Department of Rheumatology and Immunology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangzhou, China.
Am J Reprod Immunol. 2024 Nov;92(5):e13940. doi: 10.1111/aji.13940.
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs.
The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared.
The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6% vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4% vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance.
The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs.
抗磷脂综合征（APS）是一种自身免疫性疾病，其特征是血栓形成事件和不良妊娠结局，常伴有抗磷脂抗体（aPL）升高。2023 年 ACR/EULAR APS 标准需要持续的中高滴度 aPL 来进行实验室确认。然而，低滴度 aPL 复发性流产（RM）患者的影响仍存在争议。本研究旨在分析治疗对低滴度 aPLs RM 患者妊娠结局和母婴并发症的影响。
本研究纳入了 2018 年 1 月至 2022 年 7 月在广州医科大学附属第三医院进行 aPLs 检测的 237 例 RM 患者的 252 例妊娠。患者根据 aPLs 滴度分为两组：86 例低滴度 aPLs（92 例妊娠）和 151 例 aPLs 阴性（160 例妊娠）。低滴度组中，71 例接受治疗，21 例未接受治疗，而所有 aPLs 阴性患者均未接受治疗。71 例低滴度 aPLs 治疗患者分为两组。A 组（n=15）接受标准治疗方案，包括低剂量阿司匹林（LDA）和低分子肝素（LMWH）。相比之下，B 组（n=56）接受多药物治疗方案，除了标准的 LDA 和 LMWH 治疗外，还包括羟氯喹（HCQ）和/或糖皮质激素（GC）和/或静脉注射免疫球蛋白（IVIG）。随后比较了两组的妊娠结局和母婴并发症。
未治疗的低滴度 aPLs 组中 aCL-IgM 的阳性率最高（76.2%），其次是 aβ2GPI-IgM（23.8%）和 LA（5.6%）。未治疗的低滴度 aPLs 组中单一抗体阳性率为 90.5%，双抗体阳性率为 9.5%，而治疗的低滴度 aPLs 组中相应的阳性率分别为 87.3%和 12.7%。未检测到三抗体阳性。未治疗的低滴度 aPLs 组的既往流产次数更多（p<0.05），抗核抗体（ANA）阳性率更高（p<0.05）。此外，与 aPLs 阴性组相比，治疗的低滴度 aPLs 组的补体水平更低。与 aPLs 阴性组相比，未治疗和治疗的低滴度 aPLs 组的免疫球蛋白 IgM 水平均升高（p<0.05）。治疗后，低滴度组的活产率显著高于未治疗组（67.6% vs. 33.3%；p=0.005）。与 aPLs 阴性组相比，未治疗的低滴度患者的流产率明显更低（32.4% vs. 66.7%；p=0.005）。两组间母婴并发症无显著差异。在标准治疗组（A 组）中，有 8 例（53.3%）活产，而多药物治疗组（B 组）有 40 例（71.4%）活产，明显高于标准治疗组，但差异无统计学意义。
本研究表明，与 aPLs 阴性 RM 组相比，未经治疗的低滴度阳性 aPLs RM 患者的流产复发率更高。然而，适当干预后复发显著减少，表明低滴度 aPLs RM 患者治疗的益处。
