Complement Factor C4d Is a Common Denominator in Thrombotic Microangiopathy
Complement Factor C4d Is a Common Denominator in Thrombotic Microangiopathy
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DOI：
10.1681/asn.2014050429
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发表时间：
2015-09-01
影响因子：
13.6
通讯作者：
Cohen, Danielle
中科院分区：
文献类型：
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作者：
Chua, Jamie S.;Baelde, Hans J.;Cohen, Danielle
补体激活在血栓性微血管病（TMA）中具有主要作用，血栓性微血管病是一种可在多种临床病症中发生的病症。最近关于终末补体抑制药物的试验结果令人鼓舞，这需要生物标志物来识别可能从这种治疗中受益的患者。本研究的主要目的是确定TMA患者肾脏中补体因子C4d的患病率和定位。次要目的是确定哪些补体途径导致C4d沉积，并确定补体激活是否导致末端补体复合物沉积。我们检查了42个肾切片与组织学证实的TMA从异质性患者组获得。对肾小球、肾小管周围毛细血管和小动脉中C4d、甘露糖结合凝集素、C1 q、IgM和C5 b-9的沉积进行评分。值得注意的是，C4d沉积物存在于88.1%的TMA病例中，并且各种临床状况在肾血管系统的各个隔室内具有不同的染色模式。在90.5%的TMA病例中观察到经典途径激活。C5 b-9沉积物存在于78.6%的TMA病例和39.6%的对照（n=53）中，但染色模式在病例和对照之间不同。总之，C4d是TMA的常见结果，无论基础临床状况如何。此外，C5 b-9存在于> 75%的TMA样品中，表明末端补体抑制剂可能在这些患者中具有有益作用。C4d和C5 b-9应作为疑似补体介导的TMA患者临床检查中可能的诊断生物标志物进行研究。
Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can occur in a variety of clinical conditions. Promising results of recent trials with terminal complement-inhibiting drugs call for biomarkers identifying patients who might benefit from this treatment. The primary aim of this study was to determine the prevalence and localization of complement factor C4d in kidneys of patients with TMA. The secondary aims were to determine which complement pathways lead to C4d deposition and to determine whether complement activation results in deposition of the terminal complement complex. We examined 42 renal sections with histologically confirmed TMA obtained from a heterogeneous patient group. Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d deposits were present in 88.1% of TMA cases, and the various clinical conditions had distinct staining patterns within the various compartments of the renal vasculature. Classical pathway activation was observed in 90.5% of TMA cases. C5b-9 deposits were present in 78.6% of TMA cases and in 39.6% of controls (n=53), but the staining pattern differed between cases and controls. In conclusion, C4d is a common finding in TMA, regardless of the underlying clinical condition. Moreover, C5b-9 was present in > 75% of the TMA samples, suggesting that terminal complement inhibitors may have a beneficial effect in these patients. C4d and C5b-9 should be investigated as possible diagnostic biomarkers in the clinical work-up of patients suspected of having complement-mediated TMA.