Immunoadsorption in dilated cardiomyopathy: 6-month results from a randomized study

Staudt, Alexander; Hummel, Astrid; Ruppert, Jörg; Dörr, Marcus; Trimpert, Christiane; Birkenmeier, Katrin; Krieg, Thomas; Staudt, Yvonne; Felix, Stephan B.

doi:10.1016/j.ahj.2006.06.027

Cited by 99 publications

(89 citation statements)

References 26 publications

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“…These autoantibodies belong to IgG3 and are independent predictors of disease development within 5 years among healthy relatives of DCM patients [42]. Moreover, immunoadsorption to eliminate IgG or IgG3 with subsequent IgG substitution (IA/IgG) results in the improvement of LVEF and represents a novel, therapeutic approach in the treatment of DCM [11][12][13][14][15][16]. Consistent with previous studies [43][44][45] + LAP + T regs and B cells from controls (n = 4) were purified by FACS sorting and cocultured alone or at a 1:1 ratio for suppression and proliferation assay.…”

Section: Cd4mentioning

confidence: 99%

“…These autoantibodies belong to the IgG3 [9] and play an important role in the pathogenesis of DCM by initiating the disease process [10] or contributing to the progression of contractile dysfunction [6]. Several studies indicate that the use of immunoadsorption to eliminate IgG or IgG3 significantly improves cardiac performance and clinical status in heart-failure patients [11][12][13][14][15]. T regs are a subgroup of T cells that play a vital role in maintaining peripheral tolerance, preventing autoimmune diseases, and restraining chronic inflammatory diseases [16].…”

Section: Introductionmentioning

confidence: 99%

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Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy

Zhu

Tang

Dong

et al. 2015

Journal of Leukocyte Biology

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Section: Cd4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy

Zhu

Tang

Dong

et al. 2015

Journal of Leukocyte Biology

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“…In clinical site, Protein A and tryptophan conjugated columns are used in immunoadsorption therapy. 5,6) Even when these columns remove the IgG molecules in a nonselective manner, therapeutic effects are confirmed clinically. Therefore, therapeutic outcome for DCM can be expected by using ProA conjugated molecules as a navigator.…”

Section: Resultsmentioning

confidence: 98%

“…3,4) Recently, immunoadsorption therapy for DCM is evaluated in clinical trials, and improvement of the dilated cardiomyopathy was confirmed. 5,6) Protein A conjugated column is also used in the immunoadsorption therapy. 5) However, the patients are required to spend a significant amount of time weekly, the lifetime treatment costs are substantial, and there are associated QOL problems.…”

mentioning

confidence: 99%

A Novel Strategy for Etiologic Factor Removal: Drug-Navigated Clearance System (DNCS)

Mahara

Harada‐Shiba

Yamaoka

2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Here, we propose a novel therapeutic concept named drugnavigated clearance system (DNCS), in which a "navigator" decreases the concentration of a target etiologic factor in the blood by steering it to an unusual metabolic pathway. The navigator is composed of protein A (ProA) and dextran sulfate (DexS) and it successfully navigated antibodies (ABs), a model etiologic factor of dilated cardiomyopathy, to hepatocytes in vitro in the presence of low-density lipoprotein (LDL). ProA captured the Fc region of the target antibody while the DexS bound to LDL via the well-known electrostatic interaction. The hepatocytes simultaneously took up LDL via the LDL-receptor and internalized the AB/ProA-DexS complex that was bound to LDL. Therefore, this process demonstrates our attempt to navigate the etiologic factor to an alternate target pathway such as the LDL salvage.Key words metabolic abnormality; navigator; low-density lipoprotein; low-density lipoprotein receptor Increase in blood concentration of various etiologic factors has been known to cause different diseases. An effective and direct clinical strategy for reducing the blood concentration of these factors is apheresis. Furthermore, the removal of pathological autoantibodies in the blood has demonstrated therapeutic effects in diseases such as rheumatoid arthritis (RA) and dilated cardiomyopathy (DCM). Many groups reported that DCM is caused by accumulation of several autoantibodies including cardiac myosin and tropoin-I.1,2) The use of an absorption column in the extracorporeal circulation for the treatment of DCM is currently attracting considerable attention. 3,4) Recently, immunoadsorption therapy for DCM is evaluated in clinical trials, and improvement of the dilated cardiomyopathy was confirmed. 5,6) Protein A conjugated column is also used in the immunoadsorption therapy. 5) However, the patients are required to spend a significant amount of time weekly, the lifetime treatment costs are substantial, and there are associated QOL problems.Therefore, we attempted to develop a less invasive alternative strategy for apheresis and, here, are proposing a novel therapeutic concept called drug-navigated clearance system (DNCS). This strategy involves steering a target etiologic factor in the blood to an unusual metabolic path by the action of a "navigator," resulting in a reduction of the concentration of that factor in the blood. In the present study, we focused on an antibody as a model etiologic factor, while the low-density lipoprotein receptor (LDLR)-mediated LDL salvage pathway of the hepatocytes was selected as the eliminating route on account of its high capacity for LDL removal. 7,8) The LDLR binds not only LDL but also apolipoprotein E (apoE)-containing remnants of chylomicrons and very low-density lipoproteins (VLDLs).9) These receptors mediate cellular uptake and lysosomal hydrolysis.10-12) Therefore, LDLR-mediated uptake represented an attractive pathway for effective removal and hydrolysis of target molecules.The navigator, composed of protein A (ProA) ...

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“…Moreover, specific sub-groups responding to immunomodulating, immunosuppressive and antiviral therapy options have been identified based on the underlying pathomechanisms [13,14,15,16,17,18,19,20,21,22]. …”

Section: Introductionmentioning

confidence: 99%

The German Transregional Collaborative Research Centre ‘Inflammatory Cardiomyopathy – Molecular Pathogenesis and Therapy’

et al. 2009

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Objectives: This report focuses on the design and methods of the 3-centre clinical study of the Transregional Collaborative Research Centre ‘Inflammatory Cardiomyopathy – Molecular Pathogenesis and Therapy’, which aims to establish a comprehensive research registry on the diagnostics, therapy and disease outcomes of patients with inflammatory cardiomyopathy (CMi). The study goals are to investigate specific disease sub-entities and to develop standardised strategies for diagnostics and treatment. Methods: All consecutive patients with clinically suspected CMi, post-myocarditic cardiomyopathy and acute myocarditis are included in the research registry. Cardiopulmonary functional tests, clinical and patient data are obtained at baseline and subsequent readmission appointments and are linked to allow for prospective follow-up. Co-morbidities, quality of life, health- related behaviour and sociodemographic variables are ascertained using uniform self-administered questionnaires. Present Status: By May 2008, 2,061 cases had been included in the research registry (1,300 data-sets completed). At registration, 335 patients were diagnosed with CMi. The mean age was 50 ± 13 years and the mean ejection fraction was 39.9 ± 15.8%. Conclusions: The broad range of the acquired molecular-biological, histological, immunohistological, clinical and patient data makes this the most comprehensive research registry on patients with CMi to date.

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Immunoadsorption in dilated cardiomyopathy: 6-month results from a randomized study

Cited by 99 publications

References 26 publications

Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy

Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy

A Novel Strategy for Etiologic Factor Removal: Drug-Navigated Clearance System (DNCS)

The German Transregional Collaborative Research Centre ‘Inflammatory Cardiomyopathy – Molecular Pathogenesis and Therapy’

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