{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:41:43Z","timestamp":1783399303857,"version":"3.54.6"},"reference-count":153,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Reduced natural killer (NK) cell cytotoxicity is the most consistent immune finding in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS). Meta-analysis of the published literature determined the effect size of the decrement in ME\/CFS. Databases were screened for papers comparing NK cell cytotoxicity in ME\/CFS and healthy controls. A total of 28 papers and 55 effector:target cell ratio (E:T) data points were collected. Cytotoxicity in ME\/CFS was significantly reduced to about half of healthy control levels, with an overall Hedges\u2019 g of 0.96 (0.75\u20131.18). Heterogeneity was high but was explained by the range of E:T ratios, different methods, and potential outliers. The outcomes confirm reproducible NK cell dysfunction in ME\/CFS and will guide studies using the NK cell model system for pathomechanistic investigations.<\/jats:p><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:uri>, identifier CRD42024542140.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1440643","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T04:23:50Z","timestamp":1729139030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis\/chronic fatigue syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"James N.","family":"Baraniuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Eaton-Fitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Marshall-Gradisnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-108-3-387","article-title":"Chronic fatigue syndrome: a working case definition","volume":"108","author":"Holmes","year":"1988","journal-title":"Ann Intern Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-12-199412150-00009","article-title":"The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group","volume":"121","author":"Fukuda","year":"1994","journal-title":"Ann Intern Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2011.02428.x","article-title":"Myalgic encephalomyelitis: international consensus criteria","volume":"270","author":"Carruthers","year":"2011","journal-title":"J Intern Med"},{"key":"B4","volume-title":"Beyond Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Redefining an Illness","year":"2015"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2006.042754","article-title":"Definitions and aetiology of myalgic encephalomyelitis: how the Canadian consensus clinical definition of myalgic encephalomyelitis works","volume":"60","author":"Carruthers","year":"2007","journal-title":"J Clin Pathol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1001\/jama.2023.8823","article-title":"Development of a definition of postacute sequelae of SARS-coV-2 infection","volume":"329","author":"Thaweethai","year":"2023","journal-title":"JAMA"},{"key":"B7","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.molmed.2021.06.002","article-title":"Insights from myalgic encephalomyelitis\/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome","volume":"27","author":"Komaroff","year":"2021","journal-title":"Trends Mol Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1187163","article-title":"ME\/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature","volume":"10","author":"Komaroff","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.139.10.3306","article-title":"Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome","volume":"139","author":"Caligiuri","year":"1987","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s13643-019-1202-6","article-title":"A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"8","author":"Eaton-Fitch","year":"2019","journal-title":"Syst Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910180405","article-title":"Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia","volume":"18","author":"Klein","year":"1976","journal-title":"Int J Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.28.6.1403-1410.1990","article-title":"Immunologic abnormalities in chronic fatigue syndrome","volume":"28","author":"Klimas","year":"1990","journal-title":"J Clin Microbiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1529-1049(01)00047-2","article-title":"Natural killer cell function in chronic fatigue syndrome","volume":"2","author":"Fletcher","year":"2002","journal-title":"Clin Appl Immunol Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02935.x","article-title":"Chronic fatigue syndrome is associated with diminished intracellular perforin","volume":"142","author":"Maher","year":"2005","journal-title":"Clin Exp Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010817","article-title":"Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV\/CD26","volume":"5","author":"Fletcher","year":"2010","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/(ISSN)1097-0320","article-title":"Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity","volume":"37","author":"Aubry","year":"1999","journal-title":"Cytometry"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/1099800403257196","article-title":"Natural killer cell cytotoxicity: a methods analysis of 51chromium release versus flow cytometry","volume":"5","author":"Motzer","year":"2003","journal-title":"Biol Res Nurs"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.9.4.747-752.2002","article-title":"Evidence for the presence of immune dysfunction in chronic fatigue syndrome","volume":"9","author":"Natelson","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"348","DOI":"10.4172\/2155-9899.1000348","article-title":"Low NK cell activity in chronic fatigue syndrome (CFS) and relationship to symptom severity","volume":"6","author":"Strayer","year":"2015","journal-title":"J Clin Cell Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.3.3.260-264.1996","article-title":"Effects of anticoagulant, serum, and temperature on the natural killer activity of human peripheral blood mononuclear cells stored overnight","volume":"3","author":"Son","year":"1996","journal-title":"Clin Diagn Lab Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.11124\/JBISRIR-D-19-00099","article-title":"Methodological quality of case series studies: an introduction to the JBI critical appraisal tool","volume":"18","author":"Munn","year":"2020","journal-title":"JBI Evid Synth"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/jech.52.6.377","article-title":"The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions","volume":"52","author":"Downs","year":"1978","journal-title":"J Epidemiol Community Health"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3129\/i08-001","article-title":"Age-related macular degeneration and low-vision rehabilitation: a systematic review","volume":"43","author":"Hooper","year":"2008","journal-title":"Can J Ophthalmol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"B25","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2288-5-13","article-title":"Estimating the mean and variance from the median, range, and the size of a sample","volume":"5","author":"Hozo","year":"2005","journal-title":"BMC Med Res Methodol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1429","article-title":"Optimally estimating the sample standard deviation from the five-number summary","volume":"11","author":"Shi","year":"2020","journal-title":"Res Synth Methods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/09622802231172043","article-title":"Detecting the skewness of data from the five-number summary and its application in meta-analysis","volume":"32","author":"Shi","year":"2023","journal-title":"Stat Methods Med Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216669183","article-title":"Optimally estimating the sample mean from the sample size, median, mid-range, and\/or mid-quartile range","volume":"27","author":"Luo","year":"2018","journal-title":"Stat Methods Med Res"},{"key":"B29","unstructured":"Estimating the sample mean and standard deviation (SD) from the five-number summary and its application in meta-analysis2024"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2016.195","article-title":"An overview of meta-analysis for clinicians","volume":"33","author":"Lee","year":"2018","journal-title":"Korean J Intern Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/1471-2288-14-135","article-title":"Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range","volume":"14","author":"Wan","year":"2014","journal-title":"BMC Med Res Methodol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s12967-023-03958-2","article-title":"Natural killer cytotoxicity in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS): a multi-site clinical assessment of ME\/CFS (MCAM) sub-study","volume":"21","author":"Querec","year":"2023","journal-title":"J Transl Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.1860040207","article-title":"Natural killer cytotoxicity in the diagnosis of immune dysfunction: criteria for a reproducible assay","volume":"4","author":"Whiteside","year":"1990","journal-title":"J Clin Lab Anal"},{"key":"B34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/BF00915477","article-title":"Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity","volume":"1","author":"Pross","year":"1981","journal-title":"J Clin Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1260","article-title":"Introduction, comparison and validation of MetaEssentials: A free and simple tool for meta-analysis","volume":"8","author":"Suurmond","year":"2017","journal-title":"Res Synth Methods"},{"key":"B36","unstructured":"Meta-Essentials"},{"key":"B37","volume-title":"User manual for Meta-Essentials: Workbooks for meta-analysis (version 1.4)","author":"Van Rhee","year":"2015"},{"key":"B38","unstructured":"Chapter 10 Analysing Data and Undertaking meta-Analyses\n            DeeksJ\n            HigginsJ\n            AltmanD\n          Cochrane Handbook for Systematic Reviews of Interventions version 6.32022"},{"key":"B39","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2307\/3001666","article-title":"The combination of estimates from different experiments","volume":"10","author":"Cochran","year":"1954","journal-title":"Biometrics"},{"key":"B40","article-title":"Chronic fatigue syndrome\u2013a controlled cross sectional study","volume":"21","author":"Rasmussen","year":"1994","journal-title":"J Rheumatol"},{"key":"B41","article-title":"Chronic fatigue syndrome\u2013study of 51 cases treated at the Second Tokyo National Hospital","volume":"50","author":"Nishikai","year":"1992","journal-title":"Nihon Rinsho"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1998.00373.x","article-title":"Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome","volume":"28","author":"Ogawa","year":"1998","journal-title":"Eur J Clin Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2006.03.001","article-title":"Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup","volume":"60","author":"Siegel","year":"2006","journal-title":"J Psychosom Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1300\/J092v11n02_06","article-title":"Clinical improvement in chronic fatigue syndrome is associated with enhanced natural killer cell-mediated cytotoxicity: the results of a pilot study with isoprinosine\u00ae","volume":"11","author":"Diaz-Mitoma","year":"2003","journal-title":"J Chronic Fatigue Syndr"},{"key":"B45","doi-asserted-by":"publisher","first-page":"113049","DOI":"10.1016\/j.jim.2021.113049","article-title":"Evaluation of natural killer cell assay performance on shipped blood specimens","volume":"495","author":"Querec","year":"2021","journal-title":"J Immunol Methods"},{"key":"B46","doi-asserted-by":"crossref","DOI":"10.1159\/000416310","article-title":"Natural killer cell activity in the chronic fatigue\u2013immune dysfunction syndrome","author":"Eby","year":"1989"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/S0033-3182(91)72060-4","article-title":"The effects of a laboratory stressor on natural killer cell function in chronic fatigue syndrome patients","volume":"32","author":"Wemm","year":"1991","journal-title":"Psychosomatics"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1993.00410010136014","article-title":"Clinical and immunologic study of 205 patients with chronic fatigue syndrome: a case series from Italy","volume":"153","author":"Tirelli","year":"1993","journal-title":"Arch Intern Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00723","article-title":"Unperturbed cytotoxic lymphocyte phenotype and function in myalgic encephalomyelitis\/chronic fatigue syndrome patients","volume":"8","author":"Theorell","year":"2017","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1001\/jama.1990.03450010052029","article-title":"Chronic fatigue. A prospective clinical and virologic study","volume":"264","author":"Gold","year":"1990","journal-title":"JAMA"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1993.1178","article-title":"Low NK syndrome and its relationship to chronic fatigue syndrome","volume":"69","author":"Aoki","year":"1993","journal-title":"Clin Immunol Immunopathol"},{"key":"B52","article-title":"Low natural killer syndrome: clinical and immunologic features","volume":"6","author":"Aoki","year":"1987","journal-title":"Nat Immun Cell Growth Regul"},{"key":"B53","volume-title":"Stress, Coping, and Infectius Illness: Persistently Low Natural Killer Cell Activity as a Host Risk Factor. Annual Report","author":"Levy","year":"1988"},{"key":"B54","article-title":"Persistently low natural killer cell activity in normal adults: immunological, hormonal and mood correlates","volume":"8","author":"Levy","year":"1989","journal-title":"Nat Immun Cell Growth Regul"},{"key":"B55","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/1479-5876-11-68","article-title":"B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome","volume":"11","author":"Curriu","year":"2013","journal-title":"J Transl Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01028","article-title":"Association of T and NK cell phenotype with the diagnosis of myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS)","volume":"9","author":"Rivas","year":"2018","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s13317-013-0051-x","article-title":"Natural killer cells in patients with severe chronic fatigue syndrome","volume":"4","author":"Brenu","year":"2013","journal-title":"Auto Immun Highlights"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00796","article-title":"Cellular immune function in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS)","volume":"10","author":"Cliff","year":"2019","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s40659-016-0087-2","article-title":"Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome\/Myalgic encephalomyelitis patients","volume":"49","author":"Nguyen","year":"2016","journal-title":"Biol Res"},{"key":"B60","first-page":"516","article-title":"The effect of F3 on natural killer cell activity in the patients with chronic fatigue syndrome","volume":"35","author":"Chu","year":"1994","journal-title":"Proc Am Assoc Cancer Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-3083.1989.tb01183.x","article-title":"Naloxone-reversible monocyte dysfunction in patients with chronic fatigue syndrome","volume":"30","author":"Prieto","year":"1989","journal-title":"Scand J Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910380620","article-title":"Specific inhibition of human natural killer cell-mediated cytotoxicity by sialic acid and sialo-oligosaccharides","volume":"38","author":"Van Rinsum","year":"1986","journal-title":"Int J Cancer"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(03)00193-9","article-title":"Natural killer cell functions mediated by the neuropeptide substance P","volume":"116","author":"Feistritzer","year":"2003","journal-title":"Regul Pept"},{"key":"B64","doi-asserted-by":"publisher","first-page":"11937","DOI":"10.3390\/ijms241511937","article-title":"Surveying the metabolic and dysfunctional profiles of T cells and NK cells in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"24","author":"Maya","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B65","first-page":"1","article-title":"A comparison of immune functionality in viral versus non-viral CFS subtypes","volume":"8","author":"Porter","year":"2010","journal-title":"J Behav Neurosci Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1086\/339194","article-title":"Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome","volume":"185","author":"Sabath","year":"2002","journal-title":"J Infect Dis"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1080\/21641846.2021.1876613","article-title":"Antibody-dependent cell-mediated cytotoxicity (ADCC) in familial myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS)","volume":"8","author":"Sung","year":"2020","journal-title":"Fatigue"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcl063","article-title":"A placebo-controlled, double-blind, randomized controlled trial of a natural killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome","volume":"99","author":"McDermott","year":"2006","journal-title":"QJM"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-199411000-00006","article-title":"Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome","volume":"56","author":"Masuda","year":"1994","journal-title":"Psychosom Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020423124675","article-title":"Psychosocial characteristics and immunological functions in patients with postinfectious chronic fatigue syndrome and noninfectious chronic fatigue syndrome","volume":"25","author":"Masuda","year":"2002","journal-title":"J Behav Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/175.1.136","article-title":"Immune responses associated with chronic fatigue syndrome: a case-control study","volume":"175","author":"Mawle","year":"1997","journal-title":"J Infect Dis"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/18.Supplement_1.S136","article-title":"Immunologic abnormalities associated with chronic fatigue syndrome","author":"Barker","year":"1994","journal-title":"Clin Infect Dis"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/18.Supplement_1.S157","article-title":"Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome","author":"Ojo-Amaize","year":"1994","journal-title":"Clin Infect Dis"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3109\/08820139609059298","article-title":"alpha-Interferon treatment of patients with chronic fatigue syndrome","volume":"25","author":"See","year":"1996","journal-title":"Immunol Invest"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(96)00125-7","article-title":"In vitro effects of eChinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients","volume":"35","author":"See","year":"1997","journal-title":"Immunopharmacology"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/BF02688668","article-title":"The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome","volume":"33","author":"See","year":"1998","journal-title":"Integr Physiol Behav Sci"},{"key":"B77","article-title":"Immunomodulatory effects of a homeopathic agent","author":"See","year":"1998"},{"key":"B78","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1006\/clin.1998.4554","article-title":"Dysfunction of natural killer activity in a family with chronic fatigue syndrome","volume":"88","author":"Levine","year":"1998","journal-title":"Clin Immunol Immunopathol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt068","article-title":"Role of adaptive and innate immune cells in chronic fatigue syndrome\/myalgic encephalomyelitis","volume":"26","author":"Brenu","year":"2014","journal-title":"Int Immunol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12865-015-0101-4","article-title":"Characterisation of cell functions and receptors in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis (CFS\/ME)","volume":"16","author":"Hardcastle","year":"2015","journal-title":"BMC Immunol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/sji.12388","article-title":"Pilot study of natural killer cells in chronic fatigue syndrome\/myalgic encephalomyelitis and multiple sclerosis","volume":"83","author":"Huth","year":"2016","journal-title":"Scand J Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2012.03.037","article-title":"Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis","volume":"141","author":"Brenu","year":"2012","journal-title":"J Affect Disord"},{"key":"B83","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/1479-5876-9-81","article-title":"Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis","volume":"9","author":"Brenu","year":"2011","journal-title":"J Transl Med"},{"key":"B84","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/1479-5876-10-88","article-title":"Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome\/myalgic encephalomyelitis","volume":"10","author":"Brenu","year":"2012","journal-title":"J Transl Med"},{"key":"B85","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2147\/TACG","article-title":"Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"9","author":"Marshall-Gradisnik","year":"2016","journal-title":"Appl Clin Genet"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12882","article-title":"Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome\/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels","volume":"187","author":"Nguyen","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40360-018-0203-8","article-title":"Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis patients: A pilot in vitro investigation","volume":"19","author":"Eaton","year":"2018","journal-title":"BMC Pharmacol Toxicol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1186\/s12967-019-02155-4","article-title":"Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis\/chronic fatigue syndrome patients","volume":"17","author":"Balinas","year":"2019","journal-title":"J Transl Med"},{"key":"B89","doi-asserted-by":"publisher","first-page":"11879","DOI":"10.3390\/ijerph182211879","article-title":"Characterization of IL-2 stimulation and TRPM7 pharmacomodulation in NK cell cytotoxicity and channel co-localization with PIP2 in myalgic encephalomyelitis\/chronic fatigue syndrome patients","volume":"18","author":"Du Preez","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B90","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s12967-021-02974-4","article-title":"The effect of IL-2 stimulation and treatment of TRPM3 on channel co-localisation with PIP2 and NK cell function in myalgic encephalomyelitis\/chronic fatigue syndrome patients","volume":"19","author":"Eaton-Fitch","year":"2021","journal-title":"J Transl Med"},{"key":"B91","doi-asserted-by":"publisher","first-page":"27S","DOI":"10.1016\/S0002-9343(98)00155-7","article-title":"Natural killer cells and natural killer cell activity in chronic fatigue syndrome","volume":"105","author":"Whiteside","year":"1998","journal-title":"Am J Med"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.12399","article-title":"Serum immune proteins in moderate and severe chronic fatigue syndrome\/myalgic encephalomyelitis patients","volume":"12","author":"Hardcastle","year":"2015","journal-title":"Int J Med Sci"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1479-5876-8-1","article-title":"Immune and hemorheological changes in chronic fatigue syndrome","volume":"8","author":"Brenu","year":"2010","journal-title":"J Transl Med"},{"key":"B94","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12967-016-0859-z","article-title":"ERK1\/2, MEK1\/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim\/- natural killer cells in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis patients","volume":"14","author":"Huth","year":"2016","journal-title":"J Transl Med"},{"key":"B95","volume-title":"Exploratory Data Analysis","author":"Tukey","year":"1977"},{"key":"B96","volume-title":"Methods for Meta-analysis in Medical Research","author":"Sutton","year":"2000"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12817","article-title":"Quantifying publication bias in meta-analysis","volume":"74","author":"Lin","year":"2018","journal-title":"Biometrics"},{"key":"B98","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1037\/1082-989X.3.1.46","article-title":"Using the normal quantile plot to explore meta-analytic data sets","volume":"3","author":"Wang","year":"1998","journal-title":"Psychol Methods"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(01)00377-8","article-title":"Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis","volume":"54","author":"Sterne","year":"2001","journal-title":"J Clin Epidemiol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1097-0258","article-title":"Models for estimating the number of unpublished studies","volume":"15","author":"Gleser","year":"1996","journal-title":"Stat Med"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.86.3.638","article-title":"The file drawer problem and tolerance for null results","volume":"86","author":"Rosenthal","year":"1979","journal-title":"Psychol Bull"},{"key":"B102","volume-title":"Statistical Methods for Research Workers","author":"Fisher","year":"1925"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.01.012","article-title":"An impedance-based cytotoxicity assay for real-time and label-free assessment of T-cell-mediated killing of adherent cells","volume":"405","author":"Peper","year":"2014","journal-title":"J Immunol Methods"},{"key":"B104","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/cyto.a.10081","article-title":"Cell-mediated cytotoxicity evaluation using monoclonal antibody staining for target or effector cells with annexinV\/propidium iodide colabeling by fluorosphere-adjusted counts on three-color flow cytometry","volume":"56","author":"Ozdemir","year":"2003","journal-title":"Cytom A"},{"key":"B105","first-page":"13","article-title":"Flow cytometric non-radioactive method for the determination of the cytotoxic activity of natural killer cells: Comparison with the classical 51Cr-release assay","volume":"21","author":"Lotzerich","year":"1997","journal-title":"Laboratoriums Medizin"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jim.2014.01.017","article-title":"Effects of cryopreservation on effector cells for antibody dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell activity in (51)Cr-release and CD107a assays","volume":"406","author":"Mata","year":"2014","journal-title":"J Immunol Methods"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90104-X","article-title":"Standardization of a micro-cytotoxicity assay for human natural killer cell lytic activity","volume":"172","author":"Mariani","year":"1994","journal-title":"J Immunol Methods"},{"key":"B108","article-title":"An improved flow cytometry-based natural killer cytotoxicity assay involving calcein AM staining of effector cells","volume":"42","author":"Jang","year":"2012","journal-title":"Ann Clin Lab Sci"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.4.2.202-207.1997","article-title":"Comparison of europium and chromium release assays: cytotoxicity in healthy individuals and patients with cervical carcinoma","volume":"4","author":"von Zons","year":"1997","journal-title":"Clin Diagn Lab Immunol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2160-8_16","article-title":"NK cell isolation and cytotoxicity by radioactive chromium release assay and DELFIA-euTDA cytotoxicity assay","volume":"2463","author":"Buller","year":"2022","journal-title":"Methods Mol Biol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"e23519","DOI":"10.1002\/jcla.23519","article-title":"A novel CD2 staining-based flow cytometric assay for assessment of natural killer cell cytotoxicity","volume":"34","author":"Zhang","year":"2020","journal-title":"J Clin Lab Anal"},{"key":"B112","doi-asserted-by":"publisher","first-page":"112992","DOI":"10.1016\/j.jim.2021.112992","article-title":"Non-invasive image-based cytometry for high throughput NK cell cytolysis analysis","volume":"491","author":"Patel","year":"2021","journal-title":"J Immunol Methods"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141074","article-title":"A novel method for assessment of natural killer cell cytotoxicity using image cytometry","volume":"10","author":"Somanchi","year":"2015","journal-title":"PloS One"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-439851","article-title":"Classification of human natural killer cells based on migration behavior and cytotoxic response","volume":"121","author":"Vanherberghen","year":"2013","journal-title":"Blood"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00119","article-title":"Microchip screening platform for single cell assessment of NK cell cytotoxicity","volume":"7","author":"Guldevall","year":"2016","journal-title":"Front Immunol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"17084","DOI":"10.1038\/s41598-021-96609-9","article-title":"An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip","volume":"11","author":"Subedi","year":"2021","journal-title":"Sci Rep"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13091","article-title":"Intermittent and graded exercise effects on NK cell degranulation markers LAMP-1\/LAMP-2 and CD8+CD38+ in chronic fatigue syndrome\/myalgic encephalomyelitis","volume":"5","author":"Broadbent","year":"2017","journal-title":"Physiol Rep"},{"key":"B118","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jim.2005.09.005","article-title":"A differential assay of NK-cell-mediated cytotoxicity in K562 cells revealing three sequential membrane impairment steps using three-color flow-cytometry","volume":"307","author":"Kasatori","year":"2005","journal-title":"J Immunol Methods"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.582330","article-title":"Impact of long-term cryopreservation on blood immune cell markers in myalgic encephalomyelitis\/chronic fatigue syndrome: implications for biomarker discovery","volume":"11","author":"G\u00f3mez-Mora","year":"2020","journal-title":"Front Immunol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1993.33893342746.x","article-title":"Differential effect of cryopreservation on natural killer cell and lymphokine-activated killer cell activities","volume":"33","author":"Mart\u00ed","year":"1993","journal-title":"Transfusion (Paris)"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-021-00494-7","article-title":"Cryopreservation of NK and T cells without DMSO for adoptive cell-based immunotherapy","volume":"35","author":"Yao","year":"2021","journal-title":"BioDrugs"},{"key":"B122","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1128\/CDLI.6.1.6-13.1999","article-title":"Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome","volume":"6","author":"Zhang","year":"1999","journal-title":"Clin Diagn Lab Immunol"},{"key":"B123","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/cyto.b.10034","article-title":"Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome","volume":"53","author":"Stewart","year":"2003","journal-title":"Cytom B Clin Cytom"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02833.x","article-title":"Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression","volume":"141","author":"Robertson","year":"2005","journal-title":"Clin Exp Immunol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000699","article-title":"Diversity of peripheral blood human NK cells identified by single-cell RNA sequencing","volume":"4","author":"Smith","year":"2020","journal-title":"Blood Adv"},{"key":"B126","doi-asserted-by":"publisher","first-page":"3931","DOI":"10.1038\/s41467-019-11947-7","article-title":"Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome","volume":"10","author":"Yang","year":"2019","journal-title":"Nat Commun"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23772","article-title":"Glucagon-like peptide-1 therapy in people with obesity restores natural killer cell metabolism and effector function","volume":"31","author":"De Barra","year":"2023","journal-title":"Obes (Silver Spring)"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.687806","article-title":"Potential therapeutic benefit of low dose naltrexone in myalgic encephalomyelitis\/chronic fatigue syndrome: role of transient receptor potential melastatin 3 ion channels in pathophysiology and treatment","volume":"12","author":"Cabanas","year":"2021","journal-title":"Front Immunol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02545","article-title":"Naltrexone restores impaired transient receptor potential melastatin 3 ion channel function in natural killer cells from myalgic encephalomyelitis\/chronic fatigue syndrome patients","volume":"10","author":"Cabanas","year":"2019","journal-title":"Front Immunol"},{"key":"B130","first-page":"289","article-title":"Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity","volume":"10","author":"Levy","year":"1991","journal-title":"Nat Immun Cell Growth Regul"},{"key":"B131","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1006\/cimm.1994.1112","article-title":"Effects of aging on natural killer cell activity and activation by interleukin-2 and IFN-alpha","volume":"155","author":"Kutza","year":"1994","journal-title":"Cell Immunol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.07.020","article-title":"Natural killer cell deficiency","volume":"132","author":"Orange","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700038617","article-title":"Depression and reduced natural killer cytotoxicity: a longitudinal study of depressed patients and control subjects","volume":"22","author":"Irwin","year":"1992","journal-title":"Psychol Med"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820050052009","article-title":"Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression","volume":"49","author":"Evans","year":"1992","journal-title":"Arch Gen Psychiatry"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(91)90183-M","article-title":"Reduced natural killer cell cytotoxicity in depression but not in schizophrenia","volume":"30","author":"Caldwell","year":"1991","journal-title":"Biol Psychiatry"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1990.01810200021003","article-title":"Major depressive disorder, alcoholism, and reduced natural killer cell cytotoxicity. Role of severity of depressive symptoms and alcohol consumption","volume":"47","author":"Irwin","year":"1990","journal-title":"Arch Gen Psychiatry"},{"key":"B137","article-title":"Contrasting Case Definitions: The ME International Consensus Criteria vs. the Fukuda et\u00a0al. CFS Criteria","volume":"15","author":"Brown","year":"2013","journal-title":"N Am J Psychol"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2022.2043462","article-title":"Evaluating case diagnostic criteria for myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS): toward an empirical case definition","volume":"45","author":"Conroy","year":"2023","journal-title":"Disabil Rehabil"},{"key":"B139","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1472-6963-3-25","article-title":"Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution","volume":"3","author":"Reeves","year":"2003","journal-title":"BMC Health Serv Res"},{"key":"B140","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/1741-7015-7-57","article-title":"An evaluation of exclusionary medical\/psychiatric conditions in the definition of chronic fatigue syndrome","volume":"7","author":"Jones","year":"2009","journal-title":"BMC Med"},{"key":"B141","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1086\/313908","article-title":"Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study","volume":"31","author":"Reeves","year":"2000","journal-title":"Clin Infect Dis"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-2-103","article-title":"A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection","volume":"116","author":"Buchwald","year":"1992","journal-title":"Ann Intern Med"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(99)00079-7","article-title":"Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients","volume":"16","author":"Ablashi","year":"2000","journal-title":"J Clin Virol"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(06)70011-7","article-title":"Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome","author":"Chapenko","year":"2006","journal-title":"J Clin Virol"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.565","article-title":"Are natural killer cells protecting the metabolically healthy obese patient","volume":"17","author":"Lynch","year":"2009","journal-title":"Obes (Silver Spring)"},{"key":"B146","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/cancers11040573","article-title":"Dysregulation of natural killer cells in obesity","volume":"11","author":"O\u2019Shea","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.01.007","article-title":"Alteration of Natural Killer cell phenotype and function in obese individuals","volume":"177","author":"Viel","year":"2017","journal-title":"Clin Immunol"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.573200","article-title":"Characterization of surface receptor expression and cytotoxicity of human NK cells and NK cell subsets in overweight and obese humans","volume":"11","author":"Naujoks","year":"2020","journal-title":"Front Immunol"},{"key":"B149","doi-asserted-by":"publisher","first-page":"2715","DOI":"10.1038\/s41598-023-29731-5","article-title":"Butyrate limits human natural killer cell effector function","volume":"13","author":"Zaiatz-Bittencourt","year":"2023","journal-title":"Sci Rep"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0251-7","article-title":"Metabolic reprogramming of natural killer cells in obesity limits antitumor responses","volume":"19","author":"Michelet","year":"2018","journal-title":"Nat Immunol"},{"key":"B151","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s10020-022-00528-y","article-title":"Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis\/chronic fatigue syndrome patients","volume":"28","author":"Sasso","year":"2022","journal-title":"Mol Med"},{"key":"B152","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1755-8794-2-12","article-title":"Impaired immune function in Gulf War Illness","volume":"2","author":"Whistler","year":"2009","journal-title":"BMC Med Genomics"},{"key":"B153","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0232475","article-title":"A systematic review of neurological impairments in myalgic encephalomyelitis\/chronic fatigue syndrome using neuroimaging techniques","volume":"15","author":"Maksoud","year":"2020","journal-title":"PloS One"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1440643\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T04:24:01Z","timestamp":1729139041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1440643\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,17]]},"references-count":153,"alternative-id":["10.3389\/fimmu.2024.1440643"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1440643","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,17]]},"article-number":"1440643"}}