Abstract
BackgroundCompromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other outcomes evaluated in NK cells of ME/CFS patients, however, remain equivocal. The aim of this study was to conduct a systematic review of the literature regarding NK cell phenotype, receptor expression, cytokine production and cytotoxicity in ME/CFS patients and determine the appropriateness as a model for ME/CFS.MethodsMedline (EBSCOHost), Scopus, EMBASE and PubMed databases were systematically searched to source relevant papers published between 1994 and March 2018. This review included studies examining NK cells’ features in ME/CFS patients compared with HC following administration of specific inclusion and exclusion criteria. Secondary outcomes included genetic analysis in isolated NK cells or quality of life assessment. Quality assessment was completed using the Downs and Black checklist in addition to The Joanna Briggs Institute checklist.ResultsSeventeen eligible publications were included in this review. All studies were observational case control studies. Of these, 11 investigated NK cell cytotoxicity, 14 investigated NK cell phenotype and receptor profiles, three examined NK cell cytokine production, six investigated NK cell lytic protein levels and four investigated NK cell degranulation. Impaired NK cell cytotoxicity remained the most consistent immunological report across all publications. Other outcomes investigated differed between studies.ConclusionA consistent finding among all papers included in this review was impaired NK cell cytotoxicity, suggesting that it is a reliable and appropriate cellular model for continued research in ME/CFS patients. Aberrations in NK cell lytic protein levels were also reported. Although additional research is recommended, current research provides a foundation for subsequent investigations. It is possible that NK cell abnormalities can be used to characterise a subset of ME/CFS due to the heterogeneity of both the illness itself and findings between studies investigating specific features of NK function.
Highlights
Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Titles and abstracts were screened according to the following criteria by two authors (NEF and healthy controls (HC)): (i) all studies reported on NK cell cytotoxicity, NK cell phenotype or receptor profiles, mitogen-activated protein kinases (MAPK) phosphorylation, degranulation or lytic proteins in Myalgic encephalomyelitis (ME)/CFS patients compared with HC as their primary outcome; (ii) studies were published between 1994 and 2018 to exclude non-Fukuda-based case definitions; (iii) ME/CFS diagnosis fulfilled either Fukuda, Canadian Consensus Criteria (CCC) or International Consensus Criteria (ICC); (iv) human studies in adults age 18 years and above; (v) free full text publications available through institutional access; and (vi) based upon original research
This paper reported significant reductions in NK cell cytotoxicity in ME/CFS patients compared with HC at 0 month, 6 months and 12 months (p < 0.05)
Summary
Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Myalgic encephalomyelitis (ME), referred to as chronic fatigue syndrome (CFS), is a clinically defined condition characterised by profound dysregulation of the central nervous system and immune system [1, 2], endocrine dysfunction [3], and impaired cellular energy metabolism and ion transport [4, 5]. Diagnosis currently relies on the exclusion of all other possible fatigue-related illnesses and identification of ME/CFS cases using various symptom-based criteria [7,8,9]. A case of ME/CFS is defined under these criteria by the presence of unexplainable chronic fatigue that is not alleviated by rest. Post-exertional neuroimmune exhaustion accompanied by numerous neurological, autonomic and neuroendocrine manifestations are notable elements of these revised definitions necessary to formally diagnose a case of ME/CFS
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