Objectives The antiphospholipid syndrome is defined by antiphospholipid antibodies (aPL) together with arterial and/or venous thromboembolism and/or obstetric morbidities. aPL are overrepresented in systemic lupus erythematosus (SLE) and acute myocardial infarction, but it is unknown whether aPL are associated with calcific aortic valve stenosis (CAVS) in the general population. The prevalence of aPL and other SLE-associated autoantibodies and their impact on aortic valve transcriptomics were therefore determined. Methods 233 tricuspid CAVS cases (median age 74, 69% male) and an age- and sex-matched control population were included. aPL were measured as anti-cardiolipin and anti-β2Glycoprotein-I of IgG/M/A isotypes. Resilient, thickened, and calcified aortic valve (AV) tissue derived from 5 aPL positive and 5 matched aPL negative CAVS patients undergoing surgical aortic valve replacement were analysed by microarrays. Results The prevalence of positivity for any aPL (IgG/M/A) in patients with CAVS was 6.4% (95% CI 3.6% - 10.4%: n = 233). aPL IgG was significantly more prevalent in CAVS cases vs controls (4.6% vs 0.6%, p= 0.04). AV tissue from aPL IgG/IgM positive patients was negatively enriched in pathways related to interferon signalling. 100 differentially expressed genes could predict local AV CAVS progression with supervised machine learning algorithms. Conclusions aPL IgG was more common in CAVS patients compared with matched controls and aPL positivity was associated with altered AV transcriptomics related to local disease progression and interferon pathways. Further studies should aim to establish aPL as a possible risk marker and/or causal factor for CAVS and could offer new precision therapeutic targets.

中文翻译：

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钙化性主动脉瓣狭窄患者的抗磷脂抗体

目的 抗磷脂综合征的定义是抗磷脂抗体 (aPL) 以及动脉和/或静脉血栓栓塞和/或产科疾病。aPL 在系统性红斑狼疮 (SLE) 和急性心肌梗死中的比例过高，但尚不清楚 aPL 是否与一般人群中的钙化性主动脉瓣狭窄 (CAVS) 相关。因此确定了 aPL 和其他 SLE 相关自身抗体的流行及其对主动脉瓣转录组学的影响。方法 纳入 233 例三尖瓣 CAVS 病例（中位年龄 74 岁，69% 为男性）和年龄和性别匹配的对照人群。aPL 被测量为 IgG/M/A 同种型的抗心磷脂和抗 β2 糖蛋白-I。有弹性，加厚，和钙化的主动脉瓣 (AV) 组织来源于 5 名 aPL 阳性和 5 名匹配的 aPL 阴性 CAVS 患者，这些患者接受外科主动脉瓣置换术，通过微阵列分析。结果 CAVS 患者中任何 aPL (IgG/M/A) 的阳性率为 6.4%（95% CI 3.6% - 10.4%：n = 233）。与对照组相比，aPL IgG 在 CAVS 病例中更为普遍（4.6% 对 0.6%，p=0.04）。来自 aPL IgG/IgM 阳性患者的 AV 组织在与干扰素信号传导相关的通路中呈负富集。100 个差异表达的基因可以通过监督机器学习算法预测局部 AV CAVS 进展。结论 与匹配的对照组相比，aPL IgG 在 CAVS 患者中更常见，aPL 阳性与局部疾病进展和干扰素通路相关的 AV 转录组学改变有关。