Antibodies to angiotensin-converting enzyme 2 in infertile patients with a history of COVID-19 and in fertile women

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Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS) that affects fertility in women. Antibodies against ACE2 have predictive value for COVID-19 and may contribute to RAS dysregulation and reproductive failure.

Objective: To investigate the prevalence and levels of anti-ACE2 autoantibodies in infertile patients with a history of COVID-19 and in fertile women.

Materials and methods: Serum anti-ACE2 autoantibodies (M, G) were determined by ELISA in infertile patients with a history of COVID-19 (group 1, n=121), without a history of COVID-19 (group 2, n=79), and in fertile women (group 3, n=80). The association between antibodies against ACE2, SARS-CoV-2, thyroid antigens, and hormones was investigated.

Results: Patients in groups 1 and 2 had higher rates of inflammatory gynecologic diseases, pelvic surgery, spontaneous miscarriages, and thyroid pathology than those in group 3. Anti-ACE2 antibodies were detected more frequently (40.5% and 38.8 %) and had higher levels in infertile patients than in fertile women (20%). Women with a history of COVID-19 were more likely to have anti-ACE2 IgG. Antibodies against ACE2 were significantly correlated with those against FSH.

Conclusion: Patients with infertility, irrespective of a history of COVID-19, have a higher prevalence and higher anti-ACE2 antibody levels than fertile women. Anti-ACE2 antibodies are associated with primary and secondary infertility, and may be involved in the pathophysiology of infertility.

作者简介

Irina Menzhinskaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

编辑信件的主要联系方式.
Email: i_menzinskaya@oparina4.ru

Dr. Med. Sci., Leading Researcher, Laboratory of Clinical Immunology

俄罗斯联邦, Moscow

Darya Ermakova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: daria.ermakova.97@bk.ru

Postgraduate Student

俄罗斯联邦, Moscow

Anastasia Syrkasheva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_syrkasheva@oparina4.ru

PhD, Senior Researcher

俄罗斯联邦, Moscow

Yulia Drapkina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: yu_drapkina@oparina4.ru

PhD, Researcher

俄罗斯联邦, Moscow

Natalia Dolgushina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_dolgushina@oparina4.ru

Dr. Med. Sci., Deputy Director for Science

俄罗斯联邦, Moscow

参考

  1. Gheblawi M., Wang K., Viveiros A., Nguyen Q., Zhong J.C., Turner A.J. et al. Angiotensin-сonverting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ. Res. 2020; 126(10): 1456-74. https://dx.doi.org/10.1161/CIRCRESAHA.120.317015.
  2. Valenzuela R., Pedrosa M.A., Garrido-Gil P., Labandeira C.M., Navarro G., Franco R. et al. Interactions between ibuprofen, ACE2, renin-angiotensin system, and spike protein in the lung. Implications for COVID-19. Clin. Transl. Med. 2021; 11: e371. https://dx.doi.org/10.1002/ctm2.371.
  3. Pedrosa M.A., Valenzuela R., Garrido-Gil P., Labandeira C.M., Navarro G., Franco R. et al. Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19. Clin. Sci. 2021; 135(3): 465-81. https://dx.doi.org/10.1042/CS20201511.
  4. Beyerstedt S., Casaro E.B., Rangel É.B. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur. J. Clin. Microbiol. Infect. Dis. 2021; 40(5): 905-19. https://dx.doi.org/10.1007/s10096-020-04138-6.
  5. Lanza K., Perez L.G., Costa L.B., Cordeiro T.M., Palmeira V.A., Ribeiro V.T. et al. COVID-19: the renin-angiotensin system imbalance hypothesis. Clin Sci. 2020; 134(11): 1259-64. https://dx.doi.org/10.1042/CS20200492.
  6. Verdecchia P., Cavallini C., Spanevello A., Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection, Eur. J. Intern. Med. 2020; 76: 14-20. https://dx.doi.org/10.1016/j.ejim.2020.04.037.
  7. Arthur J.M., Forrest J.C., Boehme K.W., Kennedy J.L., Owens S., Herzog C., Harville T.O. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS One. 2021; 16(9): e0257016. https://dx.doi.org/10.1371/journal.pone.0257016.
  8. Rodriguez-Perez A.I., Labandeira C.M., Pedrosa M.A., Valenzuela R., Suarez-Quintanilla J.A., Cortes-Ayaso M. et al. Autoantibodies against ACE2 and angiotensin type-1 receptors increase severity of COVID-19. J. Autoimmun. 2021; 122: 102683. https://dx.doi.org/10.1016/j.jaut.2021.102683.
  9. Labandeira C.M., Pedrosa M.A., Suarez-Quintanilla J.A., Cortes-Ayaso M., Labandeira-García J.L., Rodríguez-Pérez A.I. Angiotensin system autoantibodies correlate with routine prognostic indicators for COVID-19 severity. Front. Med. 2022; 9: 840662. https://dx.doi.org/10.3389/fmed.2022.840662.
  10. Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46(4): 586-90. https://dx.doi.org/10.1007/s00134-020-05985-9.
  11. Li M.-Y., Li L., Zhang Y., Wang X.-S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis. Poverty. 2020; 9(1): 45. https://dx.doi.org/10.1186/s40249-020-00662-x.
  12. Jing Y., Run-Qian L., Hao-Ran W., Hao-Ran C., Ya-Bin L., Yang G., Fei C. Potential influence of COVID-19/ACE2 on the female reproductive system. Mol. Hum. Reprod. 2020; 26(6): 367-73. https://dx.doi.org/10.1093/molehr/gaaa030.
  13. Zeng L., Xia S., Yuan W., Yan K., Xiao F., Shao J., Zhou W. Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr. 2020; 174(7): 722-5. https://dx.doi.org/10.1001/jamapediatrics.2020.0878.
  14. Cavallo I.K., Dela Cruz C., Oliveira M.L., Del Puerto H.L., Dias J.A., Lobach V.N. et al. Angiotensin-(1-7) in human follicular fluid correlates with oocyte maturation. Hum. Reprod. 2017; 32(6): 1318-24. https://dx.doi.org/10.1093/humrep/dex072.
  15. Reis F.M., Bouissou D.R., Pereira V.M., Camargos A.F., dos Reis A.M., Santos R.A. Angiotensin-(1-7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertil. Steril. 2011; 95(1): 176-81. https://dx.doi.org/10.1016/j.fertnstert.2010.06.060.
  16. Menzhinskaya I.V., Gladkova K.A., Sidelnikova V.M., Sukhikh G.T. Antiprogesterone antibodies in clinic of habitualloss pregnancy. Immunology. 2008; 29(1): 34-7 (in Russian).
  17. Menzhinskaya I.V., Kashentseva M.M., Vanko L.V., Sukhikh G.T. Immunochemical properties of autoantibodies aganst chorionic gonadotropin in women with pregnancy loss. Immunology. 2015; 36(1): 30-5. (in Russian).
  18. Soro-Paavonen A., Gordin D., Forsblom C., Rosengard-Barlund M., Waden J., Thorn L. et al. Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications. J. Hypertens. 2012; 30(2): 375-83. https://dx.doi.org/10.1097/HJH.0b013e32834f04b6.
  19. Varagic J., Ahmad S., Nagata S., Ferrario C.M. ACE2: angiotensin II/angiotensin-(1–7) balance in cardiac and renal injury. Curr. Hypertens. Rep. 2014; 16(3): 420. https://dx.doi.org/10.1007/s11906-014-0420-5.
  20. Park S.E., Kim W.J., Park S.W., Park J.W., Lee N., Park C.Y., Youn B.S. High urinary ACE2 concentrations are associated with severity of glucose intolerance and microalbuminuria. Eur. J. Endocrinol. 2013; 168(2): 203-10. https://dx.doi.org/10.1530/EJE-12-0782.
  21. Takahashi Y., Haga S., Ishizaka Y., Mimori A. Autoantibodies to angiotensin-converting enzyme 2 in patients with connective tissue diseases. Arthritis Res. Ther. 2010; 12(3): R85. https://dx.doi.org/10.1186/ ar3012.
  22. Pour S.K., Scoville C., Susan S. Tavernier S.S., Aghazadeh-Habashi A. Plasma angiotensin peptides as biomarkers of rheumatoid arthritis are correlated with anti-ACE2 auto-an https://dx.doi.org/tibodies level and disease intensity. Inflammopharmacology. 2022; 30(4): 1295-302. https://dx.doi.org/10.1007/s10787-022-01008-9.
  23. Pereira V.M., Reis F.M., Santos R.A.S., Cassali G.D., Santos S.H.S., Honorato-Sampaio K., dos Reis A.M. Gonadotropin Stimulation Increases the Expression of Angiotensin-(1–7) and Mas Receptor in the Rat Ovary. Reprod. Sci. 2009; 16(12): 1165-74. https://dx.doi.org/10.1177/1933719109343309.
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