Soluble LILRA3 is aberrantly expressed in antiphospholipid syndrome (APS) and is a potential marker of thrombotic APS.

Soluble LILRA3 is aberrantly expressed in antiphospholipid syndrome (APS) and is a potential marker of thrombotic APS.
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可溶性 LILRA3 在抗磷脂综合征 (APS) 中异常表达,是血栓性 APS 的潜在标志物。

DOI:
10.1093/rheumatology/keac192
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发表时间:
2022-03
期刊:
Rheumatology (Oxford)
影响因子:
--
通讯作者:
Guo J
Guo J
中科院分区:
其他
文献类型:
--
作者:
Liu H;Li C;Shi H;Guo Y;Tang Y;Chen C;Zhao Z;Hoy CK;Yalavarthi S;Figueroa-Parra G;Duarte-Garcia A;Zuo Y;Li Z;Knight JS;Guo J

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客观化 白细胞免疫球蛋白样受体A3(LILRA3)属于白细胞受体家族。我们以前的研究报告了抗磷脂综合征(APS)患者的中性粒细胞中LILRA3转录显著上调。我们开展了这项研究,以探讨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。 方法 对两个独立的队列进行了研究。第一组为294例APS患者、48例无症状抗磷脂抗体(APL)携带者和150例来自北京大学人民医院的健康对照。第二组包括99名APS患者、25名APL携带者和40名来自美国APS中心的HC。测定血清或血浆中LILRA3和MPO-DNA复合体的浓度。此外,对35例血栓性APS(TAP)患者进行了评估,以确定免疫抑制治疗对血清LILRA3和MPO-DNA复合体浓度的潜在影响。 结果 APS患者LILRA3阳性率和血清LILRA3浓度均显著升高,尤其是TAPs患者。LILRA3阳性的TAPS患者血栓形成更严重。在LILRA3阳性TAP中,血清LILRA3与MPO-DNA复合体呈正相关。经免疫抑制治疗后,TAPS患者的LILRA3和MPO-DNA复合体持续下降。来自北京队列的关键发现在美国队列中得到了证实。 结论 我们的研究首次提供了LILRA3在APS中异常表达的证据,尤其是在患有TAP的患者中。血清LILRA3与MPO-DNA复合体呈正相关,TAPs患者治疗后LILRA3和MPO-DNA复合体持续下降。LILRA3在APS血栓形成中可能起一定作用,可作为TAPs的生物标志物和/或治疗靶点。
OBJECTIVE 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 antiphospholipid syndrome (APS). We undertook this study to investigate clinical implications of LILRA3 in APS and its potential role in APS-associated thrombosis. METHODS Two independent cohorts were studied. The first consisted of 294 APS patients, 48 asymptomatic antiphospholipid antibody (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 centers. 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. RESULTS 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. CONCLUSION 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.