Immunoadsorption in dilated cardiomyopathy: long‐term reduction of cardiodepressant antibodies

Trimpert, Christiane; Herda, Lars R.; Eckerle, Lars; Pohle, Susanne; Müller, Carina; Landsberger, Martin; Felix, Stephan B.; Staudt, Alexander

doi:10.1111/j.1365-2362.2010.02314.x

Cited by 50 publications

(39 citation statements)

References 31 publications

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“…This could be an explanation for a prolonged beneficial effect of IA/IgG in DCM compared to IA without IgG substitution in IPAH, and might therefore also be considered for IPAH patients to prolong the beneficial effect of IA. In DCM, cardiotropic AAB are not detectable in all patients [25] . The same could apply to our IPAH patients and could be the reason for the nonresponse of those 3 of our patients that did not show any improvement in PVR.…”

Section: Hemodynamic Changes and Aab Levelsmentioning

confidence: 91%

“…Additionally, cardiac function improved after IA, marked by an increase in the CI by 13.1% after 3 months. Similarly, in patients suffering from DCM, Trimpert et al [25] detected a significant improvement in left ventricular function due to a reduction in cardiotropic AAB (AAB against sarcolemmal and mitochondrial proteins, surface receptors [β 1 -adrenoreceptor and M 1 muscarinic receptor], and heat shock proteins) and therefore an increase in contractility of the left ventricle. Several earlier studies have detected that IA combined with subsequent IgG substitution (IA/IgG) improves the left ventricular ejection fraction, enhances the CI and NYHA class [26][27][28] , reduces inflammation [29] , and decreases plasma levels of the prognostic heart failure markers nt-BNP and 270 nt-ANP [30] in patients suffering from DCM.…”

Section: Hemodynamic Changes and Aab Levelsmentioning

confidence: 95%

“…In the present study, a more significant effect of IA was not seen 3 months after IA, when the AAB concentrations had returned to, or even surpassed, the levels measured at baseline. Trimpert et al [25] observed a longer-lasting beneficial effect on cardiac function in DCM patients up to 6-12 months after IA in combination with subsequent IgG substitution. IgG substitution was primarily carried out for safety reasons to avoid acute infections, but it influences the immune system through various mechanisms at the same time.…”

Section: Hemodynamic Changes and Aab Levelsmentioning

confidence: 98%

“…Trimpert et al [25] demonstrated in patients suffering from DCM that 4 monthly repeated courses of IA/IgG therapy were not superior to a single course of 5 consecutive IA sessions and IgG substitution. The reason for that was the nearly complete removal of cardiotropic AAB until 6 months after the initial IA/IgG course, so that additional IA courses would have no additional effect.…”

Section: Frequency Of Ia Coursesmentioning

confidence: 99%

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Safety and Efficacy of Immunoadsorption as an Add-On to Medical Treatment in Patients with Severe Idiopathic Pulmonary Arterial Hypertension

Nagel¹,

Ewert²,

Egenlauf³

et al. 2017

Respiration

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Background: Despite optimized medical therapy, severe idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease with a poor outcome. Autoantibodies have been detected in IPAH that can contribute to worsening of the disease. Objectives: The objective of this prospective, open-label, single-arm, multicenter trial was to evaluate the safety and efficacy of immunoadsorption (IA) as an add-on to optimized medical treatment for patients with IPAH. Methods: A total of 10 IPAH patients received IA over 5 days. Their clinical parameters, including hemodynamics measured by right heart catheter, were assessed at baseline and after 3 and 6 months. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included the change in 6-min walking distance, quality of life, safety, and plasma levels of IgG and autoantibodies. Results: The evaluation of the 10 IPAH patients (75% female; 51 ± 12 years; 166 ± 10 cm; WHO functional class III; 53% on combination therapy) revealed that IA was a safe procedure that efficiently removed IgG and autoantibodies from the circulation. After 3 months, the mean PVR improved significantly by 13.2% (p = 0.03) and the cardiac index improved by 13.1%, but no significant changes were found in 6-min walking distance. The quality of life physical functioning subscale score significantly improved after 6 months. The serious adverse events in 3 patients were possibly related to IA and included pneumonia, temporary disturbance in attention, and thrombocytopenia. Conclusions: IA as an add-on to targeted medical treatment for IPAH is a safe procedure with beneficial effects on hemodynamics, especially in patients with high levels of autoantibodies. Larger-scale controlled studies are needed to assess its efficacy in IPAH and to identify responders.

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Section: Hemodynamic Changes and Aab Levelsmentioning

confidence: 91%

Section: Hemodynamic Changes and Aab Levelsmentioning

confidence: 95%

Section: Hemodynamic Changes and Aab Levelsmentioning

confidence: 98%

Section: Frequency Of Ia Coursesmentioning

confidence: 99%

See 2 more Smart Citations

Safety and Efficacy of Immunoadsorption as an Add-On to Medical Treatment in Patients with Severe Idiopathic Pulmonary Arterial Hypertension

Nagel¹,

Ewert²,

Egenlauf³

et al. 2017

Respiration

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show abstract

“…Thus, patients with shorter disease duration and a more impaired left ventricular function at baseline have been shown to respond with a greater increase in cardiac function as measured by LVEF (Staudt et al 2010). Moreover, detection of NIA in the plasma of DCM patients, before IA, may predict acute and prolonged hemodynamic improvement during IA/IgG (Staudt et al 2004;Trimpert et al 2010). However, these variables did not allow sufficient prediction of the responder state to IA/IgG and thus did not permit the discrimination between responders and non-responders.…”

Section: Prediction Of Response To Ia In Dcm By Biomarkers-an Approacmentioning

confidence: 99%

Use of Biomarkers for the Prediction of Treatment Response: Immunoadsorption in Dilated Cardiomyopathy as a Clinical Example

Dörr

Völker

Felix

2015

Individualized Medicine

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In this article, we outline a clinical example illustrating how integrated analyses of biomarkers might be used for the prediction of treatment response. We report findings from a pilot study that investigated the hemodynamic effects of a novel treatment option, immunoadsorption with subsequent IgG substitution (IA/IgG), in patients with dilated cardiomyopathy. Several previous studies have shown that this treatment leads to a significant improvement of cardiac function and relief of symptoms. Response to this therapy is, however, characterized by a wide inter-individual variability. In a pilot study, we tested the value of clinical, biochemical and molecular parameters for prediction of the response to IA/IgG. This study demonstrated that combined assessment of two markers (negative inotropic activity of antibodies in the blood and gene expression patterns derived from myocardial biopsies) predicts response to this therapy with an extremely high sensitivity and specificity, thereby enabling appropriate selection of patients who most likely benefit from this therapeutic intervention. Further studies will screen for biomarker signatures in blood, which do not depend on endomyocardial biopsies, and will compare responders and non-responders with respect to other molecular markers (e.g. plasma proteome, metabolome and microRNA profiles as well as whole blood transcriptome signatures). In the future, such strategies might facilitate selection of patients with dilated cardiomyopathy who are responders not only to immunoadsorption therapy but also to other heart failure treatments for which a heterogeneous response is observed and thus will help to offer more effective treatments to affected patients.

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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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Immunoadsorption in dilated cardiomyopathy: long‐term reduction of cardiodepressant antibodies

Abstract: IA/IgG therapy induces long-term reduction of negative inotropic antibodies. After 12 months, however, re-increase of negative inotropic antibodies cannot be excluded.

Cited by 50 publications

References 31 publications

Safety and Efficacy of Immunoadsorption as an Add-On to Medical Treatment in Patients with Severe Idiopathic Pulmonary Arterial Hypertension

Safety and Efficacy of Immunoadsorption as an Add-On to Medical Treatment in Patients with Severe Idiopathic Pulmonary Arterial Hypertension

Use of Biomarkers for the Prediction of Treatment Response: Immunoadsorption in Dilated Cardiomyopathy as a Clinical Example

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

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