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Table 2 Summary of primary outcome results

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

AuthorYearAssessedMethodIncreased in ME/CFS vs. HC (p value)Decreased in ME/CFS vs. HC (p value)No significance
Brenu et al. [42]2010NK cell phenotypesFlow cytometry CD56Bright (p < 0.05)CD56Dim
NK cell cytotoxicity K562% lysis (p < 0.05) 
Brenu et al. [2]2011NK cell phenotypesFlow cytometry CD56Bright (p < 0.001)CD56Dim
NK cell cytotoxicity K562% lysis (p < 0.05) 
Brenu et al. [43]2012NK cell phenotypesFlow cytometry CD56Bright (p = 0.02)aCD56Dim
NK cell cytotoxicity K562% lysis (p < 0.05)a 
Brenu et al. [14]2013NK cell phenotypesFlow cytometry  CD56Bright, CD56Dim
NK cell cytotoxicity K562% (p < 0.05) 
NK cell degranulationCD107a (p < 0.05)  
NK cell lytic proteins Granzyme B (p < 0.05)Perforin, Granzyme A
NK cell cytokine productionIFN-y (p < 0.05)  
Curriu et al. [48]2013NK cell phenotypesFlow cytometryCD69 (p = 0.0004, p < 0.01)b
NKp46 (p < 0.001), (p = 0.0023)b
CD57 (p = 0.052) (MFI)
CD25CD56Bright (p = 0.0012)
CD25CD56Dim (p = 0.0494)
CD56Bright, CD56Dim
CD57 (p = 0.1942)
NK cell cytotoxicity  K562% lysis
Fletcher et al. [45]2010NK cell cytotoxicity51Cr release 51Cr (p < 0.000) 
Hardcastle et al. [46]2015NK cell phenotypeFlow cytometryKIR3DL1/DL2 (p < 0.004)a
KIR2DL1 (p = 0.011)a
KIR2DL2/DL3 (0.049)a
KIR2DS4 (0.023)a
(p = 0.036)
CD18+CD2 (p = 0.009)
SLAM (p = 0.046)
CD56BrightNKG2D (p = 0.014)
KIR2DL2/DL3 (p = 0.045)a
NKp46 (p = 0.021)
NK cell lytic proteins  Perforin, granzyme A, granzyme B
Huth et al. [21]2014NK cell phenotypeFlow cytometry CD56BrightCD2+CD18+ (p < 0.01)
CD56DimCD18+CD11a+CD11c+ (p < 0.05)
NK cell degranulation  CD107a/b
NK cell lytic proteins CD56Dim Granzyme B (p < 0.05)Granzyme A, Perforin
Huth et al. [16]2016NK cell MAPK phosphorylationFlow cytometryMEK1/2 (p < 0.05)
P38 (p < 0.05)
ERK1/2 (p < 0.05)MEK1/2
NK cell cytotoxicity K562% lysis 
NK cell degranulation  CD107a/b
NK cell lytic proteins  Perforin, Granzyme A, granzyme B
NK cell phenotype  CD56Bright, CD56Dim
NK cell cytokines  IFN-γ
Maher et al. [20]2005NK cell phenotypeFlow cytometry CD56+CD3 (p = 0.04) 
NK cell cytotoxicity51Cr release 51Cr (p = 0.001) 
NK cell lytic proteinsFlow cytometry Perforin (p = 0.01) 
Marshall-Gradisnik et al. [44]2016NK cell cytotoxicityFlow cytometry K562% lysis (p < 0.05). 
Nguyen et al. [49]2016NK cell phenotypeFlow cytometry TRPM3+ expression in CD56Bright (p < 0.05)TRPM3+ expression in CD56Dim
NK cell Ca2+ influx CD56Bright (p < 0.05)c 
Nguyen et al. [5]2017NK cell phenotypeFlow cytometryCD56DimTRPM3+ (p < 0.01)cTRPM3+ expression in CD56Bright (p < 0.05)
CD69 (p < 0.05)c
NK cell degranulation  CD107a
NK cell Ca2+ influxCD56Bright (p < 0.05)c CD56Dim
NK cell cytotoxicityK562% lysis (p < 0.05)c  
Rivas et al. [51]2018NK cell phenotypeFlow cytometryCD69 (p = 0.0011)
CD56Bright (p = 0.0075)
NKG2C (p < 0.0001) 
Stewart et al. [50]2003NK cell phenotypeFlow cytometry CD56BrightCD8+ (p = 0.04)
CD56BrightCD8 (p = 0.05)d
Theorell et al. [47]2017NK cell phenotypeFlow cytometryCD56Dim HLA-DR (p = 0.002)d  
NK cell cytotoxicity51Cr release  K562% lysis
IFN-γ inhibition (p = 0.004, 0.009)c
NK cell lytic proteinsFlow cytometry  Perforin, Granzyme A/B
NK cell cytokinesCD56Dim IFNγ (p = 0.009)c  
NK cell degranulation  CD107a
  1. ME myalgic encephalomyelitis, CFS chronic fatigue syndrome, HC healthy control, NK natural killer, Ca2+ calcium, NS no significance, TNF tumour necrosis factor, IFN interferon, MFI mean fluorescence intensity
  2. aSignificance dependent on longitudinal data
  3. bSignificance is NK cell phenotype dependent
  4. cSignificance reported post pharmacological stimulation
  5. dSignificance dependent on geographical location