Haberland Annekathrin, Holtzhauer Martin, Schlichtiger Alice, Bartel Sabine, Schimke Ingolf, Müller Johannes, Dandel Michael, Luppa Peter B, Wallukat Gerd
Medical Chemistry and Pathobiochemistry, Charité- Universitätsmedizin Berlin, Germany.
Human Gesellschaft für Biochemie und Diagnostica mbH, Magdeburg, Germany.
Eur J Pharmacol. 2016 Oct 15;789:37-45. doi: 10.1016/j.ejphar.2016.06.061. Epub 2016 Jul 1.
The effect of autoantibodies on G-protein coupled receptors in the pathogenesis of diseases, especially of the heart and vascular system, is an increasingly accepted fact today. Dilated cardiomyopathy (DCM) is the most intensively investigated pathological situation of these. With DCM, autoantibodies against the β1-adrenoceptor and the muscarinic M2-receptor have been found in high percentage of investigated patients. Immunoadsorption for autoantibody removal has already shown a long-term beneficial therapeutic effect, but has remained limited in its application because of the complexity of this method. A new easy applicable treatment strategy has, therefore, been discovered. Because of intra- and inter-loop epitope variability of the β1-adrenoceptor specific autoantibodies and also the occurrence of further autoantibodies of this class such as the ones against the β2- and α1-adrenoceptor, the ETA-, proteinase activated-, and the AT1-receptors in different pathological situations, this newly discovered broad-spectrum neutralizer of all these autoantibodies - aptamer BC 007 - is under development. The binding and neutralizing effect was investigated applying a bioassay of spontaneously beating neonatal rat cardiomyocytes and enzyme-linked immunosorbent assay (ELISA) - technology. The usefulness of aptamer BC 007 to specify column technology for the removal of serum autoantibodies was also demonstrated. The presented data suggest that aptamer BC 007 might be an appropriate molecule candidate to support future research about the meaning of G-protein-coupled receptor autoantibodies.
自身抗体对疾病，尤其是心脏和血管系统疾病发病机制中G蛋白偶联受体的影响，如今已成为一个越来越被认可的事实。扩张型心肌病（DCM）是其中研究最为深入的病理情况。在DCM患者中，已发现高比例的患者存在针对β1肾上腺素能受体和毒蕈碱M2受体的自身抗体。通过免疫吸附去除自身抗体已显示出长期有益的治疗效果，但由于该方法的复杂性，其应用仍然有限。因此，人们发现了一种新的易于应用的治疗策略。由于β1肾上腺素能受体特异性自身抗体的环内和环间表位变异性，以及在不同病理情况下此类其他自身抗体的出现，如针对β2和α1肾上腺素能受体、ETA、蛋白酶激活和AT1受体的自身抗体，这种新发现的能中和所有这些自身抗体的广谱中和剂——适配体BC 007正在研发中。应用新生大鼠自发搏动心肌细胞生物测定法和酶联免疫吸附测定（ELISA）技术研究了其结合和中和作用。还证明了适配体BC 007用于血清自身抗体去除的特异性柱技术的有效性。所呈现的数据表明，适配体BC 007可能是一个合适的分子候选物，有助于未来关于G蛋白偶联受体自身抗体意义的研究。
