Abstract

Recurrent pregnancy loss (RPL) is a disturbing disease in women, and 50% of RPL is reported to be associated with immune dysfunction. Most previous studies of RPL focused mainly on the relationship between RPL and either T cells or natural killer (NK) cells in peripheral blood and the decidua; few studies presented the systemic profiles of the peripheral immune cell subsets in RPL women. Herein, we simultaneously detected 63 immune cell phenotypes in the peripheral blood from nonpregnant women (NPW), women with a history of normal pregnancy (NP) and women with a history of RPL (RPL) by multi-parameter flow cytometry. The results demonstrated that the percentages of naïve CD4+ T cells, central memory CD4+ T cells, naïve CD8+ T cells, mature NK cells, Vδ1+ T cells and the ratio of Vδ1+ T cells/Vδ2+ T cells were significantly higher in the RPL group than those in the NPW and NP groups, whereas the percentages of terminal differentiated CD4+ T cells, effective memory CD4+ T cells, immature NK cells and Vδ2+ T cells were significantly lower in the RPL group than those in the NPW and NP groups. Interestingly, we found that peripheral T helper (TPH) cells were more abundant in the NPW group than in the NP and RPL groups. In addition, we also determined the 5th percentile lower limit and 95th percentile upper limit of the significantly changed immunological parameters based on the files of the NPW group. Taken together, this is the first study to simultaneously characterize the multiple immune cell subsets in the peripheral blood at a relatively large scale in RPL, which might provide a global readout of the immune status for clinicians to identify clinically-relevant immune disorders and guide them to make clear and individualized advice and treatment plans.

Highlights

  • Recurrent pregnancy loss (RPL) is defined as two or more fetal losses and affects approximately 1% - 2% of reproductive women and < 5% of couples [1, 2]

  • The results showed that there were no significant differences in the percentages of Th1 (CD3+CD4+CXCR5-CXCR3+CCR4+), Th2 (CD3+CD4+CXCR5-CXCR3-CCR4+), Th17 (CD3+ CD4+ CXCR5-CXCR3-CCR4-CCR6+) and Treg cells (CD3+CD4+ CD25+CD127-) (Figures S1Aa–d) among 3 groups, indicating that these immune cell subsets might be not related to RPL in a large population

  • Prior studies primarily focused on the assessment of single or selected peripheral immune cell subsets in RPL, which lacks the simultaneous and comprehensive evaluation of immunological profiles in women of childbearing age

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Summary

Introduction

Recurrent pregnancy loss (RPL) is defined as two or more fetal losses and affects approximately 1% - 2% of reproductive women and < 5% of couples [1, 2]. A recent study by Han et al [11] determined the dynamic alterations of over 370 immune cell features (including cell distribution and functional responses) in maternal blood of normal pregnancy and preeclampsia (PE) by using a high-dimensional mass cytometry immunoassay. They found differentially dynamics of maternal immune system between healthy and preeclamptic pregnancies, suggesting that the determination of the peripheral immune states might lay the groundwork for identifying clinically-relevant immune disorders in women with pathological pregnancy

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