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Front Biosci (Landmark Ed). 2019 Mar 1;24:1037-1049.

Anti-ß1-Adrenoreceptor auto-Antibodies in elderly heart failure patients.

Author information

1
Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Department of Internal Medicine - Cardiology, Berlin, Germany, and DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany.
2
Experimental and Clinical Research Center, Charite - Universitatsmedizin Berlin, Campus Buch Berlin, Germany.
3
Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Department of Internal Medicine - Cardiology, Berlin, Germany.
4
Universitatsklinikum Schleswig-Holstein, Campus Lubeck, Klinik fur Rheumatologie, Lubeck, Germany.
5
Charite - Universitatsmedizin Berlin, Campus Campus Virchow Klinikum, Department of Nephrology and Intensive Care, Berlin, Germany.
6
HealthTwist GmbH, Biomedizinischer Forschungscampus Berlin-Buch, Germany.
7
CellTrend, Biotechnologiepark, Luckenwalde, Germany, Heidecke@CellTrend.de.
8
CellTrend, Biotechnologiepark, Luckenwalde, Germany.
9
Experimental and Clinical Research Center, Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Berlin, Germany.

Abstract

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.

PMID:
30844728

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