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Immune Modulation in Heart Failure: the Promise of Novel Biologics

  • Heart Failure (W Tang, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

Immune system activation plays a central role in heart failure progression. Large-scale immune modulatory clinical trials targeting tumor necrosis factor-α and broad spectrum immune modulation have been negative. The objective of this review is to highlight past, present, and what is in the horizon for the immunomodulation in heart failure with a focus of biologics.

Recent findings

Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising. The potential of cell therapy for immune modulation is increasingly recognized in clinical trials. Strategies targeting anti-cardiac antibodies such as immunoadsorption and intravenous immunoglobulin have been used in clinical practice with positive outcomes but large pragmatic clinical trials are lacking. The use of an aptamer to block anti-cardiac antibodies is undergoing phase 1 clinical evaluation. Promising targets include inflammasomes, toll-like receptors, chemokines, natural killer cells, and macrophages.

Summary

Large-scale immune modulatory clinical trials have been negative. Nevertheless, the experience gained from them along with increasing understanding of molecular mechanisms of immune pathophysiology in heart failure is leading to rapid recognition of new therapeutic targets and approaches.

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References and Recommended Reading

  1. Arutyunov GP, Kostyukevich OI, Serov RA, Rylova NV, Bylova NA. Collagen accumulation and dysfunctional mucosal barrier of the small intestine in patients with chronic heart failure. Int J Cardiol. 2008;125(2):240–5. https://doi.org/10.1016/j.ijcard.2007.11.103.

    Article  PubMed  Google Scholar 

  2. Kitai T, Kirsop J, Tang WH. Exploring the microbiome in heart failure. Curr Heart Fail Rep. 2016;13(2):103–9. https://doi.org/10.1007/s11897-016-0285-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sager HB, Kessler T, Schunkert H. Monocytes and macrophages in cardiac injury and repair. J Thorac Dis. 2017;9(Suppl 1):S30–5. https://doi.org/10.21037/jtd.2016.11.17.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tracchi I, Ghigliotti G, Mura M, Garibaldi S, Spallarossa P, Barisione C, et al. Increased neutrophil lifespan in patients with congestive heart failure. Eur J Heart Fail. 2009;11(4):378–85. https://doi.org/10.1093/eurjhf/hfp031.

    Article  CAS  PubMed  Google Scholar 

  5. Levick SP, Melendez GC, Plante E, McLarty JL, Brower GL, Janicki JS. Cardiac mast cells: the centrepiece in adverse myocardial remodelling. Cardiovasc Res. 2011;89(1):12–9. https://doi.org/10.1093/cvr/cvq272.

    Article  CAS  PubMed  Google Scholar 

  6. Sugi Y, Yasukawa H, Kai H, Fukui D, Futamata N, Mawatari K, et al. Reduction and activation of circulating dendritic cells in patients with decompensated heart failure. Int J Cardiol. 2011;147(2):258–64. https://doi.org/10.1016/j.ijcard.2009.09.524.

    Article  PubMed  Google Scholar 

  7. Vredevoe DL, Widawski M, Fonarow GC, Hamilton M, Martínez-Maza O, Gage JR. Interleukin-6 (IL-6) expression and natural killer (NK) cell dysfunction and anergy in heart failure. Am J Cardiol. 2004;93(8):1007–11. https://doi.org/10.1016/j.amjcard.2003.12.054.

    Article  CAS  PubMed  Google Scholar 

  8. Clark DJ, Cleman MW, Pfau SE, Rollins SA, Ramahi TM, Mayer C, et al. Serum complement activation in congestive heart failure. Am Heart J. 2001;141(4):684–90. https://doi.org/10.1067/mhj.2001.113758.

    Article  CAS  PubMed  Google Scholar 

  9. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323(4):236–41. https://doi.org/10.1056/NEJM199007263230405.

    Article  CAS  PubMed  Google Scholar 

  10. Naftali-Shani, N., Levin-Kotler L.P., Palevski D., Amit U., Kain D., Landa N., Hochhauser E., Leor J., <span hwp:id="article-title-1" class="article-title">Left ventricular dysfunction switches mesenchymal stromal cells toward an inflammatory phenotype and impairs their reparative properties via toll-like receptor-4</span><span hwp:id="article-title-48" class="sub-article-title">clinical perspective</span>. Circulation, 2017. 135(23): p. 2271–2287, https://doi.org/10.1161/CIRCULATIONAHA.116.023527.

  11. Timmers L, Sluijter JPG, van Keulen JK, Hoefer IE, Nederhoff MGJ, Goumans MJ, et al. Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ Res. 2008;102(2):257–64. https://doi.org/10.1161/CIRCRESAHA.107.158220.

    Article  CAS  PubMed  Google Scholar 

  12. Knuefermann P, Schwederski M, Velten M, Krings P, Ehrentraut H, Rudiger M, et al. Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9. Cardiovasc Res. 2008;78(1):26–35. https://doi.org/10.1093/cvr/cvn011.

    Article  CAS  PubMed  Google Scholar 

  13. Dhondup Y, Sjaastad I, Scott H, Sandanger Ø, Zhang L, Haugstad SB, et al. Sustained toll-like receptor 9 activation promotes systemic and cardiac inflammation, and aggravates diastolic heart failure in SERCA2a KO mice. PLoS One. 2015;10(10):e0139715. https://doi.org/10.1371/journal.pone.0139715.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Van Tassell BW, Raleigh JM, Abbate A. Targeting interleukin-1 in heart failure and inflammatory heart disease. Curr Heart Fail Rep. 2015;12(1):33–41. https://doi.org/10.1007/s11897-014-0231-7.

    Article  PubMed  Google Scholar 

  15. deFilippi CR, Christenson RH. Evolving role of galectin-3 as a cardiac biomarker: heart failure with preserved ejection fraction and renal function, important pieces of the puzzle. JACC Heart Fail. 2015;3(3):253–6. https://doi.org/10.1016/j.jchf.2014.12.009.

    Article  PubMed  Google Scholar 

  16. Dieplinger B, Mueller T. Soluble ST2 in heart failure. Clin Chim Acta. 2015;443:57–70. https://doi.org/10.1016/j.cca.2014.09.021.

    Article  CAS  PubMed  Google Scholar 

  17. Damas JK, et al. CXC-chemokines, a new group of cytokines in congestive heart failure—possible role of platelets and monocytes. Cardiovasc Res. 2000;45(2):428–36. https://doi.org/10.1016/S0008-6363(99)00262-X.

    Article  CAS  PubMed  Google Scholar 

  18. Waehre A, Vistnes M, Sjaastad I, Nygård S, Husberg C, Lunde IG, et al. Chemokines regulate small leucine-rich proteoglycans in the extracellular matrix of the pressure-overloaded right ventricle. J Appl Physiol (1985). 2012;112(8):1372–82. https://doi.org/10.1152/japplphysiol.01350.2011.

    Article  CAS  Google Scholar 

  19. Matsubara J et al.. Incremental prognostic significance of the elevated levels of pentraxin 3 in patients with heart failure with normal left ventricular ejection fraction. J Am Heart Assoc, 2014. 3(4).

  20. Cordero-Reyes AM, Youker KA, Torre-Amione G. The role of B-cells in heart failure. Methodist Debakey Cardiovasc J. 2013;9(1):15–9. https://doi.org/10.14797/mdcj-9-1-15.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kaya Z, Leib C, Katus HA. Autoantibodies in heart failure and cardiac dysfunction. Circ Res. 2012;110(1):145–58. https://doi.org/10.1161/CIRCRESAHA.111.243360.

    Article  CAS  PubMed  Google Scholar 

  22. Laroumanie F, Douin-Echinard V, Pozzo J, Lairez O, Tortosa F, Vinel C, et al. CD4+ T cells promote the transition from hypertrophy to heart failure during chronic pressure overload. Circulation. 2014;129(21):2111–24. https://doi.org/10.1161/CIRCULATIONAHA.113.007101.

    Article  CAS  PubMed  Google Scholar 

  23. Tang H, Zhong Y, Zhu Y, Zhao F, Cui X, Wang Z. Low responder T cell susceptibility to the suppressive function of regulatory T cells in patients with dilated cardiomyopathy. Heart. 2010;96(10):765–71. https://doi.org/10.1136/hrt.2009.184945.

    Article  CAS  PubMed  Google Scholar 

  24. Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ Res. 2015;116(7):1254–68. https://doi.org/10.1161/CIRCRESAHA.116.302317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhu ZF, Tang TT, Dong WY, Li YY, Xia N, Zhang WC, et al. Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy. J Leukoc Biol. 2015;97(4):797–805. https://doi.org/10.1189/jlb.5A1014-469RR.

    Article  CAS  PubMed  Google Scholar 

  26. Altara R, et al. The CXCL10/CXCR3 Axis and cardiac inflammation: implications for immunotherapy to treat infectious and noninfectious diseases of the heart. J Immunol Res. 2016;2016:4396368.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Janicki JS, Brower GL, Levick SP. The emerging prominence of the cardiac mast cell as a potent mediator of adverse myocardial remodeling. Methods in molecular biology (Clifton, NJ). 2015;1220:121–39. https://doi.org/10.1007/978-1-4939-1568-2_8.

    Article  CAS  Google Scholar 

  28. Kubota T, Bounoutas GS, Miyagishima M, Kadokami T, Sanders VJ, Bruton C, et al. Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy. Circulation. 2000;101(21):2518–25. https://doi.org/10.1161/01.CIR.101.21.2518.

    Article  CAS  PubMed  Google Scholar 

  29. Bozkurt B, Torre-Amione G, Warren MS, Whitmore J, Soran OZ, Feldman AM, et al. Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation. 2001;103(8):1044–7. https://doi.org/10.1161/01.CIR.103.8.1044.

    Article  CAS  PubMed  Google Scholar 

  30. Birks EJ. Molecular changes after left ventricular assist device support for heart failure. Circ Res. 2013;113(6):777–91. https://doi.org/10.1161/CIRCRESAHA.113.301413.

    Article  CAS  PubMed  Google Scholar 

  31. Nagarajan V, Hernandez AV, Cauthen CA, Starling RC, Tang WHW. Usefulness of cell-mediated immune function in risk stratification for patients with advanced heart failure. Am Heart J. 2017;183:35–9. https://doi.org/10.1016/j.ahj.2016.09.008.

    Article  PubMed  Google Scholar 

  32. Murphy KM, Rosenthal JL. Progress in the presence of failure: updates in chronic systolic heart failure management. Curr Treat Options Cardiovasc Med. 2017;19(7):50. https://doi.org/10.1007/s11936-017-0552-4.

    Article  PubMed  Google Scholar 

  33. Iborra-Egea O, Gálvez-Montón C, Roura S, Perea-Gil I, Prat-Vidal C, Soler-Botija C, et al. Mechanisms of action of sacubitril/valsartan on cardiac remodeling: a systems biology approach. NPJ Systems Biology and Applications. 2017;3(1):12. https://doi.org/10.1038/s41540-017-0013-4.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ma Y, Chilton RJ, Lindsey ML. Heart rate reduction: an old and novel candidate heart failure therapy. Hypertension. 2012;59(5):908–10. https://doi.org/10.1161/HYPERTENSIONAHA.111.186494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Medicine., U.S.N.L.o. ClinicalTrials.gov 2017 [cited 2017 11/22/2017]; Available from: https://clinicaltrials.gov/ct2/results?cond=Heart+Failure&term=immune&cntry1=&state1=&Search=Search&recrs=a&recrs=b.

  36. Torre-Amione G, Kapadia S, Lee J, Durand JB, Bies RD, Young JB, et al. Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation. 1996;93(4):704–11. https://doi.org/10.1161/01.CIR.93.4.704.

    Article  CAS  PubMed  Google Scholar 

  37. Gullestad L, Ueland T, Fjeld JG, Holt E, Gundersen T, Breivik K, et al. Effect of thalidomide on cardiac remodeling in chronic heart failure: results of a double-blind, placebo-controlled study. Circulation. 2005;112(22):3408–14. https://doi.org/10.1161/CIRCULATIONAHA.105.564971.

    Article  CAS  PubMed  Google Scholar 

  38. Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the randomized Etanercept worldwide evaluation (RENEWAL). Circulation. 2004;109(13):1594–602. https://doi.org/10.1161/01.CIR.0000124490.27666.B2.

    Article  CAS  PubMed  Google Scholar 

  39. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT, Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation. 2003;107(25):3133–40. https://doi.org/10.1161/01.CIR.0000077913.60364.D2.

    Article  CAS  PubMed  Google Scholar 

  40. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101(4):890–8. https://doi.org/10.1172/JCI1112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature. 1997;390(6658):350–1. https://doi.org/10.1038/37022.

    Article  CAS  PubMed  Google Scholar 

  42. Torre-Amione G, Sestier F, Radovancevic B, Young J. Effects of a novel immunemodulation therapy in patients with advanced chronic heart failure: results of a randomized, controlled, phase II trial. J Am Coll Cardiol. 2004;44(6):1181–6. https://doi.org/10.1016/j.jacc.2004.06.047.

    Article  PubMed  Google Scholar 

  43. Torre-Amione G, Anker SD, Bourge RC, Colucci WS, Greenberg BH, Hildebrandt P, et al. Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial. Lancet. 2008;371(9608):228–36. https://doi.org/10.1016/S0140-6736(08)60134-8.

    Article  CAS  PubMed  Google Scholar 

  44. Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT, et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest. 1999;104(3):271–80. https://doi.org/10.1172/JCI6709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Birks EJ, Felkin LE, Banner NR, Khaghani A, Barton PJR, Yacoub MH. Increased toll-like receptor 4 in the myocardium of patients requiring left ventricular assist devices. J Heart Lung Transplant. 2004;23(2):228–35. https://doi.org/10.1016/S1053-2498(03)00106-2.

    Article  PubMed  Google Scholar 

  46. Gao W, et al. Inhibition of toll-like receptor signaling as a promising therapy for inflammatory diseases: a journey from molecular to nano therapeutics. Front Physiol. 2017;8:508.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wang L, Li YL, Zhang CC, Cui W, Wang X, Xia Y, et al. Inhibition of toll-like receptor 2 reduces cardiac fibrosis by attenuating macrophage-mediated inflammation. Cardiovasc Res. 2014;101(3):383–92. https://doi.org/10.1093/cvr/cvt258.

    Article  CAS  PubMed  Google Scholar 

  48. Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni ML, Debuque R, et al. Revisiting cardiac cellular composition. Circ Res. 2016;118(3):400–9. https://doi.org/10.1161/CIRCRESAHA.115.307778.

    Article  CAS  PubMed  Google Scholar 

  49. Frantz S, Nahrendorf M. Cardiac macrophages and their role in ischaemic heart disease. Cardiovasc Res. 2014;102(2):240–8. https://doi.org/10.1093/cvr/cvu025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Nahrendorf M, Swirski FK. Monocyte and macrophage heterogeneity in the heart. Circ Res. 2013;112(12):1624–33. https://doi.org/10.1161/CIRCRESAHA.113.300890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21(7):677–87. https://doi.org/10.1038/nm.3893.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Val-Blasco A, Piedras MJGM, Ruiz-Hurtado G, Suarez N, Prieto P, Gonzalez-Ramos S, et al. Role of NOD1 in heart failure progression via regulation of Ca(2+) handling. J Am Coll Cardiol. 2017;69(4):423–33. https://doi.org/10.1016/j.jacc.2016.10.073.

    Article  CAS  PubMed  Google Scholar 

  53. Damas JK, et al. Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure—modulatory effect of intravenous immunoglobulin. J Am Coll Cardiol. 2001;38(1):187–93. https://doi.org/10.1016/S0735-1097(01)01335-3.

    Article  CAS  PubMed  Google Scholar 

  54. Jiang Y, Bai J, Tang L, Zhang P, Pu J. Anti-CCL21 antibody attenuates infarct size and improves cardiac remodeling after myocardial infarction. Cell Physiol Biochem. 2015;37(3):979–90. https://doi.org/10.1159/000430224.

    Article  CAS  PubMed  Google Scholar 

  55. Takahashi T. Toll-like receptors and myocardial contractile dysfunction. Cardiovasc Res. 2008;78(1):3–4. https://doi.org/10.1093/cvr/cvn044.

    Article  CAS  PubMed  Google Scholar 

  56. Knowlton AA. Paying for the tolls: the high cost of the innate immune system for the cardiac myocyte. In: Sattler S, Kennedy-Lydon T, editors. The immunology of cardiovascular homeostasis and pathology. Cham: Springer International Publishing; 2017. p. 17–34. https://doi.org/10.1007/978-3-319-57613-8_2.

    Chapter  Google Scholar 

  57. Sakata Y, Dong JW, Vallejo JG, Huang CH, Baker JS, Tracey KJ, et al. Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2007;292(1):H503–9. https://doi.org/10.1152/ajpheart.00642.2006.

    Article  CAS  PubMed  Google Scholar 

  58. Topkara VK, Chambers KT, Yang KC, Tzeng HP, Evans S, Weinheimer C, et al. Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling. JCI Insight. 2016;1(4):e86038. https://doi.org/10.1172/jci.insight.86038.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wang J-W, Fontes MSC, Wang X, Chong SY, Kessler EL, Zhang YN, et al. Leukocytic toll-like receptor 2 deficiency preserves cardiac function and reduces fibrosis in sustained pressure overload. Sci Rep. 2017;7(1):9193. https://doi.org/10.1038/s41598-017-09451-3.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Shishido T, Nozaki N, Yamaguchi S, Shibata Y, Nitobe J, Miyamoto T, et al. Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction. Circulation. 2003;108(23):2905–10. https://doi.org/10.1161/01.CIR.0000101921.93016.1C.

    Article  CAS  PubMed  Google Scholar 

  61. Sager HB, Dutta P, Dahlman JE, Hulsmans M, Courties G, Sun Y, et al. RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Sci Transl Med. 2016;8(342):342ra80. https://doi.org/10.1126/scitranslmed.aaf1435.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Sager HB, Hulsmans M, Lavine KJ, Moreira MB, Heidt T, Courties G, et al. Proliferation and recruitment contribute to myocardial macrophage expansion in chronic heart failure. Circ Res. 2016;119(7):853–64. https://doi.org/10.1161/CIRCRESAHA.116.309001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Jung M, Ma Y, Iyer RP, DeLeon-Pennell KY, Yabluchanskiy A, Garrett MR, et al. IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. Basic Res Cardiol. 2017;112(3):33. https://doi.org/10.1007/s00395-017-0622-5.

    Article  PubMed  Google Scholar 

  64. Hasan AS, Luo L, Yan C, Zhang TX, Urata Y, Goto S, et al. Cardiosphere-derived cells facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment. PLoS One. 2016;11(10):e0165255. https://doi.org/10.1371/journal.pone.0165255.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Palaniyandi SS, Sun L, Ferreira JC, Mochly-Rosen D. Protein kinase C in heart failure: a therapeutic target? Cardiovasc Res. 2009;82(2):229–39. https://doi.org/10.1093/cvr/cvp001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Li J, Jubair S, Levick SP, Janicki JS. The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis. IJC Metabolic & Endocrine. 2016;10(Supplement C):16–23. https://doi.org/10.1016/j.ijcme.2015.11.003.

    Article  Google Scholar 

  67. Yoshikawa T, Baba A, Akaishi M, Wakabayashi Y, Monkawa T, Kitakaze M, et al. Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column—a prospective, multicenter, randomized, within-patient and parallel-group comparative study to evaluate efficacy and safety. J Clin Apher. 2016;31(6):535–44. https://doi.org/10.1002/jca.21446.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Haberland A, Holtzhauer M, Schlichtiger A, Bartel S, Schimke I, Müller J, et al. Aptamer BC 007—a broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors. Eur J Pharmacol. 2016;789:37–45. https://doi.org/10.1016/j.ejphar.2016.06.061.

    Article  CAS  PubMed  Google Scholar 

  69. Stephenson E, Savvatis K, Mohiddin SA, Marelli-Berg FM. T-cell immunity in myocardial inflammation: pathogenic role and therapeutic manipulation. Br J Pharmacol. 2017;174(22):3914–25. https://doi.org/10.1111/bph.13613.

    Article  CAS  PubMed  Google Scholar 

  70. Youker KA, Assad-Kottner C, Cordero-Reyes AM, Trevino AR, Flores-Arredondo JH, Barrios R, et al. High proportion of patients with end-stage heart failure regardless of aetiology demonstrates anti-cardiac antibody deposition in failing myocardium: humoral activation, a potential contributor of disease progression. Eur Heart J. 2014;35(16):1061–8. https://doi.org/10.1093/eurheartj/eht506.

    Article  CAS  PubMed  Google Scholar 

  71. Nagatomo Y, McNamara DM, Alexis JD, Cooper LT, Dec GW, Pauly DF, et al. Myocardial recovery in patients with systolic heart failure and autoantibodies against beta1-adrenergic receptors. J Am Coll Cardiol. 2017;69(8):968–77. https://doi.org/10.1016/j.jacc.2016.11.067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Muller J, Wallukat G, Dandel M, Bieda H, Brandes K, Spiegelsberger S, et al. Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy. Circulation. 2000;101(4):385–91. https://doi.org/10.1161/01.CIR.101.4.385.

    Article  CAS  PubMed  Google Scholar 

  73. Dandel M, Wallukat G, Englert A, Lehmkuhl HB, Knosalla C, Hetzer R. Long-term benefits of immunoadsorption in beta(1)-adrenoceptor autoantibody-positive transplant candidates with dilated cardiomyopathy. Eur J Heart Fail. 2012;14(12):1374–88. https://doi.org/10.1093/eurjhf/hfs123.

    Article  CAS  PubMed  Google Scholar 

  74. Ohlow MA, Brunelli M, Schreiber M, Lauer B. Therapeutic effect of immunoadsorption and subsequent immunoglobulin substitution in patients with dilated cardiomyopathy: results from the observational prospective Bad Berka Registry. J Cardiol. 2017;69(2):409–16. https://doi.org/10.1016/j.jjcc.2016.07.014.

    Article  PubMed  Google Scholar 

  75. Nevers T, Salvador AM, Grodecki-Pena A, Knapp A, Velázquez F, Aronovitz M, et al. Left ventricular T-cell recruitment contributes to the pathogenesis of heart failure. Circ Heart Fail. 2015;8(4):776–87. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bansal SS, Ismahil MA, Goel M, Patel B, Hamid T, Rokosh G, et al. Activated T lymphocytes are essential drivers of pathological remodeling in ischemic heart failure. Circ Heart Fail. 2017;10(3):e003688. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Okamoto N, Noma T, Ishihara Y, Miyauchi Y, Takabatake W, Oomizu S, et al. Prognostic value of circulating regulatory T cells for worsening heart failure in heart failure patients with reduced ejection fraction. Int Heart J. 2014;55(3):271–7. https://doi.org/10.1536/ihj.13-343.

    Article  CAS  PubMed  Google Scholar 

  78. Wang H, Hou L, Kwak D, Fassett J, Xu X, Chen A, et al. Increasing regulatory T cells with Interleukin-2 and Interleukin-2 antibody complexes attenuates lung inflammation and heart failure progression. Hypertension. 2016;68(1):114–22. https://doi.org/10.1161/HYPERTENSIONAHA.116.07084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kallikourdis M, Martini E, Carullo P, Sardi C, Roselli G, Greco CM, et al. T cell costimulation blockade blunts pressure overload-induced heart failure. Nat Commun. 2017;8:14680. https://doi.org/10.1038/ncomms14680.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015;116(8):1413–30. https://doi.org/10.1161/CIRCRESAHA.116.303614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Cardiovascular Diseases, Section of Heart Failure and Transplant, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA

    Paulino Alvarez MD & Alexandros Briasoulis MD PhD

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  2. Alexandros Briasoulis MD PhD
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Correspondence to Paulino Alvarez MD.

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This article is part of the Topical Collection on Heart Failure

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Alvarez, P., Briasoulis, A. Immune Modulation in Heart Failure: the Promise of Novel Biologics. Curr Treat Options Cardio Med 20, 26 (2018). https://doi.org/10.1007/s11936-018-0617-z

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  • DOI: https://doi.org/10.1007/s11936-018-0617-z

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