Mandle R, Baron C, Roux E, Sundel R, Gelfand J, Aulak K, Davis A E, Rosen F S, Bing D H
Center for Blood Research, Harvard Medical School, Boston, MA 02115.
J Immunol. 1994 May 1;152(9):4680-5.
An autoantibody that we hypothesize to react with the reactive center of the plasma serine proteinase inhibitor, C1 inhibitor (C1INH), has been found in a patient with acquired C1INH deficiency. The Ab blocks the ability of C1INH to inhibit the hydrolysis of N-carbobenzyloxy-L-lysine thiobenzylester by purified C1s. A cryoprecipitate from the patient's plasma as well as the Ig fraction were able to block C1INH inhibition of C1s. The immunoaffinity purified Ab to C1INH from the patient's plasma Ig fraction neutralizes the inhibitory activity of C1INH in a dose-dependent manner and blocks the ability of normal C1INH to form a complex with C1s. The neutralizing activity of the purified Ab is reversed by a synthetic peptide that corresponds to the amino acid sequence in the P1 to P15 positions of the reactive center of C1INH but not by a 34-amino-acid trypsin peptide or 37-amino-acid elastase peptide derived from the C-terminus of C1INH. Western blot analysis indicated that the Ab is an oligoclonal Ig with kappa light chains.
在一名获得性C1抑制因子（C1INH）缺乏症患者体内发现了一种自身抗体，我们推测该抗体与血浆丝氨酸蛋白酶抑制剂C1抑制因子（C1INH）的反应中心发生反应。该抗体可阻断C1INH抑制纯化的C1s对N - 苄氧羰基 - L - 赖氨酸硫代苄酯水解的能力。患者血浆的冷沉淀物以及免疫球蛋白部分均能够阻断C1INH对C1s的抑制作用。从患者血浆免疫球蛋白部分通过免疫亲和纯化得到的抗C1INH抗体以剂量依赖方式中和C1INH的抑制活性，并阻断正常C1INH与C1s形成复合物的能力。纯化抗体的中和活性可被一种合成肽逆转，该合成肽对应于C1INH反应中心P1至P15位置的氨基酸序列，但不能被源自C1INH C末端的34个氨基酸的胰蛋白酶肽或37个氨基酸的弹性蛋白酶肽逆转。蛋白质印迹分析表明，该抗体是一种具有κ轻链的寡克隆免疫球蛋白。
