The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction
The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction
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DOI：
10.1111/j.1365-2141.2008.07074.x
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发表时间：
2008-05-01
影响因子：
6.5
通讯作者：
Mackie, I. J.
中科院分区：
文献类型：
--
作者：
Austin, S. K.;Starke, R. D.;Mackie, I. J.
抗ADAMTS13自身抗体在血栓性血小板减少性紫癜(TTP)的微血栓形成中起重要作用。在严重的抗磷脂综合征(APS)病例中，微血栓的发生与TTP相似，提示可能存在相互致病因素。然而，ADAMTS13在APS中的作用尚不清楚。我们假设ADAMTS13基因的异常可能发生在APS中，并评估了68例抗磷脂抗体(APA)患者的ADAMTS13和von Willebrand因子(VWF)，其中包括52例APS患者。33例(49%)患者有抗ADAMTS13的免疫球蛋白抗体，其中12例患者的ADAMTS13活性降低，表明存在中和抗体。ADAMTS13活性低(中位数34%)的有22/68(33%)，所有ADAMTS13抗原水平正常与功能障碍的ADAMTS13一致。ADAMTS13活性降低并不继发于von Willebrand因子(VWF)升高或VWF分泌增加(正常的VWF前肽)，尽管在APS中发现VWF清除减少。分析发现，ADAMTS13异常与任何APA特征或血栓形成/产科并发症之间没有关联，尽管这项研究没有足够的动力来解决临床关联。然而，这些发现突显了ADAMTS13自身抗体和ADAMTS13功能障碍可在APS中发生，尽管其临床意义尚不确定，但ADAMTS13功能障碍可能在TTP以外的自身免疫性疾病中参与血栓形成。
Autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I motif, member 13) play an important role in the development of microthrombosis in thrombotic thrombocytopenic purpura (TTP). In severe cases of antiphospholipid syndrome (APS), microthrombosis can occur similar to that seen in TTP, suggesting possible mutual pathogenic factors. However, the role of ADAMTS13 in APS is unknown. We hypothesised that aberrations in ADAMTS13 may occur in APS and evaluated ADAMTS13 and von Willebrand factor (VWF) in 68 patients with antiphospholipid antibodies (aPA) including 52 with APS. Thirty-three (49%) had IgG anti-ADAMTS13 with 12 of these patients having reduced ADAMTS13 activity, suggesting neutralising antibodies. Low ADAMTS13 activity (median 34%) was demonstrated in 22/68 (33%), all with normal ADAMTS13 antigen levels consistent with dysfunctional ADAMTS13. Reduced ADAMTS13 activity was not secondary to elevated von Willebrand factor (VWF), or increased VWF secretion (normal VWF propeptide), although a reduced VWF clearance was noted in APS. Analysis found no associations between the ADAMTS13 abnormalities and any aPA profile or thrombotic/obstetric complications, although this study was not adequately powered to address clinical associations. Nevertheless, these findings highlight that ADAMTS13 autoantibodies and ADAMTS13 dysfunction can occur in APS, and although the clinical significance remains undetermined, ADAMTS13 dysfunction may be contributory to thrombogenesis in autoimmune conditions other than TTP.