Mapping the antigenic regions of streptokinase in humans before and after streptokinase therapy.
Mapping the antigenic regions of streptokinase in humans before and after streptokinase therapy.
复制标题
绘制链激酶治疗前后人体链激酶抗原区域的图谱。
DOI：
10.1016/0161-5890(95)00041-c
复制
发表时间：
1995
影响因子：
3.6
通讯作者：
Reed,GL
中科院分区：
文献类型：
--
作者：
Parhami-Seren,B;Lynch,M;White,HD;Reed,GL
链激酶可挽救心肌梗死患者的生命。然而，由于几乎所有接受测试的人都显示出针对链激酶的抗体，因此对链激酶的过敏反应很常见，而且可能很严重。在这份报告中，我们分析了从正常献血者和患者中纯化的抗体，链激酶治疗前后，以确定链激酶分子的抗原区域。在所有受试者中均观察到链激酶抗体，但个体间抗体滴度存在20-30倍差异。这些滴度的个体差异在SK治疗后持续存在，尽管所有患者的滴度在链激酶治疗后1周平均上升7倍。为了确定抗体结合的链激酶区域，我们采用了一组特征良好的鼠单克隆抗体和重组链激酶截短片段。抗体链激酶的三个离散区域可以检测到在所有患者。抗体的其他两个区域，在氨基末端和羧基末端的分子，被发现在许多，但不是在所有的患者。然而，链激酶第六区的抗体是罕见的，滴度非常低。有趣的是，接受链激酶治疗的个体在治疗后往往表现出与链激酶治疗前相同的免疫反应性模式。我们的结论是，虽然存在个体差异的链激酶抗体的滴度，链激酶的某些区域似乎更具抗原性或免疫显性。
Streptokinase saves lives in patients suffering a myocardial infarction. However, because nearly all humans tested show antibodies against streptokinase, allergic reactions to streptokinase are common and may be severe. In this report we have analysed antibodies purified from normal blood donors and patients, before and after streptokinase therapy, to identify antigenic regions of the streptokinase molecule. Antibody to streptokinase was seen in all subjects, but there were 20–30-fold differences between individuals in the antibody titer. These individual differences in titer persisted after SK treatment, though the titer for all patients rose an average of 7-fold 1 week after streptokinase therapy. To identify the regions of streptokinase to which the antibody bound, we employed a panel of well-characterized murine monoclonal antibodies and recombinant streptokinase truncated fragments. Antibodies to three discrete regions of streptokinase could be detected in all patients. Antibodies to two other regions, at the amino terminal and carboxyl terminus of the molecule, were found in many but not in all patients. However, antibodies to a sixth region of streptokinase were uncommon and of very low titer. Interestingly, individuals receiving streptokinase tended to show the same pattern of immunoreactivity after treatment as they had prior to streptokinase. We conclude that although individual differences exist in the titers of streptokinase antibody, certain regions of streptokinase appear to be more antigenic or immunodominant.