Compensatory Upregulation of Anti-Beta-Adrenergic Receptor Antibody Levels Might Prevent Heart Failure Presentation in Pediatric Myocarditis

Seidel, Franziska; Scheibenbogen, Carmen; Heidecke, Harald; Opgen‐Rhein, Bernd; Pickardt, Thomas; Klingel, Karin; Berger, Felix; Messroghli, Daniel; Schubert, Stephan

doi:10.3389/fped.2022.881208

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…The lack of that compensatory mechanism in PACVS would be potentiated by concomitant increases in IL-6 and IL-8 promoting thrombosis via other pathways [45]. Similar protective functions have been described for β-adrenergic receptor antibodies in pediatric cardiomyopathy [46] and allergic asthma [47].…”

Section: Putative Pathogenic Role Of Blunted Receptor Antibody Adapta...mentioning

confidence: 66%

Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers

Semmler,

Mundorf,

Kuechler

et al. 2023

Vaccines

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SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dysautonomia tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2 vaccination of healthy controls (N = 89; 71 females; mean/median age: 39/49 years) were compared with corresponding values of PACVS-affected persons (N = 191; 159 females; mean/median age: 40/39 years) exhibiting chronic fatigue/dysautonomia (≥three symptoms for ≥five months after the last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases in 11 receptor antibodies (by 25–50%, p < 0.0001), increases in two receptor antibodies (by 15–25%, p < 0.0001) and normal IL-6. In PACVS, serological vaccination–response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p < 0.0001) by increased Angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/mL, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/mL, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/mL, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers.

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Section: Putative Pathogenic Role Of Blunted Receptor Antibody Adapta...mentioning

confidence: 66%

Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers

Semmler,

Mundorf,

Kuechler

et al. 2023

Vaccines

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarities were found in the proteomic searches (Figure 1) and in the targets of autoimmunity observed in human patients (summarized in Table 9) that could not be tested for cross-reactivity here due to the limited availability of sufficient protein at affordable costs. These additional protein targets, which have been documented in both pre-COVID autoimmune cardiomyopathies and in COVID-19 autoimmune cardiopathies, included angiotensin converting enzyme 2 (ACE2) [51,[98][99][100], antineutrophil cytoplasmic antibodies (ANCA) [101][102][103], alpha enolase [104], alpha-and beta-adrenergic receptors [42,[105][106][107][108][109], laminins [110], phospholipids [111][112][113], tropomyosin [114], and troponin [104,115,116]. Table 9 summarizes the known autoantigens that are related to these cardiopathies in severe and hospitalized COVID-19 patients.…”

Section: Comparison With Previous Study Resultsmentioning

confidence: 99%

SARS-CoV-2 and Its Bacterial Co- or Super-Infections Synergize to Trigger COVID-19 Autoimmune Cardiopathies

Root‐Bernstein

Huber

Ziehl

et al. 2023

IJMS

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Autoimmune cardiopathies (AC) following COVID-19 and vaccination against SARS-CoV-2 occur at significant rates but are of unknown etiology. This study investigated the possible roles of viral and bacterial mimicry, as well as viral-bacterial co-infections, as possible inducers of COVID-19 AC using proteomic methods and enzyme-linked immunoadsorption assays. BLAST and LALIGN results of this study demonstrate that SARS-CoV-2 shares a significantly greater number of high quality similarities to some cardiac protein compared with other viruses; that bacteria such as Streptococci, Staphylococci and Enterococci also display very significant similarities to cardiac proteins but to a different set than SARS-CoV-2; that the importance of these similarities is largely validated by ELISA experiments demonstrating that polyclonal antibodies against SARS-CoV-2 and COVID-19-associated bacteria recognize cardiac proteins with high affinity; that to account for the range of cardiac proteins targeted by autoantibodies in COVID-19-associated autoimmune myocarditis, both viral and bacterial triggers are probably required; that the targets of the viral and bacterial antibodies are often molecularly complementary antigens such as actin and myosin, laminin and collagen, or creatine kinase and pyruvate kinase, that are known to bind to each other; and that the corresponding viral and bacterial antibodies recognizing these complementary antigens also bind to each other with high affinity as if they have an idiotype-anti-idiotype relationship. These results suggest that AC results from SARS-CoV-2 infections or vaccination complicated by bacterial infections. Vaccination against some of these bacterial infections, such as Streptococci and Haemophilus, may therefore decrease AC risk, as may the appropriate and timely use of antibiotics among COVID-19 patients and careful screening of vaccinees for signs of infection such as fever, diarrhea, infected wounds, gum disease, etc.

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

et al. 2023

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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.

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Compensatory Upregulation of Anti-Beta-Adrenergic Receptor Antibody Levels Might Prevent Heart Failure Presentation in Pediatric Myocarditis

Cited by 4 publications

References 26 publications

Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers

Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers

SARS-CoV-2 and Its Bacterial Co- or Super-Infections Synergize to Trigger COVID-19 Autoimmune Cardiopathies

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

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