| 1. |
- Fu, Michael, 1963, et al.
(författare)
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Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension.
- 2000
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Ingår i: Journal of hypertension. - 0263-6352. ; 18:7, s. 945-53
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Tidskriftsartikel (refereegranskat)abstract
- Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.
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| 2. |
- Larsson, Lisa, 1976, et al.
(författare)
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Beneficial effect on cardiac function by intravenous immunoglobulin treatment in patients with dilated cardiomyopathy is not due to neutralization of anti-receptor autoantibody
- 2004
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Ingår i: Autoimmunity. - 0891-6934. ; 37:6-7, s. 489-493
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Tidskriftsartikel (refereegranskat)abstract
- Anti-beta1-adrenoceptor (beta1AR) autoantibodies have been shown to be pathophysiologically important in idiopathic dilated cardiomyopathy (DCM). Treatment with intravenous immunoglobulin (IVIG) has shown beneficial effects in both DCM and ischemic cardiomyopathy. However, the underlying mechanism has not been clarified. In the present study, we therefore examined whether the improvement of cardiac function was due to neutralization of functional beta1AR autoantibodies by anti-idiotypic antibodies. Autoantibodies against the beta1AR was analysed in sera from patients with DCM and coronary artery disease (CAD) treated with IVIG or placebo before, 6 and 12 months. Six month after treatment, DCM patients showed increase in beta1AR autoantibodies, mostly in IgG1 and IgG2, whereas in CAD patients mostly in IgG2. No changes in beta1AR autoantibodies after 12 months were detected. In summary, our results indicate that improvement of cardiac function by IVIG is not due to neutralization of beta1AR autoantibodies.
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| 3. |
- Mobini, Reza, 1965, et al.
(författare)
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A monoclonal antibody directed against an autoimmune epitope on the human beta1-adrenergic receptor recognized in idiopathic dilated cardiomyopathy.
- 2000
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Ingår i: Hybridoma. - : Mary Ann Liebert Inc. - 0272-457X. ; 19:2, s. 135-42
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Tidskriftsartikel (refereegranskat)abstract
- A monoclonal antibody (MAb M16) was obtained by immunizing Balb/C mice with free peptide H26R, corresponding to the second extracellular loop of the human beta1-adrenergic receptor (beta1AR), against which functional autoantibodies have been detected in patients with idiopathic dilated cardiomyopathy. The MAb was found to be of IgG2b type and directed against a conformational epitope, encompassing the sequence recognized by the human autoantibodies. BIAcore measurements yielded an equilibrium constant of 6.5 X 10(7) M1 with an association rate constant (kon) of 6.5 X 10(4) M(-1) sec(-1) and a dissociation rate constant (koff) of 1.0 X 10(-3) sec(-1). It immunoprecipitated only poorly the solubilized beta1AR of Sf9 cell membranes. Functionally, the MAb was capable of not only reducing the number of the maximal binding sites to the beta1-adrenergic receptor of transfected Sf9 cell membranes, but also of displaying a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These properties, which the MAb shares with the human autoantibodies, makes it an interesting tool for passive transfer studies in mice.
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