{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:18:41Z","timestamp":1790957921457,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T00:00:00Z","timestamp":1642809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Inter\u2010alpha\u2010trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After the enrollment of 93 active RA patients and 50\u00a0health controls (HCs), their serum ITIH4\u00a0level was analyzed by enzyme\u2010linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4\u00a0level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), interleukin (IL)\u20101\u03b2, IL\u20106, and IL\u201017A at baseline of RA patients were also detected by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2\u2013213.5) ng\/mL) than in HCs (306.8 (IQR: 238.9\u2013435.1) ng\/mL) (<jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.001). Furthermore, ITIH4 was negatively related to C\u2010reactive protein (CRP) (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>\u00a0=\u00a0\u22120.358, <jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.001) and 28\u2010joint disease activity score using erythrocyte sedimentation rate (DAS28\u2010ESR) (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>\u00a0=\u00a0\u22120.253, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.014) in RA patients, but not correlated with other clinical features (all <jats:italic>p\u00a0<\/jats:italic>&gt;\u00a00.05). Besides, ITIH4 was negatively linked with TNF\u2010\u03b1 (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>\u00a0=\u00a0\u22120.337, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.001), IL\u20106 (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>\u00a0=\u00a0\u22120.221, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.033), and IL\u201017A (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>\u00a0=\u00a0\u22120.368, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) in RA patients, but not correlated with IL\u20101\u03b2 (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>\u00a0=\u00a0\u22120.195, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Circulating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24231","type":"journal-article","created":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T11:39:18Z","timestamp":1642851558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Inter\u2010alpha\u2010trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk, activity, and treatment outcomes of rheumatoid arthritis"],"prefix":"10.1002","volume":"36","author":[{"given":"Kejian","family":"He","sequence":"first","affiliation":[{"name":"Department of Rheumatology The First College of Clinical Medical Science Three Gorges University &amp; Yichang Central People\u2019s Hospital Yichang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanshan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rheumatism Immunology Minda Hospital of Hubei Minzu University Enshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0356-7657","authenticated-orcid":false,"given":"Min","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The People\u2019s Hospital of China Three Gorges University The First People\u2019s Hospital of Yichang The Institute of Autoimmune Disease of China Three Gorges University Hubei 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