未孕的复发性流产患者抗甲状腺抗体与外周血淋巴细胞亚群之间关系的研究

Study of the relationship between antithyroid antibody and peripheral blood lymphocyte subsets in nonpregnant women with recurrent spontaneous abortion

目的 探讨抗甲状腺抗体(ATA)阳性的复发性流产(RSA)患者未孕时的细胞免疫状态,及其发病机制。 方法 选择2015年12月—2016年12月期间就诊于盛京医院门诊的未孕RSA患者200例进行回顾性病例对照研究,根据ATA水平及甲状腺功能状态将其分组:ATA阳性86例,记为ATA^+组,其中促甲状腺激素(TSH)≥2.50 mIU/L 36例,记为ATA^+ high组,TSH<2.50 mIU/L 50例,记为ATA^+ normal组;ATA阴性114例,记为ATA^-组,其中TSH≥2.50 mIU/L 50例,记为ATA^- high组,TSH<2.50 mIU/L 64例,记为ATA^- normal组。比较各组之间各淋巴细胞亚群的差异。 结果 ① ATA^+ high组CD16^+CD56^+自然杀伤(NK)细胞增高的发生率(80.6%,29/36)高于ATA^+ normal组(42.0%,21/50),差异有统计学意义(P=0.001),CD3^+CD4^+辅助性T(Th)细胞降低的发生率(41.7%,15/36)高于ATA^+ normal组(18.0%,9/50),差异有统计学意义(P=0.016);②ATA^+ high组CD16^+CD56^+NK细胞增高的发生率(80.6%,29/36)高于ATA^- high组(54.00%,27/50),差异有统计学意义(P=0.011);CD3^+CD4^+Th细胞降低的发生率(41.7%,15/36)高于ATA^- high组(20.0%,10/50),差异有统计学意义(P=0.029);③ATA^+组与ATA^-组比较,ATA^+ normal组与ATA^- normal组比较,ATA^- high组与ATA^- normal组比较,各淋巴细胞亚群异常(增高/降低)的发生率差异均无统计学意义(P值均>0.05)。 结论 ATA阳性与轻度甲状腺功能受损同时存在时,未孕的RSA患者细胞免疫状态存在异常,推测ATA阳性合并轻度甲状腺功能受损时,RSA的发生可能与免疫异常有关。

Objective To find if anti-thyroid antibody (ATA) can be related with cellular immune status in unpregnant patients with recurrent spontaneous abortion (RSA), and its pathogenesis. Methods A total of 200 patients with RSA who were treated in Shengjing Hospital of China Medical Uuiversity from December 2015 to December 2016 were enrolled for retrospective case-control study. According to the state of thyroid function, the patients were divided into two parts: ATA positive group (86 cases, ATA^+ group), 36 cases of which thyroid stimulating hormone (TSH)≥2.50 mIU/L, recording as ATA^+ high group, 50 cases of which TSH<2.50 mIU/L recording as ATA^+ normal group;ATA negative group (114 cases, ATA^- group), 50 cases of which TSH≥2.50 mIU/L recording as ATA^- high group, 64 cases of which TSH<2.50 mIU/L recording as ATA^- normal group. The lymphocyte subsets and the thyroid function of each group were detected and the differences of lymphocyte subsets were analyzed between the groups. Results 1) The incidence of increased CD16^+CD56^+ natural killer (NK) cells of ATA^+ high group (80.6%, 29/36) was significantly higher than that in ATA^+ normal group (42.0%, 21/50) (P=0.001). The incidence of decreased CD3^+CD4^+ helper T (Th) cells of ATA^+ high group (41.7%, 15/36) was significantly higher than that in ATA^+ normal group (18.0%, 9/50) (P=0.016). 2) The incidence of increased CD16^+CD56^+ NK cells of ATA^+ high group (80.6%, 29/36) was significantly higher than ATA^- high group (54.00%, 27/50) (P=0.011). The incidence of decreased CD3^+CD4^+Th cells of ATA^+ high group (41.7%, 15/36) was significantly higher than that in ATA^-high group (20.0%, 10/50) (P=0.029). 3) Compared ATA^+ group with ATA^- group, ATA^+ normal group with ATA^- normal group, ATA^- high group with ATA^- normal group, there was no significant difference in the incidence of lymphocyte subsets abnormality (increase/decrease) (P>0.05). Conclusion Abnormal status of cellular immune status exists in RSA patients with both ATA and mild thyroid abnormalities, suggesting that the occurrence of RSA may be associated with immune factors when ATA and mild thyroid abnormalities coexist.