{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T15:36:24Z","timestamp":1777217784456,"version":"3.51.4"},"reference-count":66,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,3]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Kaposi sarcoma herpesvirus (KSHV)\u2013associated diseases include Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated multicentric Castleman disease (MCD), and KS inflammatory cytokine syndrome (KICS). PEL, MCD, and KICS are associated with elevated circulating inflammatory cytokines. However, activation of the inflammasome, which generates interleukin-1\u03b2 (IL-1\u03b2) and IL-18 via active caspase-1\/4\/5, has not been evaluated in patients with KSHV-associated diseases (KADs). Herein we report that patients with HIV and \u22651 KAD present with higher plasma levels of IL-18 and increased caspase-1\/4\/5 activity in circulating monocytes compared with HIV-negative healthy volunteers (HVs) or people with HIV (PWH) without KAD. Within KAD subtypes, KICS and MCD shared enhanced caspase-1\/4\/5 activity and IL-18 production compared with HVs and PWH, whereas patients with PEL showed remarkably high levels of inflammasome complex formation (known as apoptosis\u2013associated speck-like protein containing a caspase recruitment domain). Moreover, caspase-1\/4\/5 activity and IL-18 plasma levels correlated with KSHV viral load, indicating KSHV-driven inflammasome activation in KAD. Accordingly, factors released by cells latently infected with KSHV triggered inflammasome activation and cytokine production in bystander monocytes in\u00a0vitro. Finally, both supervised and unsupervised analyses with inflammasome measurements and other inflammatory biomarkers demonstrate a unique inflammatory profile in patients with PEL, MCD, and KICS as compared with KS. Our data indicate that detrimental inflammation in patients with KAD is at least partially driven by KSHV-induced inflammasome activation in monocytes, thus offering novel approaches to diagnose and treat these complex disorders. These trials were registered at www.ClinicalTrials.gov as #NCT01419561, NCT00092222, NCT00006518, and NCT02147405.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024024144","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T20:50:58Z","timestamp":1719607858000},"page":"1496-1507","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Inflammasome activation in patients with Kaposi sarcoma herpesvirus\u2013associated diseases"],"prefix":"10.1182","volume":"144","author":[{"given":"Silvia Lucena","family":"Lage","sequence":"first","affiliation":[{"name":"1HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-4675","authenticated-orcid":false,"given":"Ramya","family":"Ramaswami","sequence":"additional","affiliation":[{"name":"2HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-4934","authenticated-orcid":false,"given":"Joseph M.","family":"Rocco","sequence":"additional","affiliation":[{"name":"1HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Rupert","sequence":"additional","affiliation":[{"name":"3AIDS Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Davis","sequence":"additional","affiliation":[{"name":"2HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-7292","authenticated-orcid":false,"given":"Kathryn","family":"Lurain","sequence":"additional","affiliation":[{"name":"2HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Manion","sequence":"additional","affiliation":[{"name":"1HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 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