Elevated Histamine Receptor 2 and Toll‐Like Receptor 7 Expression in Rheumatoid Arthritis: Insights Into Inflammatory Mechanisms and Potential Therapeutic Strategies
Ahmed Kamil Al‐Basri, Sima Sedighi, Yasser Bagheri, Marieh Saghaiyan Jazi, Emad Heydari, Hossein Azimi, Homa DavoodiABSTRACT
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.