{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:03:14Z","timestamp":1790877794628,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T00:00:00Z","timestamp":1482883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fund for Scientific Research, Flanders","award":["G.0515.12N and G.OD66.13"],"award-info":[{"award-number":["G.0515.12N and G.OD66.13"]}]},{"name":"Regional Government of Flanders","award":["GOA13\/014"],"award-info":[{"award-number":["GOA13\/014"]}]},{"name":"Interuniversity Attraction Poles","award":["IAP P7\/39"],"award-info":[{"award-number":["IAP P7\/39"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory disease characterized by arthritis and systemic manifestations. The role of natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear. The purpose of this study was to perform a comprehensive analysis of NK cell phenotype and functionality in patients with systemic JIA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptional alterations specific to NK cells were investigated by RNA sequencing of highly purified NK cells from 6 patients with active systemic JIA and 6 age\u2010matched healthy controls. Cytokines (NK cell\u2013stimulating and others) were quantified in plasma samples (n\u2009=\u200918). NK cell phenotype and cytotoxic activity against tumor cells were determined (n\u2009=\u200910), together with their interferon\u2010\u03b3 (IFN\u03b3)\u2013producing function (n\u2009=\u20098).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NK cells from the systemic JIA patients showed an altered gene expression profile compared to cells from the healthy controls, with enrichment of immunoinflammatory pathways, increased expression of innate genes including\n                      <jats:italic>TLR4<\/jats:italic>\n                      and\n                      <jats:italic>S100A9<\/jats:italic>\n                      , and decreased expression of immune\u2010regulating genes such as\n                      <jats:italic>IL10RA<\/jats:italic>\n                      and\n                      <jats:italic>GZMK<\/jats:italic>\n                      . In the patients\u2019 plasma, interleukin\u201018 (IL\u201018) levels were increased, and a decreased ratio of IFN\u03b3 to IL\u201018 was observed. NK cells from the patients exhibited specific alterations in the balance of inhibitory and activating receptors, with decreased killer cell lectin\u2010like receptor G1 and increased NKp44 expression. Although NK cells from the patients showed increased granzyme B expression, consistent with intact cytotoxicity and degranulation against a tumor cell line, decreased granzyme K expression in CD56\n                      <jats:sup>bright<\/jats:sup>\n                      NK cells and defective IL\u201018\u2013induced IFN\u03b3 production and signaling were demonstrated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NK cells are active players in the inflammatory environment typical of systemic JIA. Although their cytotoxic function is globally intact, subtle defects in NK\u2010related pathways, such as granzyme K expression and IL\u201018\u2013driven IFN\u03b3 production, may contribute to the immunoinflammatory dysregulation in this disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39933","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T08:57:53Z","timestamp":1475830673000},"page":"213-224","source":"Crossref","is-referenced-by-count":82,"title":["Inflammatory Gene Expression Profile and Defective Interferon\u2010\u03b3 and Granzyme K in Natural Killer Cells From Systemic Juvenile Idiopathic Arthritis Patients"],"prefix":"10.1002","volume":"69","author":[{"given":"Karen","family":"Put","sequence":"first","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-8806","authenticated-orcid":false,"given":"Jessica","family":"Vandenhaute","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneleen","family":"Avau","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8576-7523","authenticated-orcid":false,"given":"Annemarie","family":"van Nieuwenhuijze","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Brisse","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Dierckx","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Rutgeerts","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josselyn E.","family":"Garcia\u2010Perez","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaan","family":"Toelen","sequence":"additional","affiliation":[{"name":"University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Waer","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Leclercq","sequence":"additional","affiliation":[{"name":"Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Goris","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Van Weyenbergh","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Liston","sequence":"additional","affiliation":[{"name":"University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"De Somer","sequence":"additional","affiliation":[{"name":"University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine 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