Download PDF
CC BY-NC-ND 4.0 · Horm Metab Res 2020; 52(06): 379-385
DOI: 10.1055/a-1120-8647
Review

Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism

Lucie S. Meyer
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Germany
,
Siyuan Gong
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Germany
,
Martin Reincke
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Germany
,
Tracy Ann Williams
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Germany
2   Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy
› Author Affiliations Funding: M. Reincke is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 694913). T. A. Williams and M. Reincke are supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Projektnummer: 314061271-TRR 205.
› Further Information
Also available at
   Permissions and Reprints

Abstract

Primary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.

Key words

primary aldosteronism - angiotensin II receptor - autoantibodies - endocrine hypertension - adrenal cortex


Publication History

Received: 02 January 2020

Accepted: 12 February 2020

Article published online:
13 March 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Calhoun DA, Nishizaka MK, Zaman MA. et al. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40: 892-896
    Google Scholar
  • 2 Rossi GP, Bernini G, Caliumi C. et al. A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300
    Google Scholar
  • 3 Monticone S, Burrello J, Tizzani D. et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69: 1811-1820
    Google Scholar
  • 4 Mulatero P, Monticone S, Bertello C. et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab 2013; 98: 4826-4833
    Google Scholar
  • 5 Savard S, Amar L, Plouin PF. et al. Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension 2013; 62: 331-336
    Google Scholar
  • 6 Catena C, Colussi G, Lapenna R. et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007; 50: 911-918
    Google Scholar
  • 7 Zennaro MC, Boulkroun S, Fernandes-Rosa F. Genetic causes of functional adrenocortical adenomas. Endocr Rev 2017; 38: 516-537
    Google Scholar
  • 8 Prada ETA, Burrello J, Reincke M. et al. Old and new concepts in the molecular pathogenesis of primary aldosteronism. Hypertension 2017; 70: 875-881
    Google Scholar
  • 9 Wallukat G, Schimke I. Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases. Semin Immunopathol 2014; 36: 351-363
    Google Scholar
  • 10 Clark RB. Profile of Brian K. Kobilka and Robert J. Lefkowitz, 2012 Nobel laureates in chemistry. Proc Natl Acad Sci USA 2013; 110: 5274-5275
    Google Scholar
  • 11 Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature 2009; 459: 356-363
    Google Scholar
  • 12 Whalen EJ, Rajagopal S, Lefkowitz RJ. Therapeutic potential of beta-arrestin- and G protein-biased agonists. Trends Mol Med 2011; 17: 126-139
    Google Scholar
  • 13 Zhao P, Furness SGB. The nature of efficacy at G protein-coupled receptors. Biochem Pharmacol 2019; 170: 113647
    Google Scholar
  • 14 Turu G, Balla A, Hunyady L. The Role of beta-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor. Front Endocrinol (Lausanne) 2019; 10: 519
    Google Scholar
  • 15 Maning J, Negussie S, Clark MA. et al. Biased agonism/antagonism at the AngII-AT1 receptor: Implications for adrenal aldosterone production and cardiovascular therapy. Pharmacol Res 2017; 125: 14-20
    Google Scholar
  • 16 Lefkowitz RJ, Rajagopal K, Whalen EJ. New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors. Mol Cell 2006; 24: 643-652
    Google Scholar
  • 17 Li Y, Li XH, Yuan H. Angiotensin II type-2 receptor-specific effects on the cardiovascular system. Cardiovasc Diagn Ther 2012; 2: 56-62
    Google Scholar
  • 18 Patel S, Hussain T. Role of AT2R (Angiotensin Type 2 Receptor) in maintaining sodium-potassium balance. Hypertension 2018; 71: 563-565
    Google Scholar
  • 19 Liles C, Li H, Veitla V. et al. AT2R Autoantibodies Block Angiotensin II and AT1R Autoantibody-Induced Vasoconstriction. Hypertension 2015; 66: 830-835
    Google Scholar
  • 20 Terenzi R, Manetti M, Rosa I. et al. Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium. Sci Rep 2017; 7: 13293
    Google Scholar
  • 21 Levy BI. How to explain the differences between renin angiotensin system modulators. Am J Hypertens 2005; 18: 134s-141s
    Google Scholar
  • 22 Ludwig RJ, Vanhoorelbeke K, Leypoldt F. et al. Mechanisms of autoantibody-induced pathology. Front Immunol 2017; 8: 603
    Google Scholar
  • 23 Nagele EP, Han M, Acharya NK. et al. Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS One 2013; 8: e60726
    Google Scholar
  • 24 Wallukat G, Homuth V, Fischer T. et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999; 103: 945-952
    Google Scholar
  • 25 Fu ML, Herlitz H, Schulze W. et al. Autoantibodies against the Angiotensin Receptor (AT1) in patients with hypertension. J Hypertens 2000; 18: 945-953
    Google Scholar
  • 26 Taniguchi M, Rebellato LM, Cai J. et al. Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies. Am J Transplant 2013; 13: 2577-2589
    Google Scholar
  • 27 Reinsmoen NL, Lai CH, Heidecke H. et al. Anti-angiotensin type 1 receptor antibodies associated with antibody mediated rejection in donor HLA antibody negative patients. Transplantation 2010; 90: 1473-1477
    Google Scholar
  • 28 Banasik M, Boratynska M, Koscielska-Kasprzak K. et al. The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes. Transpl Int 2014; 27: 1029-1038
    Google Scholar
  • 29 Dragun D, Muller DN, Brasen JH. et al. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 2005; 352: 558-569
    Google Scholar
  • 30 Giral M, Foucher Y, Dufay A. et al. Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant 2013; 13: 2567-2576
    Google Scholar
  • 31 Jobert A, Rao N, Deayton S. et al. Angiotensin II type 1 receptor antibody precipitating acute vascular rejection in kidney transplantation. Nephrology (Carlton) 2015; 20 (Suppl. 01) 10-12
    Google Scholar
  • 32 Hesemann LE, Subramanian V, Mohanakumar T. et al. De novo development of antibodies to kidney-associated self-antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children. Pediatr Transplant 2015; 19: 499-503
    Google Scholar
  • 33 Lee DH, Heidecke H, Schroder A. et al. Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease. Mol Neurodegener 2014; 9: 49
    Google Scholar
  • 34 Riemekasten G, Philippe A, Nather M. et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis 2011; 70: 530-536
    Google Scholar
  • 35 Sabbadin C, Ceccato F, Ragazzi E. et al. Evaluation of angiotensin II type-1 receptor antibodies in primary aldosteronism and further considerations about their possible pathogenetic role. J Clin Hypertens (Greenwich) 2018; 20: 1313-1318
    Google Scholar
  • 36 Lefaucheur C, Viglietti D, Bouatou Y. et al. Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. Kidney Int 2019; 96: 189-201
    Google Scholar
  • 37 Piazza M, Seccia TM, Caroccia B. et al. AT1AA (Angiotensin II Type-1 Receptor Autoantibodies): Cause or Consequence of Human Primary Aldosteronism?. Hypertension 2019; 74: 793-799
    Google Scholar
  • 38 Williams TA, Jaquin D, Burrello J. et al. Diverse responses of autoantibodies to the Angiotensin II type 1 receptor in primary aldosteronism. Hypertension 2019; 74: 784-792
    Google Scholar
  • 39 Kem DC, Li H, Velarde-Miranda C, Liles C. et al. Autoimmune mechanisms activating the angiotensin AT1 receptor in 'primary' aldosteronism. J Clin Endocrinol Metab 2014; 99: 1790-1797
    Google Scholar
  • 40 Li H, Yu X, Cicala MV. et al. Prevalence of angiotensin II type 1 receptor (AT1R)-activating autoantibodies in primary aldosteronism. J Am Soc Hypertens 2015; 9: 15-20
    Google Scholar
  • 41 Fox R, Kitt J, Leeson P. et al. Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. J Clin Med 2019; 8 (PMID: 31590294)E1625 DOI: 10.3390/jcm8101625.
    Google Scholar
  • 42 Zhou CC, Zhang Y, Irani RA. et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 2008; 14: 855-862
    Google Scholar
  • 43 Thway TM, Shlykov SG, Day MC. et al. Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation. Circulation 2004; 110: 1612-1619
    Google Scholar
  • 44 Hubel CA, Wallukat G, Wolf M. et al. Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia. Hypertension 2007; 49: 612-617
    Google Scholar
  • 45 Siddiqui AH, Irani RA, Blackwell SC. et al. Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity. Hypertension 2010; 55: 386-393
    Google Scholar
  • 46 Dechend R, Viedt C, Muller DN. et al. AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Circulation 2003; 107: 1632-1639
    Google Scholar
  • 47 Yang X, Wang F, Chang H. et al. Autoantibody against AT1 receptor from preeclamptic patients induces vasoconstriction through angiotensin receptor activation. J Hypertens 2008; 26: 1629-1635
    Google Scholar
  • 48 Wenzel K, Rajakumar A, Haase H. et al. Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats. Hypertension 2011; 58: 77-84
    Google Scholar
  • 49 Leanos-Miranda A, Campos-Galicia I, Alvarez-Jimenez G. et al. Stimulating autoantibodies against the angiotensin II type 1 receptor are not associated with preeclampsia in Mexican-Mestizo women. J Hypertens 2010; 28: 834-841
    Google Scholar
  • 50 Birukov A, Muijsers HEC, Heidecke H. et al. Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia. Front Biosci (Landmark Ed) 2019; 24: 1462-1476
    Google Scholar
  • 51 Rossitto G, Regolisti G, Rossi E. et al. Elevation of angiotensin-II type-1-receptor autoantibodies titer in primary aldosteronism as a result of aldosterone-producing adenoma. Hypertension 2013; 61: 526-533
    Google Scholar
  • 52 Williams TA, Lenders JWM, Mulatero P. et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol 2017; 5: 689-699
    Google Scholar
  • 53 Dragun D, Catar R, Philippe A. Non-HLA antibodies against endothelial targets bridging allo- and autoimmunity. Kidney Int 2016; 90: 280-288
    Google Scholar
  • 54 Jahns R, Boege F. Questionable Validity of Peptide-Based ELISA Strategies in the Diagnostics of Cardiopathogenic Autoantibodies That Activate G-Protein-Coupled Receptors. Cardiology 2015; 131: 149-150
    Google Scholar
  • 55 Wisgerhof M, Carpenter PC, Brown RD. Increased adrenal sensitivity to angiotensin II in idiopathic hyperaldosteronism. J Clin Endocrinol Metab 1978; 47: 938-943
    Google Scholar
  • 56 Lymperopoulos A, Rengo G, Zincarelli C. et al. Adrenal beta-arrestin 1 inhibition in vivo attenuates post-myocardial infarction progression to heart failure and adverse remodeling via reduction of circulating aldosterone levels. J Am Coll Cardiol 2011; 57: 356-365
    Google Scholar
  • 57 Lymperopoulos A, Sturchler E, Bathgate-Siryk A. et al. Different potencies of angiotensin receptor blockers at suppressing adrenal beta-Arrestin1-dependent post-myocardial infarction hyperaldosteronism. J Am Coll Cardiol 2014; 64: 2805-2806
    Google Scholar