Institut National de la Santé et de la Recherche Médicale Team 1138, Cordelier Research Center, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris; Departments of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris.
Departments of Nephrology, Centre Hospitalier Universitaire de Poitiers; Centre National de Référence Maladies Rares: Amylose AL et Autres Maladies à; Dépôts d'Immunoglobulines Monoclonales; Université de Poitiers, Poitiers.
Am J Kidney Dis. 2022 Sep;80(3):341-352. doi: 10.1053/j.ajkd.2021.12.014. Epub 2022 Feb 22.
RATIONALE & OBJECTIVE: Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy (TMA) with kidney involvement, is a rare condition in patients with monoclonal gammopathy. In the absence of known causes of TMA, the role of complement activation in endothelial injury in patients with monoclonal gammopathy remains unknown and was the focus of this investigation.
Case series.
SETTING & PARTICIPANTS: We studied the 24 patients in the French national registry of HUS between 2000 and 2020 who had monoclonal gammopathy without other causes of secondary TMA. We provide the clinical histories and complement studies of these patients.
Monoclonal gammopathy-associated TMA with kidney involvement is estimated to be 10 times less frequent than adult atypical HUS (aHUS) in the French national registry. It is characterized by severe clinical features, with 17 of 24 patients requiring dialysis at disease onset, and with median renal survival of only 20 months. TMA-mediated extrarenal manifestations, particularly cutaneous and neurological involvement, were common and associated with poor overall prognosis. Complement studies identified low C3, normal C4, and high soluble C5b-9 levels in 33%, 100%, and 77% of tested patients, respectively, indicating a contribution of the alternative and terminal complement pathways in the pathophysiology of the disease. Genetic abnormalities in complement genes known to be associated with aHUS were found in only 3 of 17 (17%) who were tested.
Retrospective study without comparison group; limited number of patients, limited available blood samples.
Within the spectrum of TMA, TMA associated with monoclonal gammopathy represents a distinct subset. Our findings suggest that HUS associated with monoclonal immunoglobulin is a complement-mediated disease akin to aHUS.
溶血尿毒综合征（HUS）是一种伴有肾脏受累的血栓性微血管病（TMA），在单克隆丙种球蛋白病患者中较为少见。在缺乏已知的 TMA 病因的情况下，补体激活在单克隆丙种球蛋白病患者内皮损伤中的作用尚不清楚，这也是本研究的重点。
病例系列。
我们研究了 2000 年至 2020 年期间法国国家 HUS 注册中心的 24 例无其他继发性 TMA 病因的单克隆丙种球蛋白病患者。我们提供了这些患者的临床病史和补体研究资料。
单克隆丙种球蛋白相关性 TMA 伴肾脏受累估计比法国国家登记处的成人非典型 HUS（aHUS）少见 10 倍。其特征为严重的临床特征，24 例患者中有 17 例在发病时需要透析，中位肾脏生存率仅为 20 个月。TMA 介导的肾外表现，特别是皮肤和神经受累，较为常见，且与总体预后不良相关。补体研究发现，在 33%、100%和 77%的检测患者中，分别有低 C3、正常 C4 和高可溶性 C5b-9 水平，提示替代和末端补体途径在疾病发病机制中的作用。在接受检测的 17 例患者中，仅有 3 例（17%）发现与 aHUS 相关的补体基因遗传异常。
回顾性研究无对照组；患者数量有限，可用的血液样本有限。
在 TMA 谱中，与单克隆丙种球蛋白相关的 TMA 代表一个独特的亚群。我们的研究结果表明，与单克隆免疫球蛋白相关的 HUS 是一种补体介导的疾病，类似于 aHUS。
