高龄复发性流产患者体液免疫异常的单中心研究 Translated title: Humoral Immunity Abnormalities in Advanced Maternal-Age Women With Recurrent Spontaneous Abortion: A Single Center Study

Abstract

目的

探讨高龄复发性流产（recurrent spontaneous abortion, RSA）患者体液免疫状态。

方法

采用回顾性研究方法，纳入2022年1月–2023年10月在本中心就诊的RSA患者，检测其多种自身抗体，采用多因素logistic回归方法，在控制体质量指数（body mass index, BMI）、既往活产史、自然流产次数三个混杂因素的基础上，比较不同年龄分组（低龄组20～34岁，高龄组35～45岁）与多种自身抗体之间的关联，进而探讨高龄RSA女性与低龄RSA女性体液免疫状态差异。

结果

共纳入4008例RSA女性，其中高龄组1158例，低龄组2851例。高龄组和低龄组抗磷脂综合征、系统性红斑狼疮、干燥综合征、类风湿性关节炎、未分化结缔组织病的患病率分别为15.6%和14.1%、0.0%和0.1%、0.9%和0.9%、0.3%和0.0%、23.7%和22.6%，两组比较差异无统计学意义。高龄组和低龄组抗磷脂抗体（antiphospholipid antibodies, aPLs）阳性率分别为19.1%和19.5%，抗核抗体（antinuclear antibody, ANA）阳性率分别为6.6%和6.6%，抗可提取核抗原（extractable nuclear antigen, ENA）抗体阳性率分别为9.2%和10.5%，抗双链DNA（anti-double stranded DNA, dsDNA）抗体阳性率分别为2.0%和2.0%，抗单链DNA（anti-single-stranded DNA, ssDNA）抗体阳性率分别为2.2%和1.2%，抗α-胞衬蛋白抗体（antibodies against alpha-fodrin, AAA）阳性率分别为5.1%和4.9%，甲状腺自身免疫（thyroid autoimmunity, TAI）分别为17.8%和16.8%，两组比较差异均无统计学意义，高龄组中狼疮抗凝物（lupus anticoagulant, LA）阳性率为1.6%，低龄组为2.7%，差异有统计学意义（校正的优势比=0.36，95%置信区间：0.17～0.78）。4008例RSA患者中aPLs谱中三种抗体累计阳性778例，其中抗β2糖蛋白Ⅰ抗体（anti-β2 glycoprotein Ⅰ antibodies, β2GPⅠ Ab）-IgG/IgM阳性者520例，aCL-IgG/IgM阳性者58例，LA阳性者73例，β2GPⅠ Ab-IgG/IgM与aCL-IgG/IgM同时阳性者105例，β2GPⅠ Ab-IgG/IgM与LA同时阳性者17例，aCL-IgG/IgM与LA同时阳性者2例，三种抗体均阳性者3例。

结论

本研究未发现高龄RSA患者与低龄RSA患者体液免疫状态存在差异。

Translated abstract

Objective

To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA).

Methods

A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women.

Result

A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-β2 glycoprotein Ⅰ antibodies (β2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both β2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both β2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies.

Conclusion

Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.