. 2019 Nov 14;8:279. doi: 10.1186/s13643-019-1202-6

Table 2.

Summary of primary outcome results

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		CD56^Bright (p < 0.05)	CD56^Dim
Brenu et al. [42]	2010	NK cell cytotoxicity	Flow cytometry		K562% lysis (p < 0.05)
Brenu et al. [2]	2011	NK cell phenotypes	Flow cytometry		CD56^Bright (p < 0.001)	CD56^Dim
Brenu et al. [2]	2011	NK cell cytotoxicity	Flow cytometry		K562% lysis (p < 0.05)
Brenu et al. [43]	2012	NK cell phenotypes	Flow cytometry		CD56^Bright (p = 0.02)^a	CD56^Dim
Brenu et al. [43]	2012	NK cell cytotoxicity	Flow cytometry		K562% lysis (p < 0.05)^a
Brenu et al. [14]	2013	NK cell phenotypes	Flow cytometry			CD56^Bright, CD56^Dim 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) CD25CD56^Bright (p = 0.0012) CD25CD56^Dim (p = 0.0494)	CD56^Bright, CD56^Dim CD57 (p = 0.1942)
Curriu et al. [48]	2013	NK cell cytotoxicity	Flow cytometry			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)	CD56^BrightNKG2D (p = 0.014) KIR2DL2/DL3 (p = 0.045)^a NKp46 (p = 0.021)
Hardcastle et al. [46]	2015	NK cell lytic proteins	Flow cytometry			Perforin, granzyme A, granzyme B
Huth et al. [21]	2014	NK cell phenotype	Flow cytometry		CD56^BrightCD2⁺CD18⁺ (p < 0.01) CD56^DimCD18⁺CD11a⁺CD11c⁺ (p < 0.05)	CD56^DimCD2⁺CD18⁺ CD18⁺CD11a⁺CD11b⁺CD11c⁺
		NK cell degranulation				CD107a/b
		NK cell lytic proteins			CD56^Dim 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				CD56^Bright, CD56^Dim
		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 CD56^Bright (p < 0.05)	TRPM3⁺ expression in CD56^Dim
Nguyen et al. [49]	2016	NK cell Ca²⁺ influx	Flow cytometry		CD56^Bright (p < 0.05)^c
Nguyen et al. [5]	2017	NK cell phenotype	Flow cytometry	CD56^DimTRPM3⁺ (p < 0.01)^c	TRPM3⁺ expression in CD56^Bright (p < 0.05) CD69 (p < 0.05)^c	CD69
		NK cell degranulation				CD107a
		NK cell Ca²⁺ influx		CD56^Bright (p < 0.05)^c		CD56^Dim
		NK cell cytotoxicity		K562% lysis (p < 0.05)^c
Rivas et al. [51]	2018	NK cell phenotype	Flow cytometry	CD69 (p = 0.0011) CD56^Bright (p = 0.0075)	NKG2C (p < 0.0001)
Stewart et al. [50]	2003	NK cell phenotype	Flow cytometry		CD56^BrightCD8⁺ (p = 0.04) CD56^BrightCD8⁻ (p = 0.05)^d
Theorell et al. [47]	2017	NK cell phenotype	Flow cytometry	CD56^Dim 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		CD56^Dim IFNγ (p = 0.009)^c
		NK cell degranulation				CD107a

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

^aSignificance dependent on longitudinal data

^bSignificance is NK cell phenotype dependent

^cSignificance reported post pharmacological stimulation

^dSignificance dependent on geographical location