Department of Laboratory Medicine, Peking University Third Hospital, Beijing, P R China.
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, P R China.
Immunol Invest. 2022 Feb;51(2):425-437. doi: 10.1080/08820139.2020.1835949. Epub 2020 Oct 26.
Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder with severe life-threatening complications shown during pregnancy. It has been reported that the increase in CD16CD56 natural killer (NK) cells in peripheral blood are risk factors for recurrent miscarriages, but this expression of CD16CD56 NK cells in OAPS patients has not been reported, and the mechanism is not clearly illustrated. In this study, we compared the distributional profiles of different NK cell subsets and the expressions of NK cell-activating receptors in peripheral blood of patients with OAPS and healthy women. Our results showed significantly increased NKG2ANKG2D subset and decreased NKG2ANKG2D subset in CD3 CD16CD56 NK cells, CD3CD16CD56 NK cells and CD56T cells in OAPS patients compared with those in healthy control women. The CD27CD11b subset significantly increased in CD3CD16CD56 NK cells in OAPS patients compared with those in healthy control women. In addition, the NKG2ANKG2D subset in CD3CD16CD56 NK subset in triple positivity was higher than single positivity OAPS patients. At the optimal diagnostic threshold established by ROC analysis, using the cut-off of NKG2ANKG2D and CD27CD11b subset in CD3CD16CD56 NK cells is 10.10% and 92.75%, the sensitivity of NKG2ANKG2D and CD27CD11b to detect patients with OAPS compared with healthy control results was 94.1% and 60.8%, and specificity was 84.2% and 89.5%, respectively, with an area under the curve (AUC) of 0.903 and 0.829, respectively. The NKG2ANKG2D subset in CD3CD16CD56 NK cells was positively correlated with the antiphospholipid antibodies lg anti-aCL IgG, lg anti-aCL IgM, lg anti-aCL IgA, lg anti-β2GP1 IgM and Complement 4(C4), while the CD27CD11b subset in CD3CD16CD56 NK cells was correlated with lg anti-β2GP1 IgG and lg anti-β2GP1 IgA. These results suggested that the NK cytotoxic function enhanced in OAPS patients and unbalanced of NK activating receptors and inhibiting receptors may contribute to the immune pathogenesis of OAPS.
产科抗磷脂综合征（OAPS）是一种自身免疫性疾病，在怀孕期间会出现严重的危及生命的并发症。据报道，外周血中 CD16CD56 自然杀伤（NK）细胞的增加是复发性流产的危险因素，但 OAPS 患者中 CD16CD56 NK 细胞的这种表达尚未报道，其机制也未阐明。在这项研究中，我们比较了 OAPS 患者和健康女性外周血中不同 NK 细胞亚群的分布特征和 NK 细胞激活受体的表达。我们的结果显示，与健康对照组女性相比，OAPS 患者外周血中 CD3-CD16CD56 NK 细胞、CD3CD16CD56 NK 细胞和 CD56T 细胞中的 NKG2ANKG2D 亚群显著增加，而 NKG2ANKG2D 亚群减少。与健康对照组女性相比，OAPS 患者外周血中 CD3CD16CD56 NK 细胞中的 CD27CD11b 亚群显著增加。此外，三重阳性的 CD3CD16CD56 NK 细胞亚群中的 NKG2ANKG2D 亚群高于单阳性 OAPS 患者。在 ROC 分析建立的最佳诊断阈值下，使用 CD3CD16CD56 NK 细胞中 NKG2ANKG2D 和 CD27CD11b 亚群的截断值分别为 10.10%和 92.75%，NKG2ANKG2D 和 CD27CD11b 对检测 OAPS 患者与健康对照组的敏感性分别为 94.1%和 60.8%，特异性分别为 84.2%和 89.5%，曲线下面积（AUC）分别为 0.903 和 0.829。CD3CD16CD56 NK 细胞中的 NKG2ANKG2D 亚群与抗磷脂抗体 lg 抗 aCL IgG、lg 抗 aCL IgM、lg 抗 aCL IgA、lg 抗β2GP1 IgM 和补体 4（C4）呈正相关，而 CD3CD16CD56 NK 细胞中的 CD27CD11b 亚群与 lg 抗β2GP1 IgG 和 lg 抗β2GP1 IgA 呈正相关。这些结果表明，OAPS 患者的 NK 细胞毒性功能增强，NK 激活受体和抑制受体的失衡可能有助于 OAPS 的免疫发病机制。
