Alsenz J, Bork K, Loos M
N Engl J Med. 1987 May 28;316(22):1360-6. doi: 10.1056/NEJM198705283162202.
During the past 25 years, three forms of deficiency of the inhibitor of the first component of complement (C1 inhibitor) with angioedema have been recognized; two forms are hereditary and one is acquired. As compared with hereditary angioedema, the syndrome of acquired C1-inhibitor deficiency is rare, and it is usually associated with lymphoproliferative diseases. We report another type of acquired C1-inhibitor deficiency with angioedema. Two patients with recurrent angioedema but no associated diseases were found to have IgG1 autoantibodies against C1 inhibitor. The anti-C1-inhibitor antibodies prevented binding of C1 inhibitor to activated C1s. Both patients had 60 to 70 percent of normal levels of C1 inhibitor, but it was functionally inactive, with a molecular weight of 96,000 (normal C1 inhibitor, 105,000). In vitro studies of the patients' serum revealed degradation of 125I-labeled 105,000-dalton C1 inhibitor into the inactive 96,000-dalton molecule, caused by activated C1s and not found in normal human serum. We conclude that these cases of acquired C1-inhibitor deficiency resulted from a blockade of C1-inhibitor function by the anti-C1-inhibitor antibodies and from subsequent inactivation of C1 inhibitor by the now uncontrolled enzyme, activated C1s. As in other forms of C1-inhibitor deficiency, the unopposed activation of the complement system led to angioedema.
在过去25年中，已认识到三种伴有血管性水肿的补体第一成分抑制剂（C1抑制剂）缺乏形式；两种为遗传性，一种为获得性。与遗传性血管性水肿相比，获得性C1抑制剂缺乏综合征较为罕见，且通常与淋巴增生性疾病相关。我们报告了另一例伴有血管性水肿的获得性C1抑制剂缺乏类型。两名复发性血管性水肿但无相关疾病的患者被发现存在针对C1抑制剂的IgG1自身抗体。抗C1抑制剂抗体阻止了C1抑制剂与活化的C1s结合。两名患者的C1抑制剂水平均为正常水平的60%至70%，但其功能失活，分子量为96,000（正常C1抑制剂为105,000）。对患者血清的体外研究显示，125I标记的105,000道尔顿C1抑制剂被活化的C1s降解为无活性的96,000道尔顿分子，而在正常人血清中未发现这种情况。我们得出结论，这些获得性C1抑制剂缺乏病例是由抗C1抑制剂抗体对C1抑制剂功能的阻断以及随后由失控的酶活化的C1s导致的C1抑制剂失活所致。与其他形式的C1抑制剂缺乏一样，补体系统的无对抗激活导致了血管性水肿。
