Jackson J, Sim R B, Whaley K, Feighery C
Department of Immunology, St. James Hospital, Dublin, Ireland.
J Clin Invest. 1989 Feb;83(2):698-707. doi: 10.1172/JCI113934.
C1-inhibitor (C1-Inh) is an important inhibitor of the inflammatory response and deficiency of this inhibitor, which may be hereditary or acquired, is associated with recurrent episodes of edema. Recently, an autoimmune form of angioedema has been described that is associated with functional deficiency of C1-Inh and an autoantibody that impedes C1-Inh function. In this report we describe the isolation of C1-Inh from the monocytes and plasma of a patient with autoimmune angioedema and demonstrate that the patient's monocytes secrete structurally and functionally normal C1-Inh, but show that this protein circulates in the patient's plasma in an inactive, structurally altered form. Furthermore, using analytic gel electrophoresis techniques it is demonstrated that the patient's autoantibody facilitates cleavage of normal C1-Inh, by its target proteases, to the same species of C1-Inh that is found circulating in the patient's plasma. This autoantibody facilitated cleavage of normal C1-Inh is apparently a consequence of destabilization of protease/inhibitor complexes. These findings contribute to our understanding of protease/C1-Inh interactions and document important observations on pathogenic mechanisms in autoimmune disease.
C1抑制剂（C1-Inh）是炎症反应的一种重要抑制剂，该抑制剂的缺乏（可能是遗传性的或后天获得的）与反复出现的水肿发作有关。最近，已描述了一种自身免疫性血管性水肿，它与C1-Inh的功能缺陷以及一种阻碍C1-Inh功能的自身抗体有关。在本报告中，我们描述了从一名自身免疫性血管性水肿患者的单核细胞和血浆中分离出C1-Inh的过程，并证明该患者的单核细胞分泌结构和功能正常的C1-Inh，但表明这种蛋白质在患者血浆中以无活性的、结构改变的形式循环。此外，使用分析凝胶电泳技术证明，患者的自身抗体通过其靶蛋白酶促进正常C1-Inh裂解为在患者血浆中循环的同一种C1-Inh。这种自身抗体促进的正常C1-Inh裂解显然是蛋白酶/抑制剂复合物不稳定的结果。这些发现有助于我们理解蛋白酶/C1-Inh相互作用，并记录了自身免疫性疾病致病机制的重要观察结果。
