{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:35:28Z","timestamp":1775885728138,"version":"3.50.1"},"reference-count":18,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:p>Mutations in the perforin gene have been described in some patients with hemophagocytic lymphohistiocytosis (HLH), but the role of perforin defects in the pathogenesis of HLH remains unclear. Four-color flow cytometric analysis was used to establish normal patterns of perforin expression for control subjects of all ages, and patterns of perforin staining in cytotoxic lymphocytes (natural killer [NK] cells, CD8+ T cells, CD56+ T cells) from patients with HLH and their family members were studied. Eleven unrelated HLH patients and 19 family members were analyzed prospectively. Four of the 7 patients with primary HLH showed lack of intracellular perforin in all cytotoxic cell types. All 4 patients showed mutations in the perforin gene. Their parents, obligate carriers of perforin mutations, had abnormal perforin-staining patterns. Analysis of cytotoxic cells from the other 3 patients with primary HLH and remaining family members had normal percentages of perforin-positive cytotoxic cells. On the other hand, the 4 patients with Epstein-Barr virus\u2013associated HLH typically had depressed numbers of NK cells but markedly increased proportions of CD8+ T cells with perforin expression. Four-color flow cytometry provides diagnostic information that, in conjunction with evidence of reduced NK function, may speed the identification of life-threatening HLH in some families and direct further genetic studies of the syndrome.<\/jats:p>","DOI":"10.1182\/blood.v99.1.61","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T08:46:40Z","timestamp":1027759600000},"page":"61-66","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":204,"title":["Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members"],"prefix":"10.1182","volume":"99","author":[{"given":"Kazuhiro","family":"Kogawa","sequence":"first","affiliation":[{"name":"From the Division of Hematology\/Oncology, Children's Hospital Medical Center, Cincinnati, OH; the Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan; and the Department of Pathology, University of Nebraska, Omaha."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Children's Hospital Medical Center, Cincinnati, OH; the Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan; and the Department of Pathology, University of Nebraska, Omaha."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Villanueva","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Children's Hospital Medical Center, Cincinnati, OH; the Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan; and the Department of Pathology, University of Nebraska, Omaha."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Marmer","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Children's Hospital Medical Center, Cincinnati, OH; the Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan; and the Department of Pathology, University of Nebraska, Omaha."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janos","family":"Sumegi","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Children's Hospital Medical Center, Cincinnati, OH; the Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan; and the Department of Pathology, University of Nebraska, Omaha."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra H.","family":"Filipovich","sequence":"additional","affiliation":[{"name":"From the Division of Hematology\/Oncology, Children's Hospital Medical Center, Cincinnati, OH; the Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan; and the Department of Pathology, University of Nebraska, Omaha."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021219105006600_B1","first-page":"34","article-title":"Familial erythrophagocytic lymphohistiocytosis.","volume":"18","author":"Loy","year":"1991","journal-title":"Semin Oncol."},{"key":"2020021219105006600_B2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/(SICI)1096-911X(199705)28:5<342::AID-MPO3>3.0.CO;2-H","article-title":"HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. 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