Ji Ruoyu, Xu Yijing, Zhi Yuxiang
Department of Allergy, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Orphanet J Rare Dis. 2025 May 26;20(1):251. doi: 10.1186/s13023-025-03776-3.
Hereditary angioedema (HAE) is a rare inherited disease characterized by recurrent, potentially life-threatening angioedema. The vascular endothelium dysfunction is reported to play a role in angioedema episodes. Here, we conducted a case-control study to explore the correlation between vascular endothelium growth factor (VEGF), a representative indicator for endothelium dysfunction, and HAE as well as its attack frequency, disease control and disease severity.
Patients with HAE and non-hereditary angioedema in their attack-free period were prospectively recruited. Demographic and disease information were collected through questionnaires. Disease control of HAE was assessed with the angioedema control test (AECT) with a recall period of three months. The current severity of HAE was comprehensively assessed through frequency of angioedema episodes, occurrence of life-threatening angioedema, necessity for hospitalization or emergency department visits. The plasma VEGF level was measured by chemiluminescence microparticle immunoassay. We compared clinical characteristics between HAE and non-hereditary angioedema patients, as well as among HAE patients with different attack frequency, disease control and disease severity. We further performed several generalized linear models (GLMs) to examine the correlation between VEGF levels and the attack frequency, disease control and disease severity of HAE.
We enrolled 74 patients with HAE and 55 patients with non-hereditary angioedema. HAE patients exhibited higher VEGF levels in remission than controls (112 vs. 60 ng/ml, P < 0.001). VEGF levels further increased in HAE patients with more frequent angioedema attacks, poorer disease control and greater disease severity. Results of GLMs confirmed significant correlations between plasma VEGF concentrations and the attack frequency of angioedema, disease control status and disease severity of HAE.
Circulating VEGF level elevated in patients with HAE during attack-free periods, particularly among those with greater disease burden, suggesting the involvement of vascular endothelial dysfunction in the pathogenesis of HAE. VEGF may serve as a predictive biomarker for risk stratification and disease monitoring in HAE.
遗传性血管性水肿（HAE）是一种罕见的遗传性疾病，其特征为反复发作且可能危及生命的血管性水肿。据报道，血管内皮功能障碍在血管性水肿发作中起作用。在此，我们进行了一项病例对照研究，以探讨内皮功能障碍的代表性指标血管内皮生长因子（VEGF）与HAE及其发作频率、疾病控制情况和疾病严重程度之间的相关性。
前瞻性招募处于无发作期的HAE患者和非遗传性血管性水肿患者。通过问卷收集人口统计学和疾病信息。采用血管性水肿控制测试（AECT）评估HAE的疾病控制情况，回顾期为三个月。通过血管性水肿发作频率、危及生命的血管性水肿的发生情况、住院或急诊就诊的必要性，综合评估HAE的当前严重程度。采用化学发光微粒子免疫分析法测定血浆VEGF水平。我们比较了HAE患者与非遗传性血管性水肿患者之间的临床特征，以及不同发作频率、疾病控制情况和疾病严重程度的HAE患者之间的临床特征。我们进一步进行了几个广义线性模型（GLM），以检验VEGF水平与HAE的发作频率、疾病控制情况和疾病严重程度之间的相关性。
我们纳入了74例HAE患者和55例非遗传性血管性水肿患者。HAE患者缓解期的VEGF水平高于对照组（112 vs. 60 ng/ml，P < 0.001）。血管性水肿发作更频繁、疾病控制更差且疾病严重程度更高的HAE患者，其VEGF水平进一步升高。GLM的结果证实血浆VEGF浓度与血管性水肿的发作频率、HAE的疾病控制状态和疾病严重程度之间存在显著相关性。
HAE患者在无发作期循环VEGF水平升高，尤其是在疾病负担较重的患者中，这表明血管内皮功能障碍参与了HAE的发病机制。VEGF可能作为HAE风险分层和疾病监测的预测生物标志物。
