Background —Idiopathic dilated cardiomyopathy (IDC) frequently is a progressive disease without causative therapy options. Following the hypothesis that in certain patients autoantibodies against cardiac structures may induce, maintain, or promote the progression of the disease, we investigated whether the elimination of these autoantibodies through immunoadsorption would improve cardiac function. Methods and Results —This prospective case-control study included 34 patients with IDC. Each patient presented with moderate to severe heart failure and evidence of autoantibodies directed against β 1 -adrenoceptors (β 1 -AABs). Seventeen patients received standard medical therapy (control group), whereas 17 were also treated with immunoadsorption (treatment group) to eliminate β 1 -AABs. A 1-year follow-up included echocardiographic assessment of left ventricular ejection fraction and internal diameters, β 1 -AAB levels, and clinical status every 3 months. Within 1 year, the mean±SD left ventricular ejection fraction rose from 22.3±3.3% to 37.9±7.9% ( P =0.0001) in the treatment group, with a relative increase of 69.9%. However, in the control group, no overall increase was seen (from 23.8±3.0% to 25.2±5.9%, P =0.3154). Left ventricular diameter in diastole decreased by 14.5% from 74.5±7.1 to 63.7±6.0 mm in the treatment group ( P =0.0001) and by 3.8% ( P =0.2342) in the control group. In the treatment group, the NYHA functional rating improved after immunoadsorption ( P =0.0001). β 1 -AABs did not increase anew. Conclusions —In IDC, the use of immunoadsorption is superior to the use of standard medical therapy. It significantly improves cardiac performance and clinical status.
In a pig model for AMI, we observed that selective CRP-apheresis significantly reduces CRP levels and the volume of the infarction zone after AMI. Additionally, it changes the morphology of the scars and preserves cardiac output (LVEF).
Glaucoma is a frequent ocular disease that may lead to blindness. Primary open-angle glaucoma (POAG) and ocular hypertension (OHT) are common diseases with increased intraocular pressure (IOP), which are mainly responsible for these disorders. Their pathogenesis is widely unknown. We screened the sera of patients with POAG and OHT for the prevalence of autoantibodies (AAb) against G protein-coupled receptors (GPCRs) in comparison to controls. Employing frequency modulation of spontaneously contracting neonatal rat cardiomyocytes in vitro, agonistic GPCR AAb were to be detected in roughly 75% of the patients with POAG and OHT, however, not in controls. Using inhibitory peptides the AAb’ target was identified as β2 adrenergic receptor (β2AR). The AAb interact with the second extracellular loop of β2AR. The peptides 181–187 and 186–192 were identified as binding sites of the AAb within the extracellular loop II. The binding of the AAb to β2ARs was verified by surface-plasmon-resonance analysis. The isotype of the AAb was (immunoglobulin) IgG3. In an additional pilot principal-of-proof study, including four patients with POAG, the removal of the AAb against the β2AR and other immunoglobulins G by immunoadsorption resulted in a transient reduction of IOP. These findings might indicate a possible role of agonistic AAb directed against β2ARs in the dynamics of aqueous humor and might support a contribution of adaptive autoimmunity in the etiopathogenesis of POAG and OHT.
Peptides as ligands for immunoadsorption exhibit several potential advantages over native proteins. Two newly developed adsorbers are based on peptides covalently coupled to sepharose CL-4B. Globaffin is capable of binding immunoglobulins independent from their antigen specificity and thus, applicable in transplant recipients and several antibody mediated autoimmune diseases. Among others, the most important disorders suitable for the treatment with Globaffin are rheumatoid arthritis, systemic lupus erythematosus, and acute renal transplant rejection. Coraffin is a specific adsorber using two linear peptide ligands mimicking epitopes of the beta1-adrenergic receptor, that bind corresponding autoantibodies from patients suffering from idiopathic dilated cardiomyopathy. Specific immunoadsorption has been shown to be beneficial for patients with dilated cardiomyopathy. Coraffin can be used as a new therapeutic option for these patients, who get only limited benefit from medical therapy. Both adsorbers may be combined with all approved apheresis control devices available.
Although primary causes of Alzheimer’s and vascular dementia are unknown, the importance of preceding vascular lesions is widely accepted. Furthermore, there is strong evidence for the involvement of autoimmune mechanisms. Here, we report the presence of agonistic autoantibodies directed at adrenergic receptors in the circulation of patients with mild to moderate Alzheimer’s and vascular dementia. In 59% of these patients, agonistic autoantibodies against the α1‐adrenergic receptor and the β2‐adrenergic receptor were identified. The majority of positive patients (66%) contained both types of autoantibodies in combination. In a control group of patients with neurological impairments others than Alzheimer’s and vascular dementia, only 17% were found to harbour these autoantibodies. The autoantibodies to the α1‐adrenergic receptor interacted preferably with the extracellular loop1 of the receptor. They were further studied in IgG preparations from the column regenerate of a patient who underwent immunoadsorption. The α1‐adrenergic receptor autoantibodies specifically bound to the extracellular loop1 peptide of the receptor with an apparent EC50 value of 30 nm. They mobilized intracellular calcium in a clonal cell line expressing the human form of the α1‐adrenergic receptor. Our data support the notion that autoimmune mechanisms play a significant role in the pathogenesis of Alzheimer’s and vascular dementia. We suggest that agonistic autoantibodies to the α1‐adrenergic and the β2‐adrenergic receptor may contribute to vascular lesions and increased plaque formation.
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