The Utilization of Alpha-1 Anti-trypsin (A1AT) in Infectious Disease Monitoring and Treatment

Year 2019, Volume: 09 Issue: 01, 51 - 58, 15.03.2019

İrene L. Indalao Agustiningsih Agustiningsih Eka Pratiwi Kartika Dewi Puspa Hartanti Dian Ikawati Ririn Ramadhany

https://doi.org/10.5799/jmid.537178

Abstract

Alpha
one anti-trypsin (A1AT) is a major serine protease inhibitor found circulating
in human blood. A1AT related studies mainly focus on A1AT potential biomarker
as well as therapeutic target in non-infectious diseases. Their findings
indicate A1AT beneficial features may also be applied for monitoring and
treating infectious disease. However, only a few studies have reviewed A1AT’s
useful properties as a biomarker and therapeutic agent for infectious diseases.
This narrative review aims to summarize growing evidences that support the idea
of utilizing A1AT as a tool for monitoring and therapy for infectious diseases.

A1AT
showed potential as a biomarker for a wide spectrum of infectious disease, from
virus, bacteria, to parasite. Its level and functionality were proposed to
predict risk for disease susceptibility or progression and to indicate response
therapy. As promising therapeutic agent in various infectious diseases, the
administration of A1AT has shown antimicrobial activity, immunomodulatory and
anti-apoptotic effect, in addition to more familiar function, suppressing
excessive proteolysis.

The
broad utilization of A1AT, both as biomarker and therapeutic agent, in studies
on infectious diseases seems promising. However, there are issues need to be
investigated further before establishing its feasibility as a monitoring and
therapy tool against infection diseases.  J
Microbiol Infect Dis 2019; 9(1): 51-58.

Keywords

Alpha-1 anti-trypsin, virus, bacteria, biomarker, drug, infection, parasite, protozoa, review

References

• 1. Gooptu B, Ekeowa UI, Lomas DA. Mechanisms of emphysema in alpha1-antitrypsin deficiency: molecular and cellular insights. Eur Respir J 2009; 34(2):475-88. 2. Lussier B, Wilson AA. Alpha-1 Antitrypsin. In: Wanner A, Sandhaus RS, editors. Alpha-1 Antitrypsin, Switzerland: Springer International Publishing; 2016, p. 17-30. 3. McElvaney NG. Alpha-1 antitrypsin therapy in cystic fibrosis and the lung disease associated with alpha-1 antitrypsin deficiency. Ann Am Thorac Soc 2016; 13(6):S191-S196. 4. Korkmaz B, Poutrain P, Hazouard E, De Monte M, Attucci S, Gauthier FL. Competition between elastase and related proteases from human neutrophil for binding to α1-protease inhibitor. Am J Respir Cell Mol Biol 2005; 32(6):553-559. 5. Serban KA, Petrache I. Alpha-1 antitrypsin and lung cell apoptosis. Ann Am Thorac Soc 2016;13 (Supplement 2):S146-149. 6. Hurley K, Reeves EP, Carroll TP, McElvaney NG. Tumor necrosis factor-α driven inflammation in alpha-1 antitrypsin deficiency: a new model of pathogenesis and treatment. Expert Rev Respir Med 2015; 6348:1-16. 7. Janciauskiene S, Welte T. Well-known and less well-known functions of Alpha-1 antitrypsin: Its role in chronic obstructive pulmonary disease and other disease developments. Ann Am Thorac Soc 2016; 13:S280-S288. 8. Chiuchiolo MJ, Crystal RG. Gene therapy for alpha-1 antitrypsin deficiency lung disease. Ann Am Thorac Soc 2016; 13:S352-S369. 9. McElvaney NG. Diagnosing α1-antitrypsin deficiency: How to improve the current algorithm. Eur Respir Rev 2015; 24(135):52-57. 10. Lewis EC. Expanding the Clinical Indications for α1-Antitrypsin Therapy. Mol Med 2012; 18(6):957-970. 11. Brebner JA, Stockley RA. Recent advances in α-1-antitrypsin deficiency-related lung disease. Expert Rev Respir Med 2013; 7(3):213-230. 12. Guttman O, Baranovski BM, Schuster R, et al. Acute-phase protein alpha1-anti-trypsin: Diverting injurious innate and adaptive immune responses from non-authentic threats. Clin Exp Immunol 2015;179(2):161-172. 13. Hayes VM, Gardiner-Garden M. Are polymorphic markers within the alpha-1-antitrypsin gene associated with risk of human immunodeficiency virus disease? J Infect Dis 2003; 188(8):1205-1208. 14. Adedeji AL, Olawoye TL. Elevated Serum Alpha-1-Antitrypsin Concentration is Associated with HIV Disease Non-Progression. MOJ Immunol 2015; 2(3):1-5 15. Ferreira TC da S, Sampaio EP, Argañaraz GA, Gondim MVP, Shapiro L, Argañaraz ER. Increased prevalence of the alpha-1-antitrypsin (A1AT) deficiency-related S gene in patients infected with human immunodeficiency virus type 1. J Med Virol 2014; 86(1):23-29. 16. Bryan CL, Beard KS, Pott GB, Rahkola J, Gardner EM, Janoff EN SL. HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations. Clin Invest Med 2010; 33(6):E384-389. 17. Stephenson SE, Wilson CL, Crothers K, et al . Impact of HIV Infection on Alpha-1Antitrypsin in the Lung. Am J Physiol Lung Cell Mol Physiol 2018; 314(4):L583-L592. 18. Chan ED, Iseman MD. Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobavteriuim abscessus infection of macrophages. Scand J Infect Dis. 2007;39:690-6. 19. Thayan R, Huat TL, See LLC, et al. The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever. Trans R Soc Trop Med Hyg 2009;103 (4):413-419. 20. Kumar Y, Liang C, Bo Z, Rajapakse JC, Ooi EE, Tannenbaum SR. Serum Proteome and Cytokine Analysis in a Longitudinal Cohort of Adults with Primary Dengue Infection Reveals Predictive Markers of DHF 2012; 6(11):e1887. 21. Jadhav M, Nayak M, Kumar S, et al. Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers. Omi A J Integr Biol 2017; 21 (11):665-677. 22. Song SH, Han M, Choi YS, et al. Proteomic profiling of serum from patients with tuberculosis. Ann Lab Med 2014; 34(5):345-353. 23. Ray S, Renu D, Srivastava R, et al. Proteomic investigation of falciparum and vivax malaria for identification of surrogate protein markers. PLoS One 2012; 7(8):e41751. 24. Ray S, Patel SK, Venkatesh A, et al. Quantitative Proteomics Analysis of Plasmodium vivax Induced Alterations in Human Serum during the Acute and Convalescent Phases of Infection. Sci Rep 2017; 7(1):4400. 25. De Groote MA, Nahid P, Jarlsberg L, et al. Elucidating Novel Serum Biomarkers Associated with Pulmonary Tuberculosis Treatment. PLoS One 2013; 8(4):e61002. 26. Soundravally R, Agieshkumar B, Daisy M, Sherin J, Cleetus CC. Ferritin levels predict severe dengue. Infection 2015; 43(1):13-19. 27. Kassa FA, Shio MT, Bellemare MJ, Faye B, Ndao M, Olivier M. New inflammation-related biomarkers during malaria infection. PLoS One 2011; 6(10):e26495. 28. Munch J, Ständker L, Adermann K, et al. Discovery and Optimization of a Natural HIV-1 Entry Inhibitor Targeting the gp41 Fusion Peptide. Cell 2007; 129(2):263-275. 29. Zhou X, Liu Z, Zhang J, Adelsberger JW, Yang J, Burton GF. Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4+ T lymphocytes. BMC Microbiol 2016; 16(1):172. 30. Watanabe M, Hirano A, Stenglein S, Nelson J, Thomas G, Wong TC. Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious Measles virus. J Virol 1995; 69(5):3206-3210. 31. Jean F, Thomas L, Molloy SS, et al. A protein-based therapeutic for Human cytomegalovirus infection. Proc Natl Acad Sci 2000; 97(6): 2864-2869. 32. Lenz O, ter Meulen J, Klenk HD, Seidah NG, Garten W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc Natl Acad Sci U S A 2001; 98(22):12701-12705. 33 Maisa A, Ströher U, Klenk HD, Garten W, Strecker T. Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted α1- antitrypsin variants. PLoS Negl Trop Dis 2009; 3(6):e446. 34. Berman R, Jiang D, Wu Q, Chu HW. α1-Antitrypsin reduces Rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke. Int J Chron Obstruct Pulmon Dis. 2016; 11(1):1279-1286. 35. Jiang D, Berman R, Wu Q, Stevenson C, Chu HW. The Anti-inflammatory Effect of Alpha-1 Antitrypsin in Rhinovirus-infected human airway epithelial cells. J Clin Cell Immunol 2016; 7(6):1-17. 36. Pott GB, Beard KS, Bryan CL, Merrick DT, Shapiro L. Alpha-1 Antitrypsin Reduces Severity of Pseudomonas Pneumonia in Mice and Inhibits Epithelial Barrier Disruption and Pseudomonas Invasion of Respiratory Epithelial Cells. Front Public Heal 2013; 1:19. 37. Cantin AM, Woods DE. Proliferation in a Model of Chronic Pseudomonas aeruginosa Lung Infection. Am J Respir Crt Care Med. 1999; 160(19):1130-1135. 38. Jiang D, Persinger R, Wu Q, Gross A, Chu HW. α1-antitrypsin promotes SPLUNC1-mediated lung defense against Pseudomonas aeruginosa infection in mice. Respir Res 2013; 14:122. 39. Morihara K, Tsuzuki H, Oda K. Protease and Elastase of Pseudomonas aeruginosa : Inactivation of Human Plasma α1-Proteinase Inhibitor. Infect Immun 1979; 24(1):188-193. 40. Sponer M, Nick H, Schnebli H. Different Susceptibility of Elastaase Inhibitors to Inactivation by Proteinases from Staphylococcuus aureus and Pseudomonas aeruginosa. Biol Chem 1991; 372:963-970. 41. Padrines M, Bieth JG. Pseudomonas aerugionsa Elastase Does Not Inactivate α1-Proteinase Inhibitor in the Presence of Leukocyte Elastase. Infect Immun 1989; 57(12):3793-3797 42 Knappstein S, Ide T, Schmidt MA, et al. α 1 -Antitrypsin Binds to and Interferes with Functionality of EspB from Atypical and Typical Enteropathogenic Escherichia coli Strains. Infect Immun 2004; 72(8):4344-4350. 43. Jonigk D, Al-Omari M, Maegel L, et al. Anti-inflammatory and immunomodulatory properties of α1-antitrypsin without inhibition of elastase. Proc Natl Acad Sci 2013; 110(37):15007-15012. 44. Kaner Z, Ochayon DE, Shahaf G, et al. Acute phase protein α1-antitrypsin reduces the bacterial burden in mice by selective modulation of innate cell responses. J Infect Dis 2015; 211(9):1489-1498. 45. Hadzic R, Nita I, Tassidis H, Riesbeck K, Wingren AG, Janciauskiene S. α1-Antitrypsin inhibits Moraxella catarrhalis MID protein-induced tonsillar B cell proliferation and IL-6 release. Immunol Lett 2006; 102(2):141-147. 46. Forney JR, Yang S, Healey MC. Antagonistic Effect of Human Alpha-1-Antitrypsin on Excystation of Cryptosporidium parvum Oocysts. J Parasitol 1996; 83(4):771-774 47. Forney JR, Yang S, Healey MC. Synergistic anticryptosporidial potential of the combination alpha-1- antitrypsin and paromomycin. Antimicrob Agents Chemother 1997; 41(9):2006-2008. 48. Conlan JW, Williams A AE. Inactivation of Human α-1-Antitrypsin by a Tissue-destructive Protease of LegioneIla pneumophila. J Gen Microbiol 1988;134:481-487. 49. Molla A, Matsumoto K, Oyamada I, Katsuki T MH. Degradation of Protease Inhibitors, Immunoglobulins, and Other Serum Proteins by Serratia Protease and Its Toxicity to Fibroblasts in Culture. Infect Immun 1986; 53(3):522-529. 50. Peterson KM, Alderete JF. Acquisition of aL-Antitrypsin by a Pathogenic Strain of Trichomonas vaginalis. Infect Immun 1983; 40(2):640-46. 51. Heusipp G, Spekker K, Brast S, Fälker S, Schmidt MA. YopM of Yersinia enterocolitica specifically interacts with α1-antitrypsin without affecting the anti-protease activity. Microbiology 2006; 152(5):1327-1335.