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Autoimmune basis for postural tachycardia syndrome Li H; Yu X; Liles C; Khan M; Vanderlinde-Wood M; Galloway A; Zillner C; Benbrook A; Reim S; Collier D; Hill MA; Raj SR; Okamoto LE; Cunningham MW; Aston CE; Kem DCJ Am Heart Assoc 2014[Feb]; 3 (1): e000755BACKGROUND: Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR). METHODS AND RESULTS: Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for alpha1AR autoantibody-mediated contractility using a perfused rat cremaster arteriole assay. A receptor-transfected cell-based assay was used to detect the presence of beta1AR and beta2AR autoantibodies. Data were normalized and expressed as a percentage of baseline. The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69+/-3% compared to 91+/-1% of baseline for healthy controls, P<0.001) when coexisting beta2AR dilative activity was blocked; and this was suppressed by alpha1AR blockade with prazosin. POTS sera acted as a partial alpha1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased beta1AR activation (130+/-3% of baseline, P<0.01) and a subset had increased beta2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced beta1AR and beta2AR agonist activity. Autoantibody-positive POTS sera demonstrated specific binding to beta1AR, beta2AR, and alpha1AR in transfected cells. CONCLUSIONS: POTS patients have elevated alpha1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of alpha1AR for vasoconstriction and concurrent betaAR-mediated tachycardia. Coexisting beta1AR and beta2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.|*Autoimmunity[MESH]|*Hemodynamics/drug effects[MESH]|Adrenergic Agonists/pharmacology[MESH]|Adult[MESH]|Animals[MESH]|Autoantibodies/*blood[MESH]|Autoimmune Diseases/blood/diagnosis/*immunology/physiopathology[MESH]|Biological Assay[MESH]|Biomarkers/blood[MESH]|CHO Cells[MESH]|Case-Control Studies[MESH]|Cricetinae[MESH]|Cricetulus[MESH]|Dose-Response Relationship, Drug[MESH]|Female[MESH]|Heart Rate[MESH]|Humans[MESH]|Male[MESH]|Middle Aged[MESH]|Oklahoma[MESH]|Postural Orthostatic Tachycardia Syndrome/blood/diagnosis/*immunology/physiopathology[MESH]|Rats[MESH]|Receptors, Adrenergic, alpha-1/immunology[MESH]|Receptors, Adrenergic, beta-1/immunology[MESH]|Receptors, Adrenergic, beta-2/immunology[MESH]|Receptors, Adrenergic/drug effects/genetics/*immunology[MESH]|Tennessee[MESH]|Transfection[MESH]|Vasoconstriction[MESH]|Vasodilation[MESH]|Young Adult[MESH] |
