Elevated Histamine Receptor 2 and Toll-Like Receptor 7 Expression in Rheumatoid Arthritis: Insights Into Inflammatory Mechanisms and Potential Therapeutic Strategies.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and joint damage. Toll-like receptor 7 (TLR7), one of the innate immunity receptors, plays a role in releasing inflammatory mediators like cytokines and histamine. These mediators are crucial in inducing and maintaining chronic inflammation in the joints. This study examines the relationship between histamine receptor 2 (H2R) and TLR7 expression in peripheral blood mononuclear cells (PBMCs) and evaluates plasma levels of histamine, IL-10, and TNF-α in RA patients. METHODS: The study included 60 RA patients (22 newly diagnosed and 38 undergoing treatment) and 30 healthy controls. H2R and TLR7 gene expression in PBMCs was measured using Real-time PCR (RT-PCR), while plasma levels of histamine, TNF-α, and IL-10 were assessed using ELISA. RESULTS: H2R and TLR7 gene expression in PBMCs was significantly higher in RA patients than in controls (p = 0.0013, p = 0.0057), with newly diagnosed patients showing increased H2R expression compared to treated individuals (p = 0.0004). Plasma levels of histamine, TNF-α, and IL-10 were elevated in RA patients, with higher histamine and TNF-α levels in newly diagnosed cases and increased IL-10 in treated patients (p = 0.0253). Significant correlations were observed between H2R and TLR7 expression (R = 0.68, p < 0.0001) and between H2R expression and histamine levels (R = 0.34, p = 0.01). CONCLUSIONS: Our study suggests a potential link between H2R signaling and TLR7 activation in RA. The therapeutic potential of H2R inhibitors and TLR7 antagonists in mitigating RA progression warrants further investigation.