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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

Author

Year

Assessed

Method

Increased in ME/CFS vs. HC (p value)

Decreased in ME/CFS vs. HC (p value)

No significance

Brenu et al. [42]

2010

NK cell phenotypes

Flow cytometry

 

CD56Bright (p < 0.05)

CD56Dim

NK cell cytotoxicity

 

K562% lysis (p < 0.05)

 

Brenu et al. [2]

2011

NK cell phenotypes

Flow cytometry

 

CD56Bright (p < 0.001)

CD56Dim

NK cell cytotoxicity

 

K562% lysis (p < 0.05)

 

Brenu et al. [43]

2012

NK cell phenotypes

Flow cytometry

 

CD56Bright (p = 0.02)a

CD56Dim

NK cell cytotoxicity

 

K562% lysis (p < 0.05)a

 

Brenu et al. [14]

2013

NK cell phenotypes

Flow cytometry

  

CD56Bright, CD56Dim

KIR, NKG2D

NK cell cytotoxicity

 

K562% (p < 0.05)

 

NK cell degranulation

CD107a (p < 0.05)

  

NK cell lytic proteins

 

Granzyme B (p < 0.05)

Perforin, Granzyme A

NK cell cytokine production

IFN-y (p < 0.05)

  

Curriu et al. [48]

2013

NK cell phenotypes

Flow cytometry

CD69 (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]

2010

NK cell cytotoxicity

51Cr release

 

51Cr (p < 0.000)

 

Hardcastle et al. [46]

2015

NK cell phenotype

Flow cytometry

KIR3DL1/DL2 (p < 0.004)a

KIR2DL1 (p = 0.011)a

KIR2DL2/DL3 (0.049)a

KIR2DS4 (0.023)a

CD18+CD11c

(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]

2014

NK cell phenotype

Flow cytometry

 

CD56BrightCD2+CD18+ (p < 0.01)

CD56DimCD18+CD11a+CD11c+ (p < 0.05)

CD56DimCD2+CD18+

CD18+CD11a+CD11b+CD11c+

NK cell degranulation

  

CD107a/b

NK cell lytic proteins

 

CD56Dim Granzyme B (p < 0.05)

Granzyme A, Perforin

Huth et al. [16]

2016

NK cell MAPK phosphorylation

Flow cytometry

MEK1/2 (p < 0.05)

P38 (p < 0.05)

ERK1/2 (p < 0.05)

MEK1/2

P38

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

TNF-α

GM-CSF

Maher et al. [20]

2005

NK cell phenotype

Flow cytometry

 

CD56+CD3 (p = 0.04)

 

NK cell cytotoxicity

51Cr release

 

51Cr (p = 0.001)

 

NK cell lytic proteins

Flow cytometry

 

Perforin (p = 0.01)

 

Marshall-Gradisnik et al. [44]

2016

NK cell cytotoxicity

Flow cytometry

 

K562% lysis (p < 0.05).

 

Nguyen et al. [49]

2016

NK cell phenotype

Flow 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]

2017

NK cell phenotype

Flow cytometry

CD56DimTRPM3+ (p < 0.01)c

TRPM3+ expression in CD56Bright (p < 0.05)

CD69 (p < 0.05)c

CD69

NK cell degranulation

  

CD107a

NK cell Ca2+ influx

CD56Bright (p < 0.05)c

 

CD56Dim

NK cell cytotoxicity

K562% lysis (p < 0.05)c

  

Rivas et al. [51]

2018

NK cell phenotype

Flow cytometry

CD69 (p = 0.0011)

CD56Bright (p = 0.0075)

NKG2C (p < 0.0001)

 

Stewart et al. [50]

2003

NK cell phenotype

Flow cytometry

 

CD56BrightCD8+ (p = 0.04)

CD56BrightCD8 (p = 0.05)d

 

Theorell et al. [47]

2017

NK cell phenotype

Flow cytometry

CD56Dim HLA-DR (p = 0.002)d

  

NK cell cytotoxicity

51Cr release

  

K562% lysis

IFN-γ inhibition (p = 0.004, 0.009)c

NK cell lytic proteins

Flow cytometry

  

Perforin, Granzyme A/B

NK cell cytokines

CD56Dim 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