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Systemic Characterization of Novel Immune Cell Phenotypes in Recurrent Pregnancy Loss.

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 (T_PH) cells were more abundant in the NPW group than in the NP and RPL groups. Moreover, the percentage of Vδ2⁺PD-1⁺ gamma-delta (γδ) T cells was extremely high, above the 95^th percentile limit, in the NP group compared with the NPW and RPL groups, which has never been reported before. In addition, we also determined the 5^th percentile lower limit and 95^th 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.

SUBMITTER: Liu H

PROVIDER: S-EPMC8195235 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study questionWhat is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature?Summary answerThe guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized.What is known alreadyA previous guideline for the investigation and medical treatment of recurrent miscarriage was published in 2006 and is in need of an update.Study design size durationThe guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 31 March 2017 and written in English were included. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes.Participants/materials setting methodsBased on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.Main results and the role of chanceThe guideline provides 38 recommendations on risk factors, prevention and investigations in couples with RPL, and 39 recommendations on treatments. These include 60 evidence-based recommendations - of which 31 were formulated as strong recommendations and 29 as conditional - and 17 good practice points. The evidence supporting investigations and treatment of couples with RPL is limited and of moderate quality. Of the evidence-based recommendations, only 10 (16.3%) were supported by moderate quality evidence. The remaining recommendations were supported by low (35 recommendations: 57.4%), or very low quality evidence (16 recommendations: 26.2%). There were no recommendations based on high quality evidence. Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions investigations and treatments that should not be used for couples with RPL.Limitations reasons for cautionSeveral investigations and treatments are offered to couples with RPL, but most of them are not well studied. For most of these investigations and treatments, a recommendation against the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.Wider implications of the findingsThe guideline provides clinicians with clear advice on best practice in RPL, based on the best evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. One of the most important consequences of the limited evidence is the absence of evidence for a definition of RPL.Study funding/competing interestsThe guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. J.E. reports position funding from CARE Fertility. S.L. reports position funding from SpermComet Ltd. S.M. reports research grants, consulting and speaker's fees from GSK, BMS/Pfizer, Sanquin, Aspen, Bayer and Daiichi Sankyo. S.Q. reports speaker's fees from Ferring. The other authors report no conflicts of interest.ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

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Systemic Characterization of Novel Immune Cell Phenotypes in Recurrent Pregnancy Loss.

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