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. 2022 Mar 9;28(4):548–582. doi: 10.1093/humupd/dmac006

Table III.

Uterine NK cell activity, by NK cell regulation and receptors.

Author/Year Study design Study groups and sample number Tissue analysed Method of analysis Outcome measure, e.g. receptor expression Direction of effect in RM/RIF patients
Kwak et al. (1999) Prospective case control

  • 71 uRM (n = 71)

  • vs

  • patients and STOP for healthy controls (n = 20)

 Decidual samples at ERPC (uRM patients) and STOP for healthy controls (all <12/40) IHC/histology

  • 30% of women with RM demonstrated increased NK cell infiltrates in maternal decidua at the implantation site.

  • No correlation between increased NK cell infiltrates at the implantation site with

  • (i) inadequate depth of invasion or

  • (ii) inadequate number of intermediate trophoblast

 Qualitative analysis
Emmer et al. (2002) Prospective Case Control RM (n = 9); 2 controls (n = 11) Decidual tissue at time of ERPC or TOP; 2 hysterectomy specimens IHC Expression of
• CD56 ↑
• CD16 ↑
Yan et al. (2007) Prospective case control

  • RM (n = 10)

  • vs

  • controls (n = 23)

 FC; semi-quantitative RT-PCR uNK expression of
• KIR2DL4 ↓
Qu et al. (2008) Prospective case control

  • RM (n = 22)

  • vs

  • controls (n = 25)

 Decidual tissue at time of miscarriage or TOP RT-PCR; IHC Expression of
• Osteopontin ↓
Bao et al. (2012) Prospective case control

  • RM (n = 32)

  • vs

  • controls (n-35)

 Decidual samples at time of miscarriage/TOP PCR; western blot TLR3 expression
• mRNA (median) ↑*
• Protein (ratio:β-actin) ↑*
Fu et al. (2013) Prospective observational

  • RM (n = 25)

  • vs

  • controls (n = 285)

 Decidual samples at time of miscarriage/TOP FC; ELISA • CD27+ NK cells: Th17 cell ratio ↓*
Hosseini et al. (2014) Prospective case control

  • RM (n = 15)

  • vs

  • controls (n = 15)

 Menstrual blood sample on Day 2 of menstruation FC Expression of
• CCR7 ↑
on
CD56+CD16+ and CD56+CD16−
• CD45RO ↓*
on CD56+CD3−
Sotnikova et al. (2014) Prospective case control

  • RM (n = 26)

  • vs

  • Controls (n = 37)

 Decidual samples at time of miscarriage/TOP FC; PCR Expression of:
• CD56+CD161+ ↑*
• CD56+NKG2A+ ↓*
Wang et al. (2014) Prospective case control

  • RM (n = 30)

  • vs

  • Controls (n = 30)

 Decidual samples at time of miscarriage/TOP FC CD56+/CD16−/CD158a+ cells
• KIR2DL1/S1 ↓*
Guo et al. (2017) Prospective case control

  • RM (n = 11)

  • vs

  • controls (n = 12)

 Decidual samples at time of miscarriage/TOP FC, PCR, Matrigel invasion assay, western blot, ELISA Expression of:
• KIR2DL4 ↓*
• NKG2A ↓*
Jiang et al. (2017) Prospective case control

  • RIF (n = 32)

  • vs

  • controls (n = 23)

 Endometrial tissue taken on Day 7–9 post-LH surge IHC Ratio of cells in endometrium:
• CD57+: CD56+ ratio ↑*
Correlation between ratio of
• CD57+ to CD56+ and percentage of NEGATIVE
FoxP3+ in endometrium RM and controls
Huang et al. (2019) Prospective case control

  • RM (n = 49)

  • vs

  • Controls (n = 52)

 Decidual samples at time of miscarriage/TOP qRT-PCR; western blot; ELISA Expression of:
• miR30e ↓*
Li et al. (2019) Prospective case control 15 RM 15 controls Endometrial tissue (RM); decidual tissue at TOP for (controls) FC Expression of
• CD49a ↓
Lu et al. (2020) Prospective case control

  • RM (n = 8)

  • vs

  • controls (n = 45; n = 9 for assay)

 Decidual samples at time of miscarriage/TOP FC Expression of:
• CD82 ↓*
• CD29 ↑*
on CD56dim
Wei et al., (2020) Prospective case control

  • RM (n = 58)

  • vs

  • controls (n = 49)

 Endometrial tissue taken on in mid-luteal phase IHC Correlation of NK cells with:
IDO POSITIVE in
RM and controls
Lyzikova et al. (2020) Prospective case control

  • RM (n = 39)

  • vs

  • controls (n = 63)

 Endometrial samples IHC uNK correlation with:
• FoxP3 Tregs POSITIVE RM and controls*
• PGRMC1 NEGATIVE RM*
POSITIVE controls*
Zhao et al. (2020) Prospective case control

  • RM (n = 30)

  • vs

  • controls (n = 30)

 Endometrial biopsy on day LH surge +7 Multiplex IHC staining Correlation of uNk cell density with:
• CD3+ cell density POSITIVE*

Effect direction in relation to RM/RIF group: ↑increase; ↓decrease; ↔no difference between the groups.

*

P < 0.05.

ERPC, evacuation of retained products of conception; FC, flow cytometry; IHC, immunohistochemistry; RIF, recurrent implantation failure; RM, recurrent miscarriage; STOP, surgical termination of pregnancy; TOP, termination of pregnancy; uRM, unexplained recurrent miscarriage.