Baxter Innovations GmbH, Wagramer Strasse, Vienna, Austria.
J Thromb Haemost. 2011 May;9(5):936-44. doi: 10.1111/j.1538-7836.2011.04224.x.
Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non-inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently replenish the deficient enzyme.
To explore the use of recombinant ADAMTS13 (rADAMTS13) as a potential therapeutic agent in acquired TTP, we investigated its efficacy in normalizing VWF-cleaving activity in the presence of ADAMTS13 inhibitors.
Thirty-six plasma samples from TTP patients were adjusted to predefined inhibitor titers, and recovery of ADAMTS13 activity was analyzed following supplementation with rADAMTS13.
We showed a linear relation between the inhibitor titer measured and effective rADAMTS13 concentration necessary for reconstitution of VWF-cleaving activity in the presence of neutralizing autoantibodies.
Our results support the further investigation of the potential therapeutic applicability of rADAMTS13 as an adjunctive therapy in acquired TTP.
获得性血栓性血小板减少性紫癜（TTP）中观察到的 von Willebrand 因子（VWF）-切割蛋白酶 ADAMTS13 严重缺乏是由针对该蛋白酶的抑制性和非抑制性自身抗体引起的。目前的血浆置换治疗被认为可以去除循环中的抗体，并同时补充缺乏的酶。
为了探索重组 ADAMTS13（rADAMTS13）作为获得性 TTP 潜在治疗剂的用途，我们研究了其在存在 ADAMTS13 抑制剂的情况下使 VWF 切割活性正常化的疗效。
将 36 份来自 TTP 患者的血浆样品调整至预设的抑制剂滴度，并在补充 rADAMTS13 后分析 ADAMTS13 活性的恢复情况。
我们表明，在存在中和性自身抗体的情况下，测量的抑制剂滴度与恢复 VWF 切割活性所需的有效 rADAMTS13 浓度之间存在线性关系。
我们的结果支持进一步研究 rADAMTS13 在获得性 TTP 中的辅助治疗应用的潜在治疗适用性。
