Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Hematology/Oncology, South Texas Accelerated Research and Therapeutics (START) Center for Cancer Care, San Antonio, TX; and.
Blood Adv. 2018 Aug 28;2(16):2090-2094. doi: 10.1182/bloodadvances.2018019596.
Complement-mediated thrombotic microangiopathy (CM-TMA) is a clinical disorder driven by the generation of excess complement. It is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) with microvascular thrombosis resulting in systemic organ damage (TMA). One form of CM-TMA, atypical hemolytic uremic syndrome (aHUS), is characterized by pathologic complement activation due to the loss of the natural regulators of the complement system, which results in systemic endothelial and organ damage. Lupus erythematosus is a multisystem immune complex disorder associated with activation of complement, as well as renal failure termed lupus nephritis (LN). A subset of these patients also develop TMA, with progressive life-threatening thrombocytopenia, MAHA, and progressive renal failure similar to aHUS. This subset of patients is poorly responsive to corticosteroids, cyclophosphamide, immunomodulation, and plasma exchange. In this article, we report 11 cases of LN associated with TMA progressing through these therapies, 10 of which were successfully treated with complement inhibition. Complement-regulatory protein mutations, including complement factor H (CFH), factor I, factor B, membrane cofactor/(CD46) and thrombomodulin, and CFH-related 1-3, were identified in 6 of 10 patients tested. One patient had a loss of a renal allograft. Three patients had concurrent antiphospholipid syndrome. Two of the 3 patients had normal D-dimers at this presentation. We believe that this subset of lupus patients, with clinical and pathologic manifestations of aHUS, define a separate entity that we believe should be termed CM-TMA associated with LN.
补体介导的血栓性微血管病（CM-TMA）是一种由补体过度产生驱动的临床疾病。其特征是血小板减少症和微血管性溶血性贫血（MAHA）伴有微血管血栓形成，导致全身器官损伤（TMA）。CM-TMA 的一种形式，即非典型溶血尿毒综合征（aHUS），其特征是由于补体系统天然调节剂的丧失导致病理性补体激活，从而导致全身内皮和器官损伤。红斑狼疮是一种多系统免疫复合物疾病，与补体激活以及称为狼疮肾炎（LN）的肾衰竭有关。这些患者中的一部分也会发生 TMA，表现为进行性危及生命的血小板减少症、MAHA 和进行性肾衰竭，类似于 aHUS。这些患者对皮质类固醇、环磷酰胺、免疫调节和血浆置换的反应较差。在本文中，我们报告了 11 例与 TMA 相关的 LN 病例，这些病例通过这些治疗进展，其中 10 例成功接受了补体抑制治疗。补体调节蛋白突变，包括补体因子 H（CFH）、因子 I、因子 B、膜辅因子蛋白（CD46）和血栓调节蛋白，以及 CFH 相关蛋白 1-3，在 10 例检测患者中的 6 例中得到了鉴定。1 例患者失去了肾脏移植物。3 例患者同时患有抗磷脂综合征。在这组患者中，有 3 例患者中的 2 例在发病时 D-二聚体正常。我们认为，这组具有 aHUS 的临床和病理表现的狼疮患者定义了一种单独的实体，我们认为应该将其命名为与 LN 相关的 CM-TMA。
