{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:11Z","timestamp":1785214751364,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objectives<\/jats:bold>: To investigate the frequency of toll\u2010like receptor 4 (<jats:italic>TLR4<\/jats:italic>) variants c.896A&gt;G (p.Asp299Gly) and c.1196C&gt;T (p.Thr399Ile) among Egyptian children with primary immune thrombocytopenia (pITP), and their association with disease course and response to treatment.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: A case\u2013control study that included 80 children with pITP and 50 age\u2010 and sex\u2010matched healthy controls. <jats:italic>TLR4<\/jats:italic> c.896A&gt;G and c.1196C&gt;T variants were genotyped using polymerase chain reaction\u2013restriction fragment length polymorphism. Patients were classified according to their response to treatment after 3\u00a0months as responders and nonresponders.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: Compared with controls, children with pITP had significantly higher minor allele frequencies of <jats:italic>TLR4<\/jats:italic> p.Asp299Gly (16.25% vs. 6%, odds ratio [OR] 3.04, 95% confidence interval [CI]: 1.16\u20139.36, <jats:italic>p<\/jats:italic> = .014) and p.Thr399Ile (20% vs. 4%, OR 6, 95% CI: 2.02\u201324.01, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). The presence of p.Asp299Gly variant was significantly associated with chronic ITP (OR 7.78, 95% CI: 2.04\u201335.69, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) and non\u2010response to therapy with steroid (OR 11.67, 95% CI: 1.32\u2013104.08, <jats:italic>p<\/jats:italic> = .012), but not thrombopoietin\u2010receptor agonist (OR 1.67, 95% CI: 0.35\u20138.19, <jats:italic>p<\/jats:italic> = .464). Likewise, having p.Thr399Ile variant was significantly associated with chronic ITP (OR 5.14, 95% CI: 1.6\u201317.4, <jats:italic>p<\/jats:italic> = .002) and non\u2010response to therapy with steroid (OR 6.1, 95% CI: 1.01\u201349.06, <jats:italic>p<\/jats:italic> = .046) but not thrombopoietin\u2010receptor agonist (OR 1.57, 95% CI: 0.33\u20137.58, <jats:italic>p<\/jats:italic> = .515).<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>: The presence of <jats:italic>TLR4<\/jats:italic> p.Asp299Gly or p.Thr399Ile variant may be associated with ITP predisposition, chronicity, and non\u2010response to upfront steroid therapy. These findings enhance our understanding of the complex pathophysiology of pITP with potentially important clinical implications.<\/jats:p>","DOI":"10.1002\/pbc.30646","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T13:54:30Z","timestamp":1693230870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Frequency of toll\u2010like receptor 4 variants and association with treatment response in children with primary immune thrombocytopenia"],"prefix":"10.1002","volume":"70","author":[{"given":"Heba A.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Clinical Pathology Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Fahmy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-2989","authenticated-orcid":false,"given":"Elsayed","family":"Abdelkreem","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekram A.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Nafady","sequence":"additional","affiliation":[{"name":"Department of Clinical and Chemical Pathology Faculty of Medicine South Valley University  Qena Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman H.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology South Egypt Cancer Institute Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30173"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000966"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103820"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21616"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29023"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/PROM.S140932"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25716"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000812"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00744"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010013\u20108402\u2010y"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.672346"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/76048"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43807"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2002.128547"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201007\u2010162503"},{"key":"e_1_2_10_17_1","unstructured":"BinkowskiJ MiksS.Gene\u2010Calc\u2014Bioinformatic tool.Gene\u2010Calc;Published2018. 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