Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Department of Internal Medicine - Cardiology, Berlin, Germany, and DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany.
Experimental and Clinical Research Center, Charite - Universitatsmedizin Berlin, Campus Buch Berlin, Germany.
Front Biosci (Landmark Ed). 2019 Mar 1;24(6):1037-1049. doi: 10.2741/4766.
An autoimmune reaction directed against the cardiac b1-adrenergic receptor (beta1-ADR) leading to the generation of autoantibodies (AA) against this G-coupled receptor has been described in patients with heart failure (HF). Agonist-like beta1-ADR-AA are associated with morbidity in HF patients and even predict mortality. Standardised and valid diagnostic tools to detect beta 1-ADR-AA in clinical routine are lacking. We used a novel ELISA approach to investigate beta 1-ADR-AA in a cohort of 574 HF patients of the CIBIS-ELD trial with follow up. The CIBIS-ELD trial compared the titration of bisoprolol and carvedilol to recommended target doses in regard to BB tolerability in patients aged 65 years and older. Patient with left ventricular (LV) ejection fraction (EF) less than 50% or LV diameter end diastolic (DED) more than 55 cm showed significantly higher levels of beta1-ADR-AA. Although not yet fully validated, this ELISA allowed for a negative correlation of beta1-ADR-AA with the EF at baseline and at the follow up, beta1-ADR-AA further correlated positively with basal heart rate at follow up 12 weeks later. beta1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (pless than 0.01). Changes in beta1-ADR-AA between F-Up and baseline were significantly higher in patients who used beta blockers (p=0.016) before study inclusion. The type of beta-blocker titrated in this study did not affect log beta1-ADR-AA levels at baseline (p=0.132), follow-up (p=0.058), nor the change (p=0.426). beta1-ADR-AA levels were estimated using a novel, commercially available ELISA. Although not yet fully validated, this ELISA allowed for pathophysiological insights: beta1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (pless than 0.01), irrespective of type of BB. Higher levels of beta1-ADR-AA at baseline are associated with higher heart rates, lower ejection fraction and enlarged left ventricles. The relevance of the beta1-ADR-AA biomarker should be further evaluated.
自身免疫反应针对心脏 b1-肾上腺素能受体 (β1-ADR)，导致针对这种 G 蛋白偶联受体的自身抗体 (AA) 的产生，已在心力衰竭 (HF) 患者中描述。激动剂样β1-ADR-AA 与 HF 患者的发病率相关，甚至可以预测死亡率。缺乏用于在临床常规中检测β1-ADR-AA 的标准化和有效的诊断工具。我们使用了一种新的 ELISA 方法来研究 CIBIS-ELD 试验中的 574 名 HF 患者队列中的β1-ADR-AA，并进行了随访。CIBIS-ELD 试验比较了比索洛尔和卡维地洛在 65 岁及以上患者中滴定至推荐目标剂量时的 BB 耐受性。左心室 (LV) 射血分数 (EF) 小于 50%或 LV 直径舒张末期 (DED) 大于 55 cm 的患者β1-ADR-AA 水平显著升高。尽管尚未完全验证，但这种 ELISA 允许β1-ADR-AA 与基线和随访时的 EF 呈负相关，β1-ADR-AA 进一步与 12 周后随访时的基础心率呈正相关。β1-ADR-AA 水平在使用β-受体阻滞剂滴定时下显著升高 (p 小于 0.01)。与基线相比，在研究纳入前使用β受体阻滞剂的患者 (p=0.016)，F-Up 和基线之间的β1-ADR-AA 变化显著更高。在本研究中滴定的β受体阻滞剂的类型在基线时不影响 logβ1-ADR-AA 水平 (p=0.132)，随访时 (p=0.058)，也不影响变化 (p=0.426)。使用一种新的、商业上可获得的 ELISA 来估计β1-ADR-AA 水平。尽管尚未完全验证，但这种 ELISA 允许进行病理生理学研究：β1-ADR-AA 水平在使用β受体阻滞剂滴定时下显著升高 (p 小于 0.01)，与 BB 类型无关。较高的基线β1-ADR-AA 水平与较高的心率、较低的射血分数和左心室增大相关。β1-ADR-AA 生物标志物的相关性应进一步评估。
