A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome

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.

Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched

“…Our scoping review included 1161 studies, and although our scope was larger than the 2008 review, there is a clear increase in research in the field. However, our findings echo the conclusions of numerous recent reviews [ 3 , 12 , 15 , 16 , 23 , 27 , 29 ], namely, that our confidence in the evidence is too low to draw conclusions about causal factors. This is due to the preponderance of relatively weak study designs.…”

“…The vastness of the research field on etiological factors reflects the variety of causal hypotheses [ 19 ], and in the past two years alone, numerous systematic reviews have been published examining distinct causal factors such as immunological [ 12 , 16 , 29 ], metabolic [ 15 , 23 ], circulatory [ 27 ], and epigenetic factors [ 3 ]. In 2016, the Research Council of Norway selected the CFS/ME field as the pilot field for a research priority setting partnership strategy, in which patients, next of kin, and related organizations prioritized research questions for commissioned research [ 14 ].…”

A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease

“…This impairment may aggravate the production of reactive oxygen species and contribute to the decline of mitochondrial processes, both observed in other studies [41]. Impaired NK cell cytotoxicity is the most consistently described feature in ME/CFS/SEID [42]. Mitochondrial dysfunction may therefore be a consequence, rather than a primary causative factor, in ME/CFS/SEID [44].…”

Systematic Review of Sleep Characteristics in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Melatonin levels influence multiple physiological processes including immune cell pathways [ 48 ]. As the most consistent immunological feature of ME/CFS is reduced natural killer (NK) cell cytotoxicity, this area will benefit from additional research [ 49 ]. Dysregulation of 2-5A synthetase/RNase L antiviral pathway has been previously linked with sleep disruption in particular changes to alpha delta sleep, however, investigations by Van Hoof et al did not support associations [ 50 ].…”