{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:12:21Z","timestamp":1792131141253,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["[NMRC]\/OFYIRG17may066"],"award-info":[{"award-number":["[NMRC]\/OFYIRG17may066"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/OFIRG\/0049\/2017"],"award-info":[{"award-number":["NMRC\/OFIRG\/0049\/2017"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["100562\/Z\/12\/Z"],"award-info":[{"award-number":["100562\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Severe dengue, characterized by shock and organ dysfunction, is driven by an excessive host immune response. We investigated the role of hyperinflammation in dengue pathogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients recruited into an observational study were divided into 3 plasma leak severity grades. Hyperinflammatory biomarkers were measured at 4 time points. Frequencies, activation, and cytotoxic potential of natural killer (NK) cells were analyzed by flow cytometry. RNA was extracted from sorted CD56+ NK cells and libraries were prepared using SMART-Seq and sequenced using HiSeq3000 (Illumina).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sixty-nine patients were included (grade 0, 42 patients; grade 1, 19 patients; grade 2, 8 patients). Patients with grade 2 leakage had higher biomarkers than grade 0, including higher peak ferritin levels (83.3% vs 45.2%) and H-scores (median, 148.5 vs 105.5). NK cells from grade 2 patients exhibited decreased expression of perforin and granzyme B and activation markers. RNA sequencing revealed 3 single-nucleotide polymorphisms in NK cell functional genes associated with more severe leakage\u2014NK cell lectin-like receptor K1 gene (KLRK1) and perforin 1 (PRF1).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Features of hyperinflammation are associated with dengue severity, including higher biomarkers, impaired NK cell function, and polymorphisms in NK cell cytolytic function genes (KLRK1 and PRF1). Trials of immunomodulatory therapy in these patients is now warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiac093","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T12:08:14Z","timestamp":1646741294000},"page":"1338-1347","source":"Crossref","is-referenced-by-count":22,"title":["Hyperinflammatory Syndrome, Natural Killer Cell Function, and Genetic Polymorphisms in the Pathogenesis of Severe Dengue"],"prefix":"10.1093","volume":"226","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2684-3041","authenticated-orcid":false,"given":"Nguyen Lam","family":"Vuong","sequence":"first","affiliation":[{"name":"Oxford University Clinical Research Unit , Ho Chi Minh City , Vietnam"},{"name":"University of Medicine and Pharmacy at Ho Chi Minh City , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Wai","family":"Cheung","sequence":"additional","affiliation":[{"name":"Duke\u2013National 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Hamis","sequence":"additional","affiliation":[{"name":"Duke\u2013National University of Singapore Medical School , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Gregorova","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-1544","authenticated-orcid":false,"given":"Eng Eong","family":"Ooi","sequence":"additional","affiliation":[{"name":"Duke\u2013National University of Singapore Medical School , Singapore"},{"name":"Saw Swee Hock School of Public Health, National University of Singapore , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"October","family":"Sessions","sequence":"additional","affiliation":[{"name":"Duke\u2013National University of Singapore Medical School , Singapore"},{"name":"Saw Swee Hock School of Public 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