NK cell frequency and cytotoxicity in correlation to pregnancy outcome and response to IVIG therapy among women with recurrent pregnancy loss

J Cell Physiol. 2019 Jun;234(6):9428-9437. doi: 10.1002/jcp.27627. Epub 2018 Oct 14.


Background: Recurrent miscarriage (RM) has a multifactorial etiology mainly due to chromosomal abnormalities and immunological factors. Treating RM has remained to be a challenging issue and the role of intravenous immunoglobulin (IVIG) in treating RM is still controversial.

Materials and methods: This study aimed to evaluate the changes in natural killer (NK) cells' frequency and cytotoxicity in patients with RM who received the IVIG therapy. A total of 78 women with a history of three or more recurrent miscarriages were included and their peripheral blood was drawn in case of positive pregnancy test. On the same date, 400 mg/kg of IVIG was administrated intravenously in 38 women and it continued every four weeks through weeks 30-32 of gestation. The remaining 40 patients with RM were included to be the untreated control group. Then, the effects of IVIG on NK cell frequency, cytotoxic activity, and the expression of inhibitory and activating receptors in the patients with RM, pre and posttreatment were assessed.

Results: NK cells percentage and cytotoxicity were significantly reduced in the IVIG-treated patients after 32 weeks of gestation (p < 0.0001). Expression levels of inhibitory receptors was increased, however, the expression levels of activating receptors were significantly decreased after the IVIG therapy. Pregnancy outcome after the treatment was significantly higher (86.8%) in the IVIG-treated patients than controls (45%; p = 0.0006).

Conclusion: Our results suggested that women with RM may benefit from IVIG as a therapeutic approach and the frequency and functional status of peripheral NK cells may serve as a valuable predictive factor of therapy response.

Keywords: IVIG therapy; NK cell; live birth; recurrent miscarriage; recurrent pregnancy loss (RPL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / genetics
  • Adult
  • Cell Count
  • Cytotoxicity, Immunologic*
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Pregnancy
  • Pregnancy Outcome
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Immunoglobulins, Intravenous
  • RNA, Messenger