Department of Internal Medicine, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Pace 9, 20122, Milan, Italy.
Eur J Intern Med. 2010 Feb;21(1):25-9. doi: 10.1016/j.ejim.2009.09.011.
Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is successfully used in acute myocardial infarction with ST elevation (STEMI). Reocclusions follow rt-PA treatment in up to 30% of patients within one year. The infusion of rt-PA may induce the production of anti-t-PA antibodies which could interfere with the function of the native t-PA molecule.
In order to detect and characterise anti-t-PA antibodies, plasma samples were collected from 30 STEMI patients (20 treated and 10 not treated with rt-PA) at baseline before rt-PA infusion and then 15, 30, 90 and 180 days after STEMI and from 40 healthy subjects at baseline only. Immunoenzymatic, chromatographic and chromogenic methods were employed.
An increase of anti-t-PA antibodies was observed 15 days (IgM, p=0.0001) and 30 days (IgG, p=0.0001) after rt-PA infusion. Six patients had large increases of anti-t-PA IgG which bound the catalytic domain of t-PA (two cases) or kringle 2 domain (four cases), were of IgG1 or IgG3 subclasses and interacted with the t-PA molecule in fluid phase.
The infusion of rt-PA may induce the production of specific antibodies that bind active sites of t-PA, thus potentially reducing its in vivo function.
重组组织型纤溶酶原激活剂（rt-PA）溶栓成功用于伴有 ST 段抬高的急性心肌梗死（STEMI）。在一年内，多达 30%的患者在 rt-PA 治疗后会再次发生闭塞。rt-PA 的输注可能会诱导产生抗 t-PA 抗体，这些抗体可能会干扰天然 t-PA 分子的功能。
为了检测和描述抗 t-PA 抗体，从 30 名 STEMI 患者（20 名接受 rt-PA 治疗，10 名未接受 rt-PA 治疗）中采集血浆样本，分别在 rt-PA 输注前、STEMI 后 15、30、90 和 180 天采集，以及从 40 名健康受试者中仅在基线时采集。采用免疫酶、色谱和显色方法。
在 rt-PA 输注后 15 天（IgM，p=0.0001）和 30 天（IgG，p=0.0001）观察到抗 t-PA 抗体增加。6 名患者的抗 t-PA IgG 大量增加，这些抗体结合 t-PA 的催化结构域（两种情况）或kringle 2 结构域（四种情况），属于 IgG1 或 IgG3 亚类，并在液相中与 t-PA 分子相互作用。
rt-PA 的输注可能会诱导产生特异性抗体，这些抗体结合 t-PA 的活性位点，从而可能降低其体内功能。
