Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing.
Department of Rheumatology and Immunology, Shanghai Jiaotong University School of Medicine, Ruijin Hospital, Shanghai, China.
Rheumatology (Oxford). 2022 Nov 28;61(12):4962-4974. doi: 10.1093/rheumatology/keac192.
Leucocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of leucocyte receptors. Our previous study reported LILRA3 transcripts were markedly upregulated in neutrophils from patients with APS. We undertook this study to investigate clinical implications of LILRA3 in APS and its potential role in APS-associated thrombosis.
Two independent cohorts were studied. The first consisted of 294 APS patients, 48 asymptomatic aPL carriers and 150 healthy controls (HCs) from Peking University People's Hospital. The second included 99 APS patients, 25 aPL carriers and 40 HCs from United States APS centres. Serum or plasma concentrations of LILRA3 and MPO-DNA complexes were measured. Additionally, 35 patients with thrombotic APS (tAPS) were evaluated to determine potential effects of immunosuppressive therapy on serum concentrations of LILRA3 and MPO-DNA complexes.
Both positivity and serum concentration of LILRA3 were significantly increased in APS patients, especially in those with tAPS. LILRA3-positive tAPS patients displayed more severe thrombotic manifestations. Serum LILRA3 was positively correlated with MPO-DNA complexes in LILRA3-positive tAPS. After immunosuppressive treatment, LILRA3 and MPO-DNA complexes were consistently decreased in tAPS patients. Key findings from the Peking cohort were confirmed in the United States cohort.
Our study provides first evidence that LILRA3 is aberrantly expressed in APS, especially in patients with tAPS. Serum LILRA3 correlated with MPO-DNA complexes, and the two indices were consistently decreased in tAPS patients after treatment. LILRA3 may play a role in thrombosis of APS and may serve as a biomarker and/or therapeutic target in tAPS.
白细胞免疫球蛋白样受体 A3（LILRA3）属于白细胞受体家族。我们之前的研究报告称，APS 患者中性粒细胞中 LILRA3 转录本明显上调。我们进行这项研究旨在探讨 LILRA3 在 APS 中的临床意义及其在 APS 相关血栓形成中的潜在作用。
研究包括两个独立队列。第一队列包括来自北京大学人民医院的 294 例 APS 患者、48 例无症状抗磷脂抗体携带者和 150 例健康对照者（HCs）。第二队列包括来自美国 APS 中心的 99 例 APS 患者、25 例抗磷脂抗体携带者和 40 例 HCs。检测血清或血浆中 LILRA3 和 MPO-DNA 复合物的浓度。此外，对 35 例血栓性 APS（tAPS）患者进行评估，以确定免疫抑制治疗对血清 LILRA3 和 MPO-DNA 复合物浓度的潜在影响。
APS 患者中 LILRA3 的阳性率和血清浓度均显著升高，尤其是在 tAPS 患者中。LILRA3 阳性的 tAPS 患者表现出更严重的血栓形成表现。LILRA3 阳性的 tAPS 患者血清 LILRA3 与 MPO-DNA 复合物呈正相关。经过免疫抑制治疗后，tAPS 患者的 LILRA3 和 MPO-DNA 复合物均持续下降。北京大学人民医院的主要研究结果在美国队列中得到了证实。
本研究首次提供证据表明，LILRA3 在 APS 中异常表达，尤其是在 tAPS 患者中。血清 LILRA3 与 MPO-DNA 复合物相关，且在治疗后 tAPS 患者中两者均持续下降。LILRA3 可能在 APS 的血栓形成中发挥作用，并可能作为 tAPS 的生物标志物和/或治疗靶点。
