Impact of common β1-adrenergic receptor polymorphisms on the interaction with agonistic autoantibodies in dilated cardiomyopathy

Bornholz, Beatrice; Hanzen, Birgit; Reinke, Yvonne; Felix, Stephan B.; Boege, Fritz

doi:10.1016/j.ijcard.2016.03.032

Cited by 5 publications

(3 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A variety of mechanisms have been demonstrated by which β 1 AR-Aabs can possibly harm the cardiovascular system [ 49 ]. Current belief holds that the common denominator of cardiotoxicity of β 1 AR-Aabs is the stabilization of an active conformation of the β 1 AR-molecule, entailing a chronic stimulation and/or hyper-sensitization of β 1 -adrenergic signal transduction in the heart [ 50 ] and related target tissues [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against M5-muscarinic and beta1-adrenergic receptors in periodontitis patients

Scherbaum

Heidecke²,

Bunte

et al. 2020

Aging

Self Cite

View full text Add to dashboard Cite

Autoantibodies against muscarinic and beta 1 -adrenergic receptors are considered a potential cause and/or risk factor for chronic heart failure. Association of periodontitis with such autoantibodies and with impaired heart function has been observed in patients exposed to endemic Chagas' disease, which triggers by itself cardiomyopathy and receptor immunization. Here we studied the association between periodontitis, markers of cardiac injury and receptor autoimmunization in periodontitis patients (n = 147) not exposed to Chagas' disease. The autoantibodies were determined by IgG binding to native intact muscarinic and beta 1 -adrenergic receptors or to a cyclic peptide mimicking the disease-relevant conformational autoepitope presented by the active beta 1 -adrenergic receptor. Possible cardiac injury and inflammatory status were judged by serum levels of proBNP/Troponin I and CRP/IL-6, respectively. These parameters were analysed in healthy and periodontally diseased individuals as well as before and after periodontal therapy. Patients with periodontitis had significantly (p < 0.001) higher levels of autoantibodies against M 5 -muscarinic and beta 1 -adrenergic receptors, which further increased following periodontal therapy. Receptor autoantibodies were associated with increased inflammatory status but not with increased markers of cardiac injury. Thus, our data indicate that periodontitis triggers systemic inflammation, which is associated with receptor autoimmunization, and, independently thereof, with cardiac injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Autoantibodies against M5-muscarinic and beta1-adrenergic receptors in periodontitis patients

Scherbaum

Heidecke²,

Bunte

et al. 2020

Aging

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another source of divergence may be a different representation of receptor polymorphisms in the study population. At least for the β 1 AR, it has been demonstrated that certain frequent polymorphisms have a significant influence on binding as well as functional effects of GPCR autoantibodies 59 . Moreover, to our knowledge, in none of the previous studies, measurements of circulating levels of GPCR autoantibodies have been normalized to total IgG.…”

Section: Discussionmentioning

confidence: 94%

“…At least for the β 1 AR, it has been demonstrated that certain frequent polymorphisms have a significant influence on binding as well as functional effects of GPCR autoantibodies. 59 Moreover, to our knowledge, in none of the previous studies, measurements of circulating levels of GPCR autoantibodies have been normalized to total IgG. Consequently, these studies cannot exclude confounding effects of global inflammatory phenomena on the circulating levels of certain GPCR autoantibodies.…”

Section: Discussionmentioning

confidence: 95%

Receptor autoantibodies: Associations with cardiac markers, histology, and function in human non‐ischaemic heart failure

et al. 2023

Self Cite

View full text Add to dashboard Cite

Aims A causal link between non-ischaemic heart failure (HF) and humoral autoimmunity against G-protein-coupled receptors (GPCR) remains unclear except for Chagas' cardiomyopathy. Uncertainty arises from ambiguous reports on incidences of GPCR autoantibodies, spurious correlations of autoantibody levels with disease activity, and lack of standardization and validation of measuring procedures for putatively cardio-pathogenic GPCR autoantibodies. Here, we use validated and certified immune assays presenting native receptors as binding targets. We compared candidate GPCR autoantibody species between HF patients and healthy controls and tested associations of serum autoantibody levels with serological, haemodynamic, metabolic, and functional parameters in HF. Methods Ninety-five non-ischaemic HF patients undergoing transcatheter endomyocardial biopsy and 60 healthy controls were included. GPCR autoantibodies were determined in serum by IgG binding to native receptors or a cyclic peptide (for β1AR autoantibodies). In patients, cardiac function, volumes, and myocardial structural properties were assessed by cardiac magnetic resonance imaging; right heart catheterization served for determination of cardiac haemodynamics; endomyocardial biopsies were used for histological assessment of cardiomyopathy and determination of cardiac mitochondrial oxidative function by high-resolution respirometry. Results Autoantibodies against β 1 adrenergic (β 1 AR ) , M5-muscarinic (M5AR), and angiotensin II type 2 receptors (AT2R) were increased in HF (all P < 0.001). Autoantibodies against α 1 -adrenergic (α 1 AR) and angiotensin II type 1 receptors (AT1R) were decreased in HF (all P < 0.001). Correlation of alterations of GPCR autoantibodies with markers of cardiac or systemic inflammation or cardiac damage, haemodynamics, myocardial histology, or left ventricular inflammation (judged by T2 mapping) were weak, even when corrected for total IgG. β 1 AR autoantibodies were related inversely to markers of left ventricular fibrosis indicated by T1 mapping (r = À0.362, P < 0.05) and global longitudinal strain (r = À0.323, P < 0.05). AT2R autoantibodies were associated with improved myocardial mitochondrial coupling as measured by high-resolution respirometry in myocardial biopsies (r = À0.352, P < 0.05). In insulin-resistant HF patients, AT2R autoantibodies were decreased (r = À.240, P < 0.05), and AT1R autoantibodies were increased (r = 0.212, P < 0.05). Conclusions GPCR autoantibodies are markedly altered in HF. However, they are correlated poorly or even inversely to haemodynamic, metabolic, and functional markers of disease severity, myocardial histology, and myocardial mitochondrial efficiency. These observations do not hint towards a specific cardio-pathogenic role of GPCR autoantibodies and suggest that further investigations are required before specific therapies directed at GPCR autoantibodies can be clinically tested in non-ischaemic HF.

show abstract

β2-adrenergic receptor autoantibodies alleviated myocardial damage induced by β1-adrenergic receptor autoantibodies in heart failure

Cao

Chen

Xiaochun

et al. 2018

Cardiovascular Research

View full text Add to dashboard Cite

show abstract

Impact of common β1-adrenergic receptor polymorphisms on the interaction with agonistic autoantibodies in dilated cardiomyopathy

Cited by 5 publications

References 7 publications

Autoantibodies against M5-muscarinic and beta1-adrenergic receptors in periodontitis patients

Autoantibodies against M5-muscarinic and beta1-adrenergic receptors in periodontitis patients

Receptor autoantibodies: Associations with cardiac markers, histology, and function in human non‐ischaemic heart failure

β2-adrenergic receptor autoantibodies alleviated myocardial damage induced by β1-adrenergic receptor autoantibodies in heart failure

Contact Info

Product

Resources

About