Department of Internal Medicine III, University of Heidelberg, Germany.
Circ Res. 2012 Jan 6;110(1):145-58. doi: 10.1161/CIRCRESAHA.111.243360.
Human heart failure is a disease with multifactorial causes, considerable morbidity, and high mortality. Several circulating autoantibodies, some of them being heart-specific, play a crucial role in the progression and induction of heart failure. However the precise mechanisms on how these autoantibodies perpetuate or even induce an organ specific autoimmune response are not yet fully understood. Also it is being a matter of current research to elucidate a potential pathophysiological role of the innate immune system in generating auto-reactive antibodies. In this review we will summarize the current available literature on circulating autoantibodies which are related to human heart failure. We will present clinical and animal studies that demonstrate the occurrence and pathophysiological relevance of several autoantibodies in heart failure, as well as point out biological mechanisms on molecular and cellular level. Finally the beneficial therapeutic effects of numerous clinical studies that target the humoral arm of the immune system by using either intravenous immunoglobulins and/or immunoadsorption will be critically discussed.
人类心力衰竭是一种多因素引起的疾病,发病率相当高,死亡率也很高。几种循环自身抗体,其中一些是心脏特异性的,在心力衰竭的进展和诱导中起着至关重要的作用。然而,这些自身抗体如何持续存在甚至诱导器官特异性自身免疫反应的确切机制尚不完全清楚。目前的研究还旨在阐明先天免疫系统在产生自身反应性抗体方面的潜在病理生理作用。在这篇综述中,我们将总结与人类心力衰竭相关的循环自身抗体的现有文献。我们将介绍临床和动物研究,这些研究表明了几种自身抗体在心力衰竭中的发生和病理生理学相关性,并指出了分子和细胞水平上的生物学机制。最后,我们将批判性地讨论许多针对免疫球蛋白系统体液臂的临床研究的有益治疗效果,这些研究使用静脉注射免疫球蛋白和/或免疫吸附来实现。