Kobe University Graduate School of Medicine, Kobe, Japan, and Osaka University, Suita, Japan.
University of Toyama, Toyama, Japan.
Arthritis Rheumatol. 2020 Nov;72(11):1882-1891. doi: 10.1002/art.41410. Epub 2020 Sep 30.
The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, β -glycoprotein I (β GPI) complexed with HLA class II molecules (β GPI/HLA-DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the β GPI/HLA II complex as a potential risk factor for RPL in women.
Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti-β GPI antibodies, and lupus anticoagulant as well as anti-β GPI/HLA-DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross-sectional study, women with RPL and their partners underwent HLA-DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti-β GPI/HLA-DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential).
Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti-β GPI/HLA-DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti-β GPI/HLA-DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti-β GPI/HLA-DR antibodies.
The anti-β GPI/HLA-DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.
抗磷脂综合征（APS）的临床表现包括血管血栓形成和妊娠并发症以及复发性妊娠丢失（RPL）。然而，在超过一半的 RPL 患者中，病因从未确定。最近，发现β-糖蛋白 I（β GPI）与 HLA Ⅱ类分子（β GPI/HLA-DR）复合物是 APS 的主要自身抗体靶标。本研究旨在评估抗β GPI/HLA II 复合物自身抗体的血清水平作为女性 RPL 的潜在危险因素。
在 227 例 RPL 妇女中检测了抗磷脂抗体（aPL），包括 IgG/IgM 抗心磷脂抗体、IgG/IgM 抗β GPI 抗体和狼疮抗凝剂以及抗β GPI/HLA-DR 抗体。在这项前瞻性、多中心、横断面研究中，RPL 妇女及其伴侣接受了 HLA-DR 免疫分型和分析，以确定与 RPL 相关的潜在原因和危险因素。使用生育期女性的对照组血清样本确定了抗β GPI/HLA-DR 抗体水平的正常范围（208 例女性）。
在 227 例 RPL 妇女中，检测到 aPL 抗体 19.8%，抗β GPI/HLA-DR 抗体阳性 52（22.9%）。在 227 例妇女中，121 例（53.3%）无 RPL 危险因素，在这些原因不明的 RPL 妇女中，24 例（19.8%）抗β GPI/HLA-DR 抗体阳性。在 112 例有 APS 临床症状但 aPL 水平不符合 APS 诊断标准的妇女中，21 例（18.8%）抗β GPI/HLA-DR 抗体阳性。
抗β GPI/HLA-DR 抗体常与 RPL 相关。检测这些自身抗体有助于了解 RPL 的发病机制。我们的发现可能为治疗产科 APS 患者的 RPL 提供潜在的新治疗策略。
