Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
Impact Factor (IF) – 1.227
Index Copernicus (ICV 2018) – 157.72
MNiSW – 40
Average rejection rate – 84.38%
ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download PDF

Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 9, September, p. 1257–1261

doi: 10.17219/acem/103668

Publication type: review article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Creative Commons BY-NC-ND 3.0 Open Access

Beyond the lungs: Alpha-1 antitrypsin’s potential role in human gestation

Aleksandra Jezela-Stanek1,A,B,D,F, Joanna Chorostowska-Wynimko1,C,E,F

1 Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warszawa, Poland

Abstract

Alpha-1 antitrypsin (AAT) is an acute-phase protein with strong inhibitory activity towards proteolytic enzymes, mainly elastase but also trypsin, chymotrypsin and thrombin. The biological role of the protein and the effects of its deficiency have been subjects of scientific research for years, yet in many areas our knowledge remains incomplete. Alpha-1 antitrypsin deficiency (AATD), a defect in AAT synthesis and functionality, is one of the most frequently inherited genetic disorders among Caucasian populations. Its severe form is characterized by very low serum levels of AAT, and it most often affects the lungs (causing early-onset emphysema or chronic obstructive lung disease (COPD)) and/or liver (leading to jaundice and liver cirrhosis in children and adults). However, little is known about other possible clinical consequences of AAT deficiency. We discuss AAT’s potential role in mechanisms regulating human fertility and gestation, with a particular emphasis on the clinical context and on indications for AATD diagnostic testing.

Key words

diagnosis, pregnancy, alpha-1 antitrypsin, oocyte maturation, alpha-1 antitrypsin deficiency

References (32)

  1. Chorostowska-Wynimko J, Popławska B, Janciauskiene S. Alfa-1 antytrypsyna: rola w fizjologii i patologii człowieka. International Review of Allergology and Clinical Immunology in Family Medicine. Family Med. 2012;18:22–28.
  2. De Serres F, Blanco I. Role of alpha-1 antitrypsin in human health and disease. J Intern Med. 2014;276(4):311–335.
  3. Chorostowska-Wynimko J, Bakuła A, Kulus M, et al. Standards for diagnosis and care of patients with inherited alpha-1 antitrypsin deficiency Recommendations of the Polish Respiratory Society, Polish Society of Pediatric Pulmonology and Polish Society of Pediatric Gastroenterology. Pneumonol Alergol Pol. 2016;84(3):193–202.
  4. Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: Diagnosis and treatment of pulmonary disease in alpha1-antitrypsin deficiency. Eur Respir J. 2017;50(5):1700610.
  5. Henao MP, Craig TJ. Understanding alpha-1 antitrypsin deficiency: A review with an allergist’s outlook. Allergy Asthma Proc. 2017;38(2):98–107.
  6. Stoller JK, Aboussouan LS. A review of α1-antitrypsin deficiency. Am J Respir Crit Care Med. 2012;185(3):246–259.)
  7. Janciauskiene S. Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles. Biochim Biophys Acta. 2001;1535(3):221–235.
  8. Faarvang HJ, Lauritsen OS. Increase of trypsin inhibitor in serum during pregnancy. Nature. 1963;199:290–291.
  9. Laurell CB, Rannevik G. A comparison of plasma protein changes induced by danazol, pregnancy, and estrogens. J Clin Endocrinol Metab. 1979;49(5):719–725.
  10. Laurell CB, Kullander S, Thorell J. Effect of administration of a combined estrogenprogestin contraceptive on the level of individual plasma proteins. Scand J Clin Lab Invest. 1968;21(4):337–343.
  11. Plaisier M, Dennert I, Rost E, Koolwijk P, van Hinsbergh VW, Helmerhorst FM. Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod. 2009;24(1):185–197.
  12. Pham CT. Neutrophil serine proteases fine-tune the inflammatory response. Int J Biochem Cell Biol. 2008;40(6–7):1317–1333.
  13. Quenby S, Bates M, Doig T, et al. Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod. 1999;14(9):2386–2391.
  14. Frochaux V, Hildebrand D, Talke A, Linscheid MW, Schlüter H. Alpha-1-antitrypsin: A novel human high temperature requirement protease A1 (HTRA1) substrate in human placental tissue. PLoS One. 2014;9(10):e109483.
  15. Wu YT, Wu Y, Zhang JY, et al. Preliminary proteomic analysis on the alterations in follicular fluid proteins from women undergoing natural cycles or controlled ovarian hyperstimulation. J Assist Reprod Genet. 2015;32(3):417–427.
  16. Madar T, Shahaf G, Sheiner E, et al. Low levels of circulating alpha-1 antitrypsin are associated with spontaneous abortions. J Matern Fetal Neonatal Med. 2013;26(18):1782–1787.
  17. Sobral M, Granja C, Sampaio M, Guerreiro F. Bleeding from oesophageal varices in pregnancy. BMJ Case Rep. 2013:26;2013.
  18. Twina G, Sheiner E, Shahaf G, et al. Lower circulation levels and activity of α-1 antitrypsin in pregnant women with severe preeclampsia. J Matern Fetal Neonatal Med. 2012;25(12):2667–2670.
  19. Feng YL, Zhou CJ, Li XM, Liang XQ. Alpha-1-antitrypsin acts as a preeclampsia-related protein: A proteomic study. Gynecol Obstet Invest. 2012;73(3):252–259.
  20. Greene DN, Procter M, Krautscheid P, Mao R, Lyon E, Grenache DG. α1-antitrypsin deficiency in fraternal twins born with familial spontaneous pneumothorax. Chest. 2012;141(1):239–241.
  21. Baron J, Sheiner E, Abecassis A, et al. α1-antitrypsin insufficiency is a possible contributor to preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2012;25(7):934–937.
  22. Kolialexi A, Tsangaris GT, Sifakis S, et al. Plasma biomarkers for the identification of women at risk for early onset preeclampsia. Expert Rev Proteomics. 2017;14(3):269–276.
  23. Narasimhan K, Lin SL, Tong T, et al. Maternal serum protein profile and immune response protein subunits as markers for non-invasive prenatal diagnosis of trisomy 21, 18, and 13. Prenat Diagn. 2013;33(3):223–231.
  24. Bianchi L, Gagliardi A, Campanella G, et al. A methodological and functional proteomic approach of human follicular fluid en route for oocyte quality evaluation. J Proteomics. 2013;90:61–76.
  25. Dai G, Lu G. Different protein expression patterns associated with polycystic ovary syndrome in human follicular fluid during controlled ovarian hyperstimulation. Reprod Fertil Dev. 2012;24(7):893–904.
  26. Anderson UD, Olsson MG, Kristensen KH, Åkerström B, Hansson SR. Review: Biochemical markers to predict preeclampsia. Placenta. 2012:Suppl33:S42–47.
  27. Feng Y, Wang N, Xu J, et al. Alpha-1-antitrypsin functions as a protective factor in preeclampsia through activating Smad2 and inhibitor of DNA binding 4. Oncotarget. 2017;8(68):113002–113012.
  28. Feng YL1, Yin YX2, Ding J1, Yang L, Xu J-J, Hu L-Q. Alpha-1-antitrypsin suppresses oxidative stress in preeclampsia by inhibiting the p38MAPK signaling pathway: An in vivo and in vitro study. PLoS One. 2017;12(3):e0173711.
  29. Hsu TY, Hsieh TT, Yang KD, et al. Proteomic profiling reveals alpha1-antitrypsin, alpha1microglobulin, and clusterin as preeclampsia-related serum proteins in pregnant women. Taiwan J Obstet Gynecol. 2015;54(5):499–504.
  30. Espana F, Gilabert J, Aznar J, Estelles A, Kobayashi T, Griffin JH. Complexes of activated protein C with alpha 1-antitrypsin in normal pregnancy and in severe preeclampsia. Am J Obstet Gynecol. 1991;164(5 Pt 1):1310–1316.
  31. Izumi-Yoneda N, Toda A, Okabe M, et al. Alpha 1 antitrypsin activity is decreased in human amnion in premature rupture of the fetal membranes. Mol Hum Reprod. 2009;15(1):49–57.
  32. Chorostowska-Wynimko J, Struniawski R, Sliwinski P, Wajda B, Czajkowska-Malinowska M. The National Alpha-1 Antitrypsin Deficiency Registry in Poland. COPD. 2015;12(S1):22–26.