Landsberger Martin, Staudt Alexander, Choudhury Sangita, Trimpert Christiane, Herda Lars R, Klingel Karin, Kandolf Reinhard, Schultheiss Heinz-Peter, Kroemer Heyo K, Völker Uwe, Felix Stephan B
Department of Internal Medicine B, Ernst Moritz Arndt University, Greifswald, Germany.
Am Heart J. 2008 Jul;156(1):92-99.e2. doi: 10.1016/j.ahj.2008.02.015. Epub 2008 May 16.
Growing evidence suggests participation of autoimmune mechanisms in the pathogenesis of dilated cardiomyopathy (DCM).
Patients with heart failure (left ventricular ejection fraction < or =50%) due to DCM (n = 98) or ischemic cardiomyopathy (ICM, n = 49) and controls with normal left ventricular function (n = 98) were included. Immunoglobulin G antibodies were purified from plasma by affinity chromatography and analyzed by surface plasmon resonance analysis. We analyzed the distribution of autoantibodies against Kv channel-interacting protein (KChIP) 2.6, cardiac troponin I (cTnI), and the beta1-adrenergic receptor (second extracellular loop, cardiac beta1-adrenergic receptor [SEL-beta1-AR])-two other known autoantibodies involved in heart failure. Effects of antibodies against KChIP2 on cell death of isolated rat cardiomyocytes were assessed by flow cytometry.
We detected autoantibodies against KChIP2.6 in 14.3% (P < .015 vs controls, P = .286 vs ICM) of the DCM samples, in 8.2% of the ICM samples (P = .304 vs controls), and in 4.1% of the control samples. Virus persistence was significantly associated with detection of autoantibodies against KChIP2.6 in DCM patients (P = .025). Antibodies against SEL-beta1-AR were more frequent in DCM samples (34.7%, P < .001 vs controls, P = .02 vs ICM) and ICM samples (16.3%, P = .083 vs control) than in control samples (7.1%). Antibodies against cTnI were more frequent in DCM samples (20.4%, P < .001 vs controls, P = .769 vs ICM) and in ICM samples (18.4%, P < .01 vs controls) than in control samples (4.1%). Antibodies against rat KChIP2 enhanced cell death in isolated rat cardiomyocytes. Immunofluorescence indicated cell surface expression of KChIP2.
Autoantibodies against KChIP2.6, SEL-beta1-AR, and cTnI appear to be associated with DCM. Antibodies against KChIP2 may enhance cell death of rat cardiomyocytes.
越来越多的证据表明自身免疫机制参与扩张型心肌病（DCM）的发病过程。
纳入因DCM（n = 98）或缺血性心肌病（ICM，n = 49）导致心力衰竭（左心室射血分数≤50%）的患者以及左心室功能正常的对照组（n = 98）。通过亲和层析从血浆中纯化免疫球蛋白G抗体，并采用表面等离子体共振分析进行检测。我们分析了抗Kv通道相互作用蛋白（KChIP）2.6、心肌肌钙蛋白I（cTnI）以及β1 - 肾上腺素能受体（第二个细胞外环，心脏β1 - 肾上腺素能受体[SEL - β1 - AR]）的自身抗体分布情况，后两者是另外两种已知的与心力衰竭相关的自身抗体。通过流式细胞术评估抗KChIP2抗体对分离的大鼠心肌细胞死亡的影响。
我们在14.3%的DCM样本中检测到抗KChIP2.6自身抗体（与对照组相比，P <.015；与ICM组相比，P =.286），在8.2%的ICM样本中检测到（与对照组相比，P =.304），在4.1%的对照样本中检测到。病毒持续存在与DCM患者中抗KChIP2.6自身抗体的检测显著相关（P =.025）。抗SEL - β1 - AR抗体在DCM样本（34.7%，与对照组相比，P <.001；与ICM组相比，P =.02）和ICM样本（16.3%，与对照组相比，P =.083）中比在对照样本（7.1%）中更常见。抗cTnI抗体在DCM样本（20.4%，与对照组相比，P <.001；与ICM组相比，P =.769）和ICM样本（18.4%，与对照组相比，P <.01）中比在对照样本（4.1%）中更常见。抗大鼠KChIP2抗体增强了分离的大鼠心肌细胞的死亡。免疫荧光显示KChIP2在细胞表面表达。
抗KChIP2.6、SEL - β1 - AR和cTnI自身抗体似乎与DCM有关。抗KChIP2抗体可能增强大鼠心肌细胞的死亡。
