Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
Curr Opin Rheumatol. 2012 Sep;24(5):466-72. doi: 10.1097/BOR.0b013e328356226b.
Cardiac manifestations of neonatal lupus include anti-SSA/Ro-SSB/La-mediated conduction system disease and endocardial/myocardial damage resulting in cardiomyopathy. This review will focus on recent data regarding updates on the proposed pathogenesis of disease, morbidity and mortality, and preventive and treatment therapies.
Evidence from animal models suggests that reactivity to the p200 region of the Ro52 protein, as well as antibody targeting of L-type calcium channels may be important in the development of cardiac neonatal lupus. In-vitro studies support a protective role of β-2 glycoprotein 1 (prevents anti-Ro binding to apoptotic cells) and pathologic roles of the urokinase-plasminogen activator/receptor system (leads to activation of TGF-β), and endothelin-1 secretion by macrophages in mediating tissue injury. Genetic studies highlight the fetal major histocompatibility complex in the development of disease, and a multigenerational study demonstrates that mothers of neonatal lupus children accumulate genetic risk factors preferentially from the neonatal lupus child's grandparents. Retrospective studies identify demographic and echocardiographic risk factors for morbidity and mortality and address the role of fluorinated steroids, intravenous immunoglobulin and hydroxychloroquine for prevention and treatment of disease.
Animal studies, in-vitro experiments, genetic analysis and clinical-translational research in cardiac neonatal lupus reveal novel insights and targets for therapy in this often devastating disease.
新生儿狼疮的心脏表现包括抗 SSA/Ro-SSB/La 介导的传导系统疾病和心内膜/心肌损伤导致心肌病。这篇综述将重点介绍关于疾病发病机制、发病率和死亡率、预防和治疗的最新数据。
动物模型的证据表明，对 Ro52 蛋白的 p200 区域的反应性以及针对 L 型钙通道的抗体可能是心脏新生儿狼疮发展的重要因素。体外研究支持 β-2 糖蛋白 1 的保护作用（阻止抗 Ro 与凋亡细胞结合）和尿激酶纤溶酶原激活物/受体系统的病理作用（导致 TGF-β激活），以及巨噬细胞内皮素-1 分泌在介导组织损伤中的作用。遗传研究强调了胎儿主要组织相容性复合体在疾病发展中的作用，一项多代研究表明，新生儿狼疮患儿的母亲优先从新生儿狼疮患儿的祖父母那里积累遗传风险因素。回顾性研究确定了发病率和死亡率的人口统计学和超声心动图危险因素，并探讨了氟皮质类固醇、静脉注射免疫球蛋白和羟氯喹在预防和治疗疾病中的作用。
心脏新生儿狼疮的动物研究、体外实验、遗传分析和临床转化研究揭示了这种经常导致严重后果的疾病的新见解和治疗靶点。
