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Further functional effects were tested by small interfering RNA knockdown of the gene for interferon regulatory factor 5 (IRF5), followed by reverse transcription\u2013qPCR (RT\u2010qPCR) and enzyme\u2010linked immunosorbent assay (ELISA) to measure the levels of IFN\u03b3 messenger RNA (mRNA) and protein, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In nuclear extracts from CD8+ T cells, results of qMS showed that relative TF binding to the AS\u2010risk A allele of\n                      <jats:italic>rs4648889<\/jats:italic>\n                      was increased 3.7\u2010fold (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.03) for Ikaros family zinc\u2010finger protein 3 (IKZF3; Aiolos) and components of the NuRD complex, including chromodomain helicase DNA binding protein 4 (CHD4) (3.6\u2010fold increase;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) and retinoblastoma binding protein 4 (RBBP4) (4.1\u2010fold increase;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.03). In contrast, IRF5 bound significantly more to the AS\u2010protective G allele compared to the AS\u2010risk A allele (fold change 8.2;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.003). Validation with Western blotting, EMSA, and ChIP\u2010qPCR confirmed the differential allelic binding of IKZF3, CHD4, RBBP4, and IRF5. Silencing of\n                      <jats:italic>IRF5<\/jats:italic>\n                      in CD8+ T cells increased the levels of IFN\u03b3 mRNA as measured by RT\u2010qPCR (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.03) and IFN\u03b3 protein as measured by ELISA (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.02).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest that the association of\n                      <jats:italic>rs4648889<\/jats:italic>\n                      with AS reflects allele\u2010specific binding of this enhancer\u2010like region to certain TFs, including IRF5, IKZF3, and members of the NuRD complex. IRF5 may have crucial influences on the functions of CD8+ lymphocytes, a finding that could reveal new therapeutic targets for the management of AS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41628","type":"journal-article","created":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T08:49:44Z","timestamp":1608972584000},"page":"980-990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Functional Genomic Analysis of a\n                    <i>RUNX3<\/i>\n                    Polymorphism Associated With Ankylosing Spondylitis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-1316","authenticated-orcid":false,"given":"Matteo","family":"Vecellio","sequence":"first","affiliation":[{"name":"NIHR Oxford Musculoskeletal Biomedical Research Unit Botnar Research Centre Nuffield Orthopaedic Centre NIHR Oxford Comprehensive Biomedical Research Centre University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liye","family":"Chen","sequence":"additional","affiliation":[{"name":"NIHR Oxford Musculoskeletal Biomedical Research Unit Botnar Research Centre Nuffield Orthopaedic Centre NIHR Oxford Comprehensive Biomedical Research Centre University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla J.","family":"Cohen","sequence":"additional","affiliation":[{"name":"NIHR Oxford Musculoskeletal Biomedical Research Unit Botnar Research Centre Nuffield Orthopaedic Centre NIHR Oxford Comprehensive Biomedical Research Centre University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Cortes","sequence":"additional","affiliation":[{"name":"John Radcliffe Hospital Wellcome Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xiamen University and Xiamen University School of Medicine  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bonham","sequence":"additional","affiliation":[{"name":"Target Discovery Institute University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Selmi","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew\u00a0A.","family":"Brown","sequence":"additional","affiliation":[{"name":"NIHR Guy\u2019s and St. Thomas\u2019 Biomedical Research Centre, London, UK, and University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Fischer","sequence":"additional","affiliation":[{"name":"Target Discovery Institute University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian C.","family":"Knight","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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