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Relationship between the cytotoxic activity of peripheral blood natural killer cells and recurrent miscarriage
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  • Yong-Nu Zhang,
  • Chun-Yu Huang,
  • Ruo-Chun Lian,
  • Jian Xu,
  • Yun-Feng Fu,
  • Yong Zeng,
  • Wen-Wei Tu
Yong-Nu Zhang
Shenzhen Zhongshan Urology Hospital
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Chun-Yu Huang
University of Hong Kong
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Ruo-Chun Lian
Shenzhen Zhongshan Urology Hospital
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Jian Xu
Shenzhen Zhongshan Urology Hospital
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Yun-Feng Fu
Shenzhen Zhongshan Urology Hospital
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Yong Zeng
Shenzhen Zhongshan Urology Hospital
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Wen-Wei Tu
University of Hong Kong
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Abstract

Peripheral blood natural killer (pNK) cells can be recruited by the endometrium to participate in the decidualization and be in contact with the villus in the intervillous space during pregnancy. Moreover, pNK cells can exert cytotoxicity to cytotrophoblast, especially in abnormal pregnancy. However, it is still controversial about the association between pNK cytotoxicity and RM so far. In this study, we aim to compare the percentage, immunophenotype and function of pNK cells between patients with RM and fertile controls. The peripheral blood was collected from 49 patients with RM and 11 fertile women in their middle luteal phase of the menstrual cycle. pNK cells were co-cultured with K562 cells at three different cell ratios to measure the cytotoxicity. The percentage of CD3-CD56+ pNK was analyzed by flow cytometry and quantified to evaluate the expression of cytotoxic granules (granzyme B, granulysin, and perforin), and the cell surface receptors related to pNK cell cytotoxicity (NKG2D, NKp30, NKp46, CD158a, CD158b) were also detected. The general linear model analysis showed that pNK cell cytotoxicity in patients with RM was significantly lower than that in fertile controls. The RM group possessed a significantly lower level of granzyme B+ pNK cells and significantly higher level of CD158a+, CD158b+ pNK cells than that in the control group. However, there was no significant difference in the proportion of circulating CD3-CD56+ NK cells expressing the granzyme B, granulysin, perforin, NKG2D, NKp30, NKp46, CD158a, CD158b. Our results suggested that a lower pNK cytotoxicity might be associated with RM.