Mutations in Factor XII, plasminogen gene, angiopoietin-1 gene and kininogen 1 gene have been found in some patients with hereditary angioedema with normal C1 inhibitor (HAE-nl-C1inh), but the underlying disease mechanisms remain unclear. Additionally, there are no accepted biomarkers for this disease. Because the contact system has been implicated in hereditary angioedema with C1 inhibitor deficiency (HAE-C1inh), we studied the fragmentation patterns of serum glycoprotein 120 (sgp120), a protein that is highly susceptible to cleavage by kallikrein, in 31 HAE-C1inh and 13 HAE-nl-C1inh patient plasma samples. Compared to normal controls, the majority of plasma samples from patients with HAE-C1inh contained fragmented sgp120. These samples also showed increased kallikrein amidolytic activity indicating spontaneous contact system activation. In contrast, most samples from HAE-nl-C1inh patients exhibited intact sgp120. However, if these samples were incubated at 4 °C in plastic, significant sgp120 fragmentation and spontaneous contact system activation were observed. Concurrently, there was C1 inhibitor fragmentation that generated the nonfunctional 94 kD fragment and a reduction in C1 inhibitor function. Normal samples did not show sgp120 or C1 inhibitor fragmentation after incubation. We sequenced sgp120 and found it to be identical to inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). These results suggest that sgp120 or ITIH4 is cleaved when the contact system is activated and that this cleavage could be used as a biomarker in patients with HAE-nl-C1inh.

中文翻译：

---

sgp120和遗传性血管性水肿的接触系统：具有正常C1抑制剂的HAE诊断工具。

在某些具有正常C1抑制剂（HAE-n1-C1inh）的遗传性血管性水肿患者中，发现了XII因子，纤溶酶原基因，血管生成素-1基因和激肽原1基因的突变，但尚不清楚其潜在的发病机制。此外，尚无该疾病的生物标志物。由于接触系统已经牵涉到具有C1抑制剂缺乏症（HAE-C1inh）的遗传性血管性水肿，因此我们在31 HAE-C1inh和31中研究了血清糖蛋白120（sgp120）的片段化模式，该蛋白对激肽释放酶的裂解高度敏感。 13个HAE-nl-C1inh患者血浆样品。与正常对照相比，HAE-C1inh患者的大部分血浆样品中含有片段化的sgp120。这些样品还显示激肽释放酶的酰胺分解活性增加，表明自发接触系统激活。相反，大多数来自HAE-n1-C1inh患者的样品均显示完整的sgp120。但是，如果将这些样品在4°C的塑料中孵育，则会观察到明显的sgp120断裂和自发接触系统活化。同时，存在C1抑制剂片段化，产生了非功能性的94 kD片段，并降低了C1抑制剂的功能。孵育后，正常样品未显示sgp120或C1抑制剂断裂。我们对sgp120进行了测序，发现它与α-胰蛋白酶抑制剂重链4（ITIH4）相同。这些结果表明，激活接触系统后，sgp120或ITIH4会被切割，这种切割可以用作HAE-n1-C1inh患者的生物标志物。如果将这些样品在4°C的塑料中孵育，则会观察到明显的sgp120断裂和自发接触系统活化。同时，存在C1抑制剂片段化，产生了非功能性的94 kD片段，并降低了C1抑制剂的功能。孵育后，正常样品未显示sgp120或C1抑制剂断裂。我们对sgp120进行了测序，发现它与α-胰蛋白酶抑制剂重链4（ITIH4）相同。这些结果表明，激活接触系统后，sgp120或ITIH4会被切割，这种切割可以用作HAE-n1-C1inh患者的生物标志物。如果将这些样品在4°C的塑料中孵育，则会观察到明显的sgp120断裂和自发接触系统活化。同时，存在C1抑制剂片段化，产生了非功能性的94 kD片段，并降低了C1抑制剂的功能。孵育后，正常样品未显示sgp120或C1抑制剂断裂。我们对sgp120进行了测序，发现它与α-胰蛋白酶抑制剂重链4（ITIH4）相同。这些结果表明，激活接触系统后，sgp120或ITIH4会被切割，这种切割可以用作HAE-n1-C1inh患者的生物标志物。有C1抑制剂片段化，产生了无功能的94 kD片段，并降低了C1抑制剂功能。孵育后，正常样品未显示sgp120或C1抑制剂断裂。我们对sgp120进行了测序，发现它与α-胰蛋白酶抑制剂重链4（ITIH4）相同。这些结果表明，激活接触系统后，sgp120或ITIH4会被切割，这种切割可以用作HAE-n1-C1inh患者的生物标志物。有C1抑制剂片段化，产生了无功能的94 kD片段，C1抑制剂功能降低。孵育后，正常样品未显示sgp120或C1抑制剂断裂。我们对sgp120进行了测序，发现它与α-胰蛋白酶抑制剂重链4（ITIH4）相同。这些结果表明，激活接触系统后，sgp120或ITIH4会被切割，这种切割可以用作HAE-n1-C1inh患者的生物标志物。