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Elevated M2-muscarinic and β1-adrenergic receptor autoantibody levels are associated with paroxysmal atrial fibrillation

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Abstract

Background

Pathophysiologic mechanisms underlying lone atrial fibrillation (AF) have not been clearly demonstrated yet. Emerging evidence has indicated that autoimmunity may play a role in the development of AF. Relationship between serum anti-M2-muscarinic receptor autoantibody (anti-M2-R) and anti-β1-adrenergic receptor autoantibody (anti-β1-R) levels and lone paroxysmal atrial fibrillation (PAF) has not been investigated. We aimed to compare anti-M2-R and anti-β1-R levels between lone PAF patients and healthy control subjects.

Methods and results

75 patients with lone PAF (age: 52.80 ± 6.80 years, 53 % male) and 75 healthy control subjects (age: 53.30 ± 6.80 years, 54 % male) were enrolled in the study. Serum anti-M2-R and anti-β1-R levels were measured by ELISA and compared between two groups. Anti-M2-R [142.30 (77.65–400.00) vs. 69.00 (39.48–299.04) ng/mL; p < 0.001) and anti-β1-R [102.56 (65.18–348.41) vs. 44.17 (30.89–158.54) ng/mL; p < 0.001] levels were significantly higher in patients with lone PAF compared to healthy controls. Multivariate regression analysis showed that left atrial diameter (OR: 1.471, p < 0.001), hs-CRP(OR: 1.940, p < 0.001), anti-M2-R (OR: 1.158, p < 0.001) and anti-β1-R (OR: 1.296, p < 0.001) levels were independent predictors for the presence of lone PAF. Using a cut-off level of 101.83 ng/mL, anti-M2-R levels predicted presence of lone PAF with a sensitivity of 94.68 % and specificity of 81.33 %. Anti-β1-R levels predicted presence of lone PAF with a sensitivity of 92.00 % and specificity of 73.30 %, using a cut-off level of 72.16 ng/mL.

Conclusion

Our results demonstrated that higher serum anti-M2-R and anti-β1-R levels are associated with lone PAF. Autoantibodies related to autonomic system may play an important role in the development of lone AF.

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References

  1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P, Guidelines-CPG ESCCfP, Document R (2012) 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation—developed with the special contribution of the European Heart Rhythm Association. Europace 14(10):1385–1413. doi:10.1093/europace/eus305

    Article  PubMed  Google Scholar 

  2. Linz D, van Hunnik A, Ukena C, Ewen S, Mahfoud F, Schirmer SH, Lenski M, Neuberger HR, Schotten U, Bohm M (2014) Renal denervation: effects on atrial electrophysiology and arrhythmias. Clin Res Cardiol: Off J Ger Card Soc. doi:10.1007/s00392-014-0695-1

    Google Scholar 

  3. Zhang M, Tao H, Shi KH (2014) Renal denervation as a friend of catheter ablation in patients with atrial fibrillation and hypertension. Clin Res Cardiol: Off J Ger Card Soc. doi:10.1007/s00392-014-0752-9

    Google Scholar 

  4. Greif M, von Ziegler F, Wakili R, Tittus J, Becker C, Helbig S, Laubender RP, Schwarz W, D’Anastasi M, Schenzle J, Leber AW, Becker A (2013) Increased pericardial adipose tissue is correlated with atrial fibrillation and left atrial dilatation. Clin Res Cardiol: Off J Ger Card Soc 102(8):555–562. doi:10.1007/s00392-013-0566-1

    Article  CAS  Google Scholar 

  5. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Huezey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Smith SC Jr, Priori SG, Estes NA 3rd, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Tarkington LG, Yancy CW, American College of Cardiology Foundation, American Heart Association Task F (2011) 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 123(10):e269–e367. doi:10.1161/CIR.0b013e318214876d

    Article  PubMed  Google Scholar 

  6. Wyse DG, Van Gelder IC, Ellinor PT, Go AS, Kalman JM, Narayan SM, Nattel S, Schotten U, Rienstra M (2014) Lone atrial fibrillation: does it exist? J Am Coll Cardiol 63(17):1715–1723. doi:10.1016/j.jacc.2014.01.023

    Article  PubMed  Google Scholar 

  7. Kallwellis-Opara A, Dorner A, Poller WC, Noutsias M, Kuhl U, Schultheiss HP, Pauschinger M (2007) Autoimmunological features in inflammatory cardiomyopathy. Clin Res Cardiol: Off J Ger Card Soc 96(7):469–480. doi:10.1007/s00392-007-0524-x

    Article  CAS  Google Scholar 

  8. Baba A, Fu M (2008) Autoantibodies in atrial fibrillation: actor, biomaker or bystander? Autoimmunity 41(6):470–472. doi:10.1080/08916930802031504

    Article  CAS  PubMed  Google Scholar 

  9. Maixent JM, Paganelli F, Scaglione J, Levy S (1998) Antibodies against myosin in sera of patients with idiopathic paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 9(6):612–617

    Article  CAS  PubMed  Google Scholar 

  10. Zou C, Zhang Z, Zhao W, Li G, Ma G, Yang X, Zhang J, Zhang L (2013) Predictive value of pre-procedural autoantibodies against M2-muscarinic acetylcholine receptor for recurrence of atrial fibrillation one year after radiofrequency catheter ablation. J Transl Med 11:7. doi:10.1186/1479-5876-11-7

    Article  CAS  PubMed  Google Scholar 

  11. Novikova DS, Bekbosynova MS, Antidze T, Loladze NV, Domogatskii SP, Golitsyn SP, Nasonov EL, Denisova IA, Tonevitskii SP (2004) Autoantibodies against beta(1)-adrenoreceptors in patients with cardiac rhythm disorders. prevalence and possible role in development of arrhythmia. Kardiologiia 44(7):17–22

    CAS  PubMed  Google Scholar 

  12. Mandal K, Jahangiri M, Mukhin M, Poloniecki J, Camm AJ, Xu Q (2004) Association of anti-heat shock protein 65 antibodies with development of postoperative atrial fibrillation. Circulation 110(17):2588–2590. doi:10.1161/01.CIR.0000136825.96029.A5

    Article  CAS  PubMed  Google Scholar 

  13. Baba A, Yoshikawa T, Fukuda Y, Sugiyama T, Shimada M, Akaishi M, Tsuchimoto K, Ogawa S, Fu M (2004) Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy. Eur Heart J 25(13):1108–1115. doi:10.1016/j.ehj.2004.05.012

    Article  CAS  PubMed  Google Scholar 

  14. Stavrakis S, Yu X, Patterson E, Huang S, Hamlett SR, Chalmers L, Pappy R, Cunningham MW, Morshed SA, Davies TF, Lazzara R, Kem DC (2009) Activating autoantibodies to the beta-1 adrenergic and m2 muscarinic receptors facilitate atrial fibrillation in patients with Graves’ hyperthyroidism. J Am Coll Cardiol 54(14):1309–1316. doi:10.1016/j.jacc.2009.07.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Chiale PA, Ferrari I, Mahler E, Vallazza MA, Elizari MV, Rosenbaum MB, Levin MJ (2001) Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction. Circulation 103(13):1765–1771

    Article  CAS  PubMed  Google Scholar 

  16. Brisinda D, Sorbo AR, Venuti A, Ruggieri MP, Manna R, Fenici P, Wallukat G, Hoebeke J, Frustaci A, Fenici R (2012) Anti-beta-adrenoceptors autoimmunity causing ‘idiopathic’ arrhythmias and cardiomyopathy. Circ J: Off J Jpn Circ Soc 76(6):1345–1353

    Article  CAS  Google Scholar 

  17. Kurt M, Tanboga IH, Karakas MF, Buyukkaya E, Akcay AB, Sen N, Bilen E (2012) The relationship between atrial electromechanical delay and P-wave dispersion with the presence and severity of metabolic syndrome. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 40(8):663–670. doi:10.5543/tkda.2012.97404

    Article  Google Scholar 

  18. Hong CM, Zheng QS, Liu XT, Shang FJ, Wang HT, Jiang WR (2009) Effects of autoantibodies against M2 muscarinic acetylcholine receptors on rabbit atria in vivo. Cardiology 112(3):180–187. doi:10.1159/000149152

    Article  CAS  PubMed  Google Scholar 

  19. Chiale PA, Garro HA, Schmidberg J, Sanchez RA, Acunzo RS, Lago M, Levy G, Levin M (2006) Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac beta andrenergic receptors. Heart rhythm: Off J Heart Rhythm Soc 3(10):1182–1186. doi:10.1016/j.hrthm.2006.06.011

    Article  Google Scholar 

  20. Chiale PA, Rosenbaum MB, Elizari MV, Hjalmarson A, Magnusson Y, Wallukat G, Hoebeke J (1995) High prevalence of antibodies against beta 1- and beta 2-adrenoceptors in patients with primary electrical cardiac abnormalities. J Am Coll Cardiol 26(4):864–869. doi:10.1016/0735-1097(95)00262-2

    Article  CAS  PubMed  Google Scholar 

  21. Christ T, Wettwer E, Dobrev D, Adolph E, Knaut M, Wallukat G, Ravens U (2001) Autoantibodies against the beta 1 adrenoceptor from patients with dilated cardiomyopathy prolong action potential duration and enhance contractility in isolated cardiomyocytes. J Mol Cell Cardiol 33(8):1515–1525. doi:10.1006/jmcc.2001.1414

    Article  CAS  PubMed  Google Scholar 

  22. Molina CE, Leroy J, Richter W, Xie M, Scheitrum C, Lee IO, Maack C, Rucker-Martin C, Donzeau-Gouge P, Verde I, Llach A, Hove-Madsen L, Conti M, Vandecasteele G, Fischmeister R (2012) Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. J Am Coll Cardiol 59(24):2182–2190. doi:10.1016/j.jacc.2012.01.060

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Hacettepe University Scientific Research Projects Coordination Unit (845).

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Correspondence to Kadri M. Gurses.

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Yalcin, M.U., Gurses, K.M., Kocyigit, D. et al. Elevated M2-muscarinic and β1-adrenergic receptor autoantibody levels are associated with paroxysmal atrial fibrillation. Clin Res Cardiol 104, 226–233 (2015). https://doi.org/10.1007/s00392-014-0776-1

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