Potential utility of a non-invasive menstrual blood immunophenotype analysis in reproductive medicine.

Kevin Marron, Conor Harrity
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Abstract

Purpose Can a comprehensive flow cytometry panel be used to assess immunophenotype profiles in menstrual blood of patients experiencing reproductive failure and age matched controls of proven fertility? Methods 58 recurrent pregnancy loss and repeated implantation failure patients, along with 15 age matched controls of proven fertility, had menstrual blood samples obtained within the first 24 hours of the onset of menstruation to non-invasively assess the local immunophenotype. Using a comprehensive multi-parameter flow panel the lymphocyte sub-populations were described and compared. Results Relative to well established peripheral blood immunophenotyping values, distinct lymphocyte population differences were noted between the subgroups. The ratios of CD4+ and CD8+ T-cells were inverted relative to peripheral blood and uterine NK cells represented by CD56bright were distinctly visualised, emphasising the distinction of menstrual and peripheral blood. Relative to controls there were marked increases in CD3+ve T-cells (p=0.009), CD4:CD8 ratio (p=0.004), CD19 B-cells (p=0.026) and CD56dim NK's (p=0.002) in the reproductive failure cases. Conclusions Flow cytometric evaluation can provide a rapid and objective analysis of lymphocyte subpopulations in many forms of tissue and fluid. The findings show significant variations in cellular composition of immune cells indicating a distinct compartment, with differences between cases and controls. Immunological assessment of the menstrual blood immunophenotype, in clinically appropriate patients, may provide insight into the aetiology of adverse reproductive outcome, without the risks and inconveniences associated with a more invasive endometrial biopsy.

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无创经血免疫表型分析在生殖医学中的潜在用途。
目的 能否使用全面的流式细胞仪面板来评估生殖失败患者和经证实有生育能力的年龄匹配对照组月经血中的免疫表型特征?方法 58 名反复妊娠失败和反复植入失败的患者以及 15 名经证实有生育能力的年龄匹配对照者在月经来潮的头 24 小时内采集月经血样本,以非侵入性方式评估局部免疫表型。利用全面的多参数血流面板对淋巴细胞亚群进行了描述和比较。结果 与公认的外周血免疫分型值相比,各亚组之间的淋巴细胞群存在明显差异。与外周血相比,CD4+和CD8+ T细胞的比例倒置,以CD56bright为代表的子宫NK细胞明显可见,突出了月经血和外周血的区别。与对照组相比,生殖系统衰竭病例中的 CD3+ve T 细胞(p=0.009)、CD4:CD8 比率(p=0.004)、CD19 B 细胞(p=0.026)和 CD56dim NK 细胞(p=0.002)明显增加。结论 流式细胞仪评估可对多种组织和液体中的淋巴细胞亚群进行快速、客观的分析。研究结果表明,免疫细胞的细胞组成存在明显差异,表明存在不同的区系,病例与对照组之间也存在差异。在临床上,对合适患者的经血免疫表型进行免疫学评估,可深入了解不良生殖结果的病因,而无需进行更具侵袭性的子宫内膜活检所带来的风险和不便。
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