Mikes Bálint, Sinkovits György, Farkas Péter, Csuka Dorottya, Schlammadinger Agota, Rázsó Katalin, Demeter Judit, Domján Gyula, Réti Marienn, Prohászka Zoltán
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
2nd Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
Thromb Res. 2014 Apr;133(4):616-21. doi: 10.1016/j.thromres.2014.01.034. Epub 2014 Feb 1.
Genetic and autoimmune risk factors contribute to the development of thrombotic thrombocytopenic purpura (TTP) but triggers are needed to bring about acute disease. The aim of the study was to investigate the association of neutrophil activation with acute TTP, to assess whether neutrophil activation changes during plasma exchange therapy and to show if complement- and neutrophil activation are parallel, characteristic processes in acute TTP.
Altogether 49 EDTA-plasma samples of 21 TTP patients with acute disease and 17 in remission were investigated along with 20 healthy controls. A stable complex of PMNE-proteinase-inhibitor was measured by ELISA (Calbiochem, Merck-Millipore, Darmstadt, Germany).
Acute disease was associated with significantly increased PMNE levels, the group medians were similarly low in TTP patients in remission and in healthy controls. Increased PMNE levels were characteristic for hematologically active and ADAMTS13 deficient form of TTP. PMNE concentration inversely correlated to disease activity markers platelet count (r=-0.349, p=0.032) and hemoglobin levels (p=-0.382 p=0.018). Achievement of remission was associated with significant reduction of plasma PMNE levels (p=0.031, Wilcoxon test). There was positive correlation between PMNE levels and complement activation markers C3a and Bb.
We report increased PMNE levels in acute TTP and showed its association to activity markers of acute TTP and complement activation. Effective treatment of an acute TTP episode resulted in marked decrease in PMNE levels. Our data support and extend previous observations that neutrophil extracellular traps may be released in acute TTP and potentially contribute to the pathophysiology of this disease.
遗传和自身免疫风险因素促成了血栓性血小板减少性紫癜（TTP）的发病，但引发急性疾病还需要触发因素。本研究的目的是调查中性粒细胞活化与急性TTP的关联，评估血浆置换治疗期间中性粒细胞活化是否发生变化，并表明补体和中性粒细胞活化在急性TTP中是否为平行的特征性过程。
共对21例急性疾病TTP患者、17例缓解期TTP患者的49份乙二胺四乙酸（EDTA）血浆样本以及20名健康对照者的样本进行了研究。通过酶联免疫吸附测定法（ELISA，德国达姆施塔特默克密理博公司旗下的卡尔生物化学公司产品）检测多形核中性粒细胞（PMN）-蛋白酶-抑制剂的稳定复合物。
急性疾病与PMN水平显著升高相关，缓解期TTP患者和健康对照者的组中位数同样较低。PMN水平升高是血液学活跃且缺乏凝血酶原酶解聚素和金属蛋白酶13（ADAMTS13）的TTP形式的特征。PMN浓度与疾病活动标志物血小板计数呈负相关（r=-0.349，p=0.032），与血红蛋白水平呈负相关（p=-0.382，p=0.018）。病情缓解与血浆PMN水平显著降低相关（p=0.031，Wilcoxon检验）。PMN水平与补体活化标志物C3a和Bb呈正相关。
我们报告了急性TTP中PMN水平升高，并表明其与急性TTP的活动标志物及补体活化相关。急性TTP发作的有效治疗导致PMN水平显著下降。我们的数据支持并扩展了先前的观察结果，即急性TTP中可能会释放中性粒细胞胞外陷阱，并可能促成该疾病的病理生理学过程。
