{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:28:06Z","timestamp":1790742486966,"version":"4.1.0"},"reference-count":50,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition. Primary HLH occurs early in life as a result of monogenic biallelic mutations affecting lymphocyte cytotoxicity. Secondary HLH occurs mostly in adults secondary to infection, lymphoma, or rheumatic disease. In this latter setting, lymphocyte cytotoxicity status is not known. We conducted a systematic evaluation of natural killer (NK) cell cytotoxicity in adult patients with secondary HLH. Adult patients with secondary HLH were prospectively studied ex vivo for total lymphocyte count and subtype, NK cell phenotype, perforin expression and degranulation, and natural or antibody-dependent cell cytotoxicity, in comparison with patients affected by the same underlying disease without HLH (disease controls [DCs]) and with healthy controls (HCs). Screening for variants of cytotoxity genes was systematically performed. 68 patients were included in the HLH group and 34 each in the DC and HC groups. In HLH patients, severe and transient lymphopenia, activated NK cell phenotype (eg, increased CD69, ICAM-1, HLADR, and CCR5 expression), and decreased capacity of interferon \u03b3 production were observed; mean perforin expression was normal; and degranulation tests and NK cell cytotoxicity were not different from those in DCs. A monoallelic variant of uncertain significance affecting a lymphocyte cytotoxicity gene or the perforin variant A91V was observed in almost 50% of the patients. We detected no major intrinsic cytotoxicity dysfunction in secondary HLH patients compared with DCs and no predicted pathogenic gene variant. The activated NK phenotype profile associated with decreased interferon \u03b3 production seems similar to those of other hyperinflammatory diseases such as sepsis or systemic juvenile idiopathic arthritis.<\/jats:p>","DOI":"10.1182\/blood.2019003664","type":"journal-article","created":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T09:13:56Z","timestamp":1588324436000},"page":"542-552","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":89,"title":["Functional and genetic testing in adults with HLH reveals an inflammatory profile rather than a cytotoxicity defect"],"prefix":"10.1182","volume":"136","author":[{"given":"Julien","family":"Carvelli","sequence":"first","affiliation":[{"name":"Service de M\u00e9decine Interne et Immunologie Clinique, CHU de la Conception, Assistance Publique\u2013H\u00f4pitaux de Marseille (AP-HM), Aix-Marseille Universit\u00e9, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Piperoglou","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunologie, H\u00f4pital de la Timone, AP-HM, Marseille Immunop\u00f4le, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Farnarier","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunologie, H\u00f4pital de la Timone, AP-HM, Marseille Immunop\u00f4le, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-0949","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Vely","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunologie, H\u00f4pital de la Timone, AP-HM, Marseille Immunop\u00f4le, Marseille, France;"},{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Aix-Marseille Universit\u00e9, Centre National de la Recherche Scientifique, INSERM, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Mazodier","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne et Immunologie Clinique, CHU de la Conception, Assistance Publique\u2013H\u00f4pitaux de Marseille (AP-HM), Aix-Marseille Universit\u00e9, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4708-1034","authenticated-orcid":false,"given":"Sandra","family":"Audonnet","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunologie, H\u00f4pital de la Timone, AP-HM, Marseille Immunop\u00f4le, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2094-3298","authenticated-orcid":false,"given":"Patrick","family":"Nitschke","sequence":"additional","affiliation":[{"name":"Plateforme de Bioinformatique, Universit\u00e9 Paris Descartes, Paris, 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