Cargando…

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

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 determine...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Hyeyoung, Kim, Hoon Seok, Lee, Jong-Mi, Park, Ki Hyun, Choi, Ae-Ran, Yoon, Jae-Ho, Ryu, Hyejin, Oh, Eun-Jee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862274/
https://www.ncbi.nlm.nih.gov/pubmed/31671661
http://dx.doi.org/10.3390/ijms20215413
_version_ 1783471516506128384
author Lee, Hyeyoung
Kim, Hoon Seok
Lee, Jong-Mi
Park, Ki Hyun
Choi, Ae-Ran
Yoon, Jae-Ho
Ryu, Hyejin
Oh, Eun-Jee
author_facet Lee, Hyeyoung
Kim, Hoon Seok
Lee, Jong-Mi
Park, Ki Hyun
Choi, Ae-Ran
Yoon, Jae-Ho
Ryu, Hyejin
Oh, Eun-Jee
author_sort Lee, Hyeyoung
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6862274
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68622742019-12-05 Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis Lee, Hyeyoung Kim, Hoon Seok Lee, Jong-Mi Park, Ki Hyun Choi, Ae-Ran Yoon, Jae-Ho Ryu, Hyejin Oh, Eun-Jee Int J Mol Sci Article 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. MDPI 2019-10-30 /pmc/articles/PMC6862274/ /pubmed/31671661 http://dx.doi.org/10.3390/ijms20215413 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Hyeyoung
Kim, Hoon Seok
Lee, Jong-Mi
Park, Ki Hyun
Choi, Ae-Ran
Yoon, Jae-Ho
Ryu, Hyejin
Oh, Eun-Jee
Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis
title Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis
title_full Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis
title_fullStr Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis
title_full_unstemmed Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis
title_short Natural Killer Cell Function Tests by Flowcytometry-Based Cytotoxicity and IFN-γ Production for the Diagnosis of Adult Hemophagocytic Lymphohistiocytosis
title_sort natural killer cell function tests by flowcytometry-based cytotoxicity and ifn-γ production for the diagnosis of adult hemophagocytic lymphohistiocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862274/
https://www.ncbi.nlm.nih.gov/pubmed/31671661
http://dx.doi.org/10.3390/ijms20215413
work_keys_str_mv AT leehyeyoung naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT kimhoonseok naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT leejongmi naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT parkkihyun naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT choiaeran naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT yoonjaeho naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT ryuhyejin naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis
AT oheunjee naturalkillercellfunctiontestsbyflowcytometrybasedcytotoxicityandifngproductionforthediagnosisofadulthemophagocyticlymphohistiocytosis