{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:19:34Z","timestamp":1787570374318,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and joint damage. Toll\u2010like 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\u201010, and TNF\u2010\u03b1 in RA patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2010time PCR (RT\u2010PCR), while plasma levels of histamine, TNF\u2010\u03b1, and IL\u201010 were assessed using ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      H2R and TLR7 gene expression in PBMCs was significantly higher in RA patients than in controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0013,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0057), with newly diagnosed patients showing increased H2R expression compared to treated individuals (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0004). Plasma levels of histamine, TNF\u2010\u03b1, and IL\u201010 were elevated in RA patients, with higher histamine and TNF\u2010\u03b1 levels in newly diagnosed cases and increased IL\u201010 in treated patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0253). Significant correlations were observed between H2R and TLR7 expression (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.68,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and between H2R expression and histamine levels (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70803","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:14:56Z","timestamp":1786443296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Histamine Receptor 2 and Toll\u2010Like Receptor 7 Expression in Rheumatoid Arthritis: Insights Into Inflammatory Mechanisms and Potential Therapeutic Strategies"],"prefix":"10.1111","volume":"29","author":[{"given":"Ahmed","family":"Kamil Al\u2010Basri","sequence":"first","affiliation":[{"name":"Department of Immunology School of Medicine, Golestan University of Medical Sciences  Gorgan 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