{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:23:14Z","timestamp":1793330594938,"version":"4.5.0"},"reference-count":83,"publisher":"American Society of Hematology","issue":"8","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,22]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder associated with autosomal recessive variants in genes required for perforin-mediated lymphocyte cytotoxicity. A rapid diagnosis is crucial for successful treatment. Although defective cytotoxic T lymphocyte (CTL) function causes pathogenesis, quantification of natural killer (NK)\u2013cell exocytosis triggered by K562 target cells currently represents a standard diagnostic procedure for primary HLH. We have prospectively evaluated different lymphocyte exocytosis assays in 213 patients referred for evaluation for suspected HLH and related hyperinflammatory syndromes. A total of 138 patients received a molecular diagnosis consistent with primary HLH. Assessment of Fc receptor\u2013triggered NK-cell and T-cell receptor (TCR)\u2013triggered CTL exocytosis displayed higher sensitivity and improved specificity for the diagnosis of primary HLH than routine K562 cell\u2013based assays, with these assays combined providing a sensitivity of 100% and specificity of 98.3%. By comparison, NK-cell exocytosis after K562 target cell stimulation displayed a higher interindividual variability, in part explained by differences in NK-cell differentiation or large functional reductions after shipment. We thus recommend combined analysis of TCR-triggered CTL and Fc receptor\u2013triggered NK-cell exocytosis for the diagnosis of patients with suspected familial HLH or atypical manifestations of congenital defects in lymphocyte exocytosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024024499","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T13:07:51Z","timestamp":1720012071000},"page":"873-887","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-6117","authenticated-orcid":false,"given":"Samuel C. 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden"},{"name":"5Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"},{"name":"6Division of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-2123","authenticated-orcid":false,"given":"Tessa M.","family":"Campbell","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden"},{"name":"4Division of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, 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