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Article

Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis

1
Department of Laboratory Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon 22711, Korea
2
Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
3
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591, Korea
4
Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary′s Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
5
Samkwang Medical Laboratories, Seoul 06742, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5413; https://doi.org/10.3390/ijms20215413
Received: 20 September 2019 / Revised: 28 October 2019 / Accepted: 28 October 2019 / Published: 30 October 2019
(This article belongs to the Special Issue Natural Killer and NKT Cells)
Although natural killer (NK) cell function is a hallmark of hemophagocytic lymphohistiocytosis (HLH), there is no standard method or data on its diagnostic value in adults. Thus, we performed a single-center retrospective study of 119 adult patients with suspected HLH. NK cell function was determined using both flowcytometry-based NK-cytotoxicity test (NK-cytotoxicity) and NK cell activity test for interferon-gamma (NKA-IFNγ). NK cell phenotype and serum cytokine levels were also tested. Fifty (42.0%) HLH patients showed significantly reduced NK cell function compared to 69 non-HLH patients by both NK-cytotoxicity and NKA-IFNγ (p < 0.001 and p = 0.020, respectively). Agreement between NK-cytotoxicity and NKA-IFNγ was 88.0% in HLH patients and 58.0% in non-HLH patients. NK-cytotoxicity and NKA-IFNγ assays predicted HLH with sensitivities of 96.0% and 92.0%, respectively. The combination of NKA-IFNγ and ferritin (>10,000 µg/L) was helpful for ruling out HLH, with a specificity of 94.2%. Decreased NK-cytotoxicity was associated with increased soluble IL-2 receptor levels and decreased CD56dim NK cells. Decreased NKA-IFNγ was associated with decreased serum cytokine levels. We suggest that both NK-cytotoxicity and NKA-IFNγ could be used for diagnosis of HLH. Further studies are needed to validate the diagnostic and prognostic value of NK cell function tests. View Full-Text
Keywords: hemophagocytic lymphohistiocytosis; natural killer cell activity; interferon-gamma; cytotoxicity; cytokine; NK cell subset hemophagocytic lymphohistiocytosis; natural killer cell activity; interferon-gamma; cytotoxicity; cytokine; NK cell subset
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MDPI and ACS Style

Lee, H.; Kim, H.S.; Lee, J.-M.; Park, K.H.; Choi, A.-R.; Yoon, J.-H.; Ryu, H.; Oh, E.-J. Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis. Int. J. Mol. Sci. 2019, 20, 5413. https://doi.org/10.3390/ijms20215413

AMA Style

Lee H, Kim HS, Lee J-M, Park KH, Choi A-R, Yoon J-H, Ryu H, Oh E-J. Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis. International Journal of Molecular Sciences. 2019; 20(21):5413. https://doi.org/10.3390/ijms20215413

Chicago/Turabian Style

Lee, Hyeyoung, Hoon S. Kim, Jong-Mi Lee, Ki H. Park, Ae-Ran Choi, Jae-Ho Yoon, Hyejin Ryu, and Eun-Jee Oh. 2019. "Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis" International Journal of Molecular Sciences 20, no. 21: 5413. https://doi.org/10.3390/ijms20215413

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