Department of Dermatology and Allergy, Hannover Medical School, Comprehensive Allergy Center, Hereditary Angioedema center for rare diseases, Hannover, Germany.
Department of Dermatology, Venerology and Allergology, University Medical Centre Göttingen, Göttingen, Germany.
Allergy. 2022 Mar;77(3):946-955. doi: 10.1111/all.15013. Epub 2021 Jul 28.
The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood.
To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE-inhibitor induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous urticaria (CSU-AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin-lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme-linked immunosorbent assay.
New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast cell-/histamine-mediated CSU-AE. However, FAP-α and tPA were significantly increased in all AE compared to controls. In HAE, FAP- α, tPA, uPAR, pentraxin-3, Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and VE-Cadherin were significantly increased, whereas for Ang-2 the difference was significant compared to CSU-AE only. Tie-2 correlated strongly negatively with C4, C1-INH activity, and C1-INH function.
This study is the first to compare HAE, ACE-AE, and CSU-AE. Although significance is limited by small sample size, Tie-2 was identified as a new promising biomarker candidate for HAE. FAP- α and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 were increased in BK-AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.
血管性水肿（AE）潜在阵发性通透性紊乱的病理生理学尚未完全了解。
为了确定特定 AE 亚型的临床和实验室参数，前瞻性纳入 40 名 AE 患者：15 名遗传性血管性水肿（HAE）、13 名血管紧张素转换酶抑制剂诱导的血管性水肿（ACE-AE）和 12 名慢性自发性荨麻疹中无风团的肥大细胞介导的血管性水肿（CSU-AE）。10 名健康受试者作为对照。通过酶联免疫吸附试验评估指示纤维胶凝素-凝集素途径、内皮细胞激活或血管完整性或炎症受损的标志物的血清水平。
甚至无法确定新的常规临床诊断标准，甚至无法区分缓激肽介导的（BK-）AE（即 HAE 和 ACE-AE）与肥大细胞/组胺介导的 CSU-AE。然而，与对照组相比，所有 AE 患者的 FAP-α 和 tPA 均显着增加。与对照组相比，在 HAE 中，FAP-α、tPA、uPAR、Pentraxin-3、Tie-2、sE-选择素和 VE-钙粘蛋白显着增加。与 CSU-AE 和 ACE-AE 相比，HAE 患者 sE-选择素、Tie-2 和 VE-钙粘蛋白显着增加，而与 CSU-AE 相比，Ang-2 的差异仅显着。Tie-2 与 C4、C1-INH 活性和 C1-INH 功能呈强烈负相关。
这项研究是首次比较 HAE、ACE-AE 和 CSU-AE。尽管由于样本量小，意义有限，但 Tie-2 被确定为 HAE 的一种有前途的新生物标志物候选物。FAP-α 和 tPA 可能作为 AE 的一般标志物，而 sE-选择素和 Ang-2 仅在 BK-AE 中增加。我们的结果为不同 AE 亚型中内皮功能障碍和丝氨酸蛋白酶的作用提供了信息。
