P1888Autoantiboides to Muscarinic M2 cholinoceptors in patients with paroxysmal atrial fibrillation

Abstract Introduction Atrial fibrillation (AFib) is the most frequenly encountered arrhythmia. In the majority of cases AFib occurs in patients with cardiovascular diseases such as arterial hypertension (AH). In 10–15% of cases AFib occurs in the absense of comorbidities in structurally normal heart. It is reffered to as “lone AFib” and the cause of this arrhythmia remains unknown. Activation of cardiac M2-actylcholinoreceptors (M2-CR) leads to decrease in duration of atrial refractory periods that may contribute to development of AFib. Autoantibodies against M2-CR has cholinomimetic properties, but role of these autoantibodies in development and maintenance of AFib has not been studied. Purpose To assess autoantibodies against M2-CR in patients with paroxysmal lone AFib, in patients with AFib and AH and healthy people. Methods 100 patints with lone Afib, 100 patients with Afib and AH and 25 healthy people were included. Patients underwent clinical blood and urinlysis, assessment of biochemistry blood panel, 12-lead ECG, 24-hour Holter monitoring, echocardiography and stress-testing (treadmill or stress-echocardiography). Assesment of IgM and IgG autoantibodies to M2-CR was performed by indirect immunoenzyme assay. The following peptide molecules were used as epitopes for detection of autoantibodies: M1-amino acid sequence YTVIGYWPLGVVCDL (83–98) of the first extracellular loop of M2-CR; M2-sequence VRTVEDGECYIQFFSNAAVTFGTAI (168–192) of the second extracellular loop of M2-CR; M3-sequence NTFCAPCIPNTV (410–421) of the third extracellular loop of M2-CR, M4-short sequence VEDGECYIQFFS (171–182) of the second extracellular loop of M2-CR; M1+M4-chimeric molecule formed by sequences of the first and the second extacellular loops of M2-CR connected by disulfide bound YTVIGYWPLGVVCDL+VEDGECTIQFFS (83–98+171–182). Results IgG to M2-CR were found in 32% of patients with AFib and in 12% of healthy subjects (p