Matsuyama Tomomi, Kuwana Masataka, Matsumoto Masanori, Isonishi Ayami, Inokuma Shigeko, Fujimura Yoshihiro
Department of Blood Transfusion Medicine, Nara Medical University, Shijyo-cho 840, Kashihara city, Nara, 634-8522, Japan.
Thromb Haemost. 2009 Aug;102(2):371-8. doi: 10.1160/TH08-12-0825.
To clarify the pathogenic processes of thrombotic microangiopathies (TMAs) in patients with connective tissue disease (CTD), we analysed clinical characteristics and plasma ADAMTS13 levels in 127 patients with CTD-TMAs, including patients with systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis (RA), and 64 patients with acquired idiopathic thrombotic thrombocytopenic purpura (ai-TTP). Plasma levels of ADAMTS13 activity, antigen, and inhibitors were determined by enzyme immunoassays. IgG type anti-ADAMTS13 antibodies were also detected by immunoblots using purified ADAMTS13. ADAMTS13 activity was significantly decreased in CTD-TMAs, regardless of the underlying disease, but the frequency of severe deficiency (defined as <0.5% of normal) was lower in CTD-TMA patients than in ai-TTP patients (16.5% vs. 70.3%, p < 0.01). Severe deficiency of ADAMTS13 activity was predominantly detected in patients with RA- and SLE-TMAs, and was closely associated with the presence of anti-ADAMTS13 IgG antibodies. CTD-TMA patients with severe deficiency of ADAMTS13 activity appeared to have lower platelet counts and better therapeutic outcomes. At least two phenotypic TMAs occur in patients with CTDs: a minor population with deficient ADAMTS13 activity caused by neutralising autoantibodies, and a major population with normal or moderately reduced activity. Classifying CTD-TMAs by ADAMTS13 activity may be useful in predicting the clinical course and therapeutic outcomes, as patients with moderately reduced activity are likely to have more prominent renal impairment and poor prognoses.
为阐明结缔组织病（CTD）患者血栓性微血管病（TMA）的致病过程，我们分析了127例CTD-TMA患者的临床特征和血浆ADAMTS13水平，这些患者包括系统性红斑狼疮（SLE）、系统性硬化症、多发性肌炎/皮肌炎和类风湿关节炎（RA）患者，以及64例获得性特发性血栓性血小板减少性紫癜（ai-TTP）患者。采用酶免疫分析法测定血浆中ADAMTS13活性、抗原和抑制剂水平。还使用纯化的ADAMTS13通过免疫印迹法检测IgG型抗ADAMTS13抗体。无论潜在疾病如何，CTD-TMA患者的ADAMTS13活性均显著降低，但CTD-TMA患者严重缺乏（定义为低于正常水平的0.5%）的频率低于ai-TTP患者（16.5%对70.3%，p<0.01）。ADAMTS13活性严重缺乏主要在RA-和SLE-TMA患者中检测到，并且与抗ADAMTS13 IgG抗体的存在密切相关。ADAMTS13活性严重缺乏的CTD-TMA患者似乎血小板计数较低且治疗效果较好。CTD患者中至少出现两种表型TMA：一小部分是由中和性自身抗体导致ADAMTS13活性缺乏的患者，而大部分是活性正常或中度降低的患者。根据ADAMTS13活性对CTD-TMA进行分类可能有助于预测临床病程和治疗效果，因为活性中度降低的患者可能有更明显的肾功能损害和不良预后。
