort and Cross-Sectional studies and the NIH quality assessment tool for Case-Control Studies. Results: Our research yielded 887 articles among all three databases. Following duplicate removal, from the 793 remaining articles 718 were excluded. Finally, after full text analysis, 60 were included in our systematic review including cross-sectional, case-control and cohort studies. 10 studies reported salivary biomarkers associated with Rheumatoid Arthritis. Salivary proteins were the most frequent biomarkers identified. There was great heterogeneity among methods and protocols used in the different studies. Conclusion: Saliva is a very potent biological fluid and could serve as a valuable clinical asset in the diagnosis and follow up of patients with Rheumatoid Arthritis. However, more well-conducted molecular studies are needed in order to identify novel salivary biiomarkers and to establish standardized protocols.
Fourkiotis et al. (2025) studied this question.