Correlation of α1-Antitrypsin (A1AT), Complement Component C5a and Secretory Immunoglobulin A (sIgA) With Pulmonary Complications; 20 Years After Sulfur Mustard Exposure, Sardasht-Iran Cohort Study

Document Type : Original Article

Authors

Immunoregulation Research Center, Shahed University, Tehran, Iran.

Abstract

Background: Little is known about pulmonary complications induced by Sulfur Mustard (SM), as a chemical warfare agent, especially considering its long term effects. The present study was carried out to investigate the association of α1-Antitrypsin (A1AT), Complement component C5a, and Secretory Immunoglobulin A (sIgA) with long-term pulmonary complications on SM-exposed individuals, 20 years after the exposure.
Materials and Methods: Sardasht-Iran Cohort Study (SICS) is a historical cohort study on 372 SM-exposed individuals and 128 age-matched unexposed participants. The clinical evaluations and Spirometry were performed on all the participants according to American Thoracic Society Criteria. Also, we assessed the salivary levels of A1AT, C5a, and sIgA using ELISA assay.
Results: The results indicated significant associations between salivary levels of A1AT, C5a, and sIgA with chronic cough in the exposed victims. Also, there were associations between C5a and sIgA with dyspnea in SM-exposed victims with chronic cough compared with those in the exposed victims without chronic cough. The salivary levels of C5a significantly decreased in severe pulmonary involvement. Moreover, a significant relationship was observed between the salivary levels of C5a and pulmonary function testes.
Conclusion: According to the findings, the salivary level of C5a might reflect the severity of pulmonary involvements following SM exposure. A1AT, as a protective agent, has correlations with cough and dyspnea. Although no strong correlation was found between the salivary levels of these factors with persistence of pulmonary complications, they can be effective in the development and progression of pathological changes in the lungs of the SM-exposed victims.

Keywords


Ghasemi H, Owlia P, Jalali Nadoushan MR, Pourfarzam S, Azimi G, Yarmohammadi ME, et al. A clinicopathological approach to sulfur mustard-induced organ complications: a major review. Cutaneous and ocular toxicology. 2013;32(4):304-24. [DOI:10.3109/15569527.2013.78161] [PMID]
Ghanei M, Tazelaar HD, Chilosi M, Harandi AA, Peyman M, Akbari HMH, et al. An international collaborative pathologic study of surgical lung biopsies from mustard gas-exposed patients. Respiratory medicine. 2008; 102(6):825-30. [DOI:10.1016/j.rmed.2008.01.016] [PMID]
Pourfarzam S, Yaraee R, Hassan ZM, Yarmohammadi ME, Faghihzadeh S, Soroush MR, et al. Chemokines, MMP-9 and PMN elastase in spontaneous sputum of sulfur mustard exposed civilians: Sardasht-Iran Cohort Study. International Immunopharmacology. 2013; 17(3):958-63. [DOI:10.1016/j.intimp.2012.12.015] [PMID]
Polosukhin VV, Cates JM, Lawson WE, Zaynagetdinov R, Milstone AP, Massion PP, et al. Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2012 ;184(3). [DOI:10.1164/rccm.201010-1629OC] [PMID] [PMCID]
Pilette C, Godding V, Kiss R, Delos M, Verbeken E, Decaestecker C, et al. Reduced epithelial expression of secretory component in small airways correlates with airflow obstruction in chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2001;163(1):185-94. [DOI:10.1164/ajrccm.163.1.9912137] [PMID]
Lockett AD, Kimani S, Ddungu G, Wrenger S, Tuder RM, Janciauskiene SM, et al. α1-Antitrypsin Modulates Lung Endothelial Cell Inflammatory Responses to TNF-α. American journal of respiratory cell and molecular biology. 2013; 49(1):143-50. [DOI:10.1165/rcmb.2012-0515OC] [PMID] [PMCID]
Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Köhnlein T, Welte T. The discovery of α1-antitrypsin and its role in health and disease. Respiratory medicine. 2011; 105(8):1129-39. [DOI:10.1016/j.rmed.2011.02.002] [PMID]
Liu D, Jiang T, Wang S, Cao X. Effect of hyperoxia on pulmonary SIgA and its components, IgA and SC. Journal of clinical immunology. 2013; 33(5):1009-17. [DOI:10.1007/s10875-013-9891-4] [PMID] [PMCID]
Janciauskiene S, Wrenger S, Welte T. Immunoregulatory Properties of Acute Phase Proteins—Specific Focus on α1-Antitrypsin; 2013.
Petrache I, Fijalkowska I, Zhen L, Medler TR, Brown E, Cruz P, et al. A novel antiapoptotic role for α1-antitrypsin in the prevention of pulmonary emphysema. American journal of respiratory and critical care medicine. 2006; 173(11):1222-8. [DOI:10.1164/rccm.200512-1842OC] [PMID] [PMCID]
Yarmohammadi ME, Hassan ZM, Mostafaie A, Ebtekar M, Yaraee R, Pourfarzam S, et al. Salivary levels of secretary IgA, C5a and alpha 1-antitrypsin in sulfur mustard exposed patients 20years after the exposure, Sardasht-Iran Cohort Study (SICS). International Immunopharmacology. 2013; 17(3):952-7. [DOI:10.1016/j.intimp.2012.12.021] [PMID]
Marc M, Kristan S, Rozman A, Kern I, Flezar M, Kosnik M, et al. Complement factor C5a in acute exacerbation of chronic obstructive pulmonary disease. Scandinavian journal of immunology. 2010;71(5):386-91. [DOI:10.1111/j.1365-3083.2010.02385.x] [PMID]
Marc MM, Korosec P, Kosnik M, Kern I, Flezar M, Suskovic S, et al. Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma. American journal of respiratory cell and molecular biology. 2004; 31(2):216-9. [DOI:10.1165/rcmb.2003-0394OC] [PMID]
Ghazanfari T, Faghihzadeh S, Aragizadeh H, Soroush MR, Yaraee R, Mohammad Hassan Z, et al. Sardasht-Iran cohort study of chemical warfare victims: design and methods. Arch Iran Med. 2009; 12(1):5-14. [PMID]
Razavi SM, Ghanei M, Salamati P, Safiabadi M. Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: A review. Chinese Journal of Traumatology. 2013; 16(3):163-8. [PMID]
Ghanei M, Harandi AA. Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: A review. Inhalation Toxicology. 2011; 23(7):363-71. [DOI:10.3109/08958378.2011.576278] [PMID]
Yaraee R, Ghazanfari T, Ebtekar M, Ardestani SK, Rezaei A, Kariminia A, et al. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study. International immunopharmacology. 2009; 9(13):1466-70. [DOI:10.1016/j.intimp.2009.09.001] [PMID]
Pourfarzam S, Ghazanfari T, Yaraee R, Ghasemi H, Hassan ZM, Faghihzadeh S, et al. Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by sulfur mustard: Sardasht-Iran Cohort Study. International Immunopharmacology. 2009; 9(13):1482-8. [DOI:10.1016/j.intimp.2009.09.002] [PMID]
Ghazanfari T, Sharifnia Z, Yaraee R, Pourfarzam S, Kariminia A, Mahlojirad M, et al. Serum soluble Fas ligand and nitric oxide in long-term pulmonary complications induced by sulfur mustard: Sardasht-Iran cohort study. International Immunopharmacology. 2009; 9(13):1489-93. [DOI:10.1016/j.intimp.2009.08.019] [PMID]
Ghazanfari Z, Ghazanfari T, Kermani-Jalilvand A, Yaraee R, Vaez-Mahdavi MR, Foroutan A, et al. Association of physical activity and IL-10 levels 20 years after sulfur mustard exposure: Sardasht-Iran cohort study. International Immunopharmacology. 2009; 9(13):1504-8. [DOI:10.1016/j.intimp.2009.08.025] [PMID]
Pott GB, Chan ED, Dinarello CA, Shapiro L. α-1-Antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood. Journal of Leukocyte Biology. 2009;85(5):886-95. [DOI:10.1189/jlb.0208145] [PMID] [PMCID]
Tuder RM, Janciauskiene SM, Petrache I. Lung disease associated with α1-antitrypsin deficiency. Proceedings of the American Thoracic Society. 2010; 7(6):381-6. [DOI:10.1513/pats.201002-020AW] [PMID] [PMCID]
Barnes PJ, Drazen JeM, Rennard SI, omson NCT. Asthma and COPDSecond; 2009.
Pourfarzam S, Ghazanfari T, Merasizadeh J, Ghanei M, Azimi G, Araghizadeh H, et al. Long-term pulmonary complications in sulfur mustard victims of Sardasht, Iran. Toxin Reviews. 2009; 28(1):8-13. [DOI:10.1080/15569540802689220]
Vojdani A, Kashanian A, Vojdani E, Campbell AW. Saliva secretory IgA antibodies against molds and mycotoxins in patients exposed to toxigenic fungi. Immunopharmacology and immunotoxicology. 2003; 25(4):595-614. [DOI:10.1081/IPH-120026444] [PMID]
Pilette C, Durham SR, Vaerman J-P, Sibille Y. Mucosal immunity in asthma and chronic obstructive pulmonary disease: a role for immunoglobulin A? Proceedings of the American Thoracic Society. 2004; 1(2):125-35. [DOI:10.1513/pats.2306032] [PMID]
Guo RF, Ward PA. Role of C5a in inflammatory responses. Annu Rev Immunol. 2005; 23:821-52. [DOI:10.1146/annurev.immunol.23.021704.115835] [PMID]
Shushakova N, Skokowa J, Schulman J, Baumann U, Zwirner J, Schmidt RE, et al. C5a anaphylatoxin is a major regulator of activating versus inhibitory FcγRs in immune complex–induced lung disease. The Journal of Clinical inVestigation. 2002; 110(12):1823-30. [DOI:10.1172/JCI16577] [PMID] [PMCID]
Strunk RC, Eidlen DM, Mason RJ. Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways. Journal of Clinical Investigation. 1988;81(5):1419. [DOI:10.1172/JCI113472] [PMID] [PMCID]