Differences in Salivary Cytokinome and Pathogen Load Between Rheumatoid Arthritis and Other Rheumatic Disease Patients

Rheumatoid arthritis (RA), an autoimmune disease with complex pathogenesis, is characterized by an immune imbalance reflected, e.g., in the disturbed cytokines' profile. Various viruses and bacteria can cause the upregulation of pro-inflammatory cytokines influencing RA development. In particular, oral cavity dysbiosis, observed in multiple chronic diseases including periodontitis, may be linked to RA. The cytokine profile (IL-1β, IP-10, IL-29, GM-CSF, IFN-α2, IFN-β, TGF-β1, MPC-1, TNF-α, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70, IL-2, and IL-4) of RA patients' saliva was evaluated using flow cytometry and benchmarked with their levels in saliva of healthy controls and patients with other rheumatic diseases. The levels of IL-1β, IP-10, IL-2, and IL-4 were significantly elevated in RA patients' saliva compared to other studied groups. To define the potential role of the most suspicious microbial agents (Epstein-Barr Virus (EBV), Cytomegalovirus, Parvovirus B19, <i>Porphyromonas gingivalis</i>, and <i>Segatella copri</i>) for RA pathogenesis, the amounts of their DNA in the saliva of patients with RA were assessed in all the groups mentioned above. The EBV and <i>P. gingivalis</i> DNA levels measured by qRT-PCR were significantly higher in RA patients' saliva than in other groups, indicating either the important role of these agents in RA pathogenesis or the higher susceptibility of RA patients for those infectious factors. The comprehension of the association of specific cytokine profiles in RA and the occurrence of specific viral and/or bacterial infections can be a key to a better understanding of RA pathogenesis. These results illustrate the complexity of the immunological profile of RA, show the high diagnostic potential of saliva, and provide insight into how various infections can contribute to RA development.