Assessment of Ceruloplasmin, Hemopexin, and Haptoglobin in Asthmatic Children
DOI:
https://doi.org/10.3889/oamjms.2020.3728Keywords:
Iron homeostasis, Biological markers, Asthma pathogenesisAbstract
BACKGROUND: Ceruloplasmin (Cp), haptoglobin, and hemopexin play a role in iron homeostasis and may function to modulate the systemic inflammatory response and be involved in tissue repair. We hypothesized that these proteins could be biological markers for bronchial asthma that reflect the involvement of iron oxidative stress in asthma pathogenesis.
AIM: Evaluation of serum levels of proteins involved in iron homeostasis (Cp, hemopexin, and haptoglobin) in asthmatic children and their correlation to pulmonary functions.
MATERIALS AND METHODS: Sixty moderate to severe persistent asthmatic children aged 6–13 years were included (30 during attacks and 30 in-between attacks). Thirty healthy matched controls were also recruited. All children were subjected to history taking, clinical evaluation and assessment of complete blood picture, serum levels of Cp, haptoglobin, hemopexin, and total IgE. Pulmonary function tests were assessed for all patients.
RESULTS: Serum Cp and haptoglobin were significantly elevated in asthmatic children between attacks (448.04 ± 386.79), (993.33 ± 554.56) compared to controls (168.42 ± 13.46), (473.33 ± 350.3), (p = 0.0002, p < 0.0001) and to asthmatics during exacerbations (288.8 ± 219.6), (620 ± 467.86), (p = 0.014, p = 0.006). Serum hemopexin was significantly higher in asthmatics between attacks (509.33 ± 341.51) compared to controls (296.67 ± 158.38) (p < 0.003) but no significant difference compared to acute exacerbations (477.33 ± 396.6). No significant correlations were found between any of the assessed protein levels and pulmonary functions. Hemoglobin concentration was significantly higher among stable asthmatics compared to acute exacerbation and control groups.
CONCLUSION: Cp, haptoglobin, and hemopexin can be used as a panel of non-invasive biomarkers that reflect the involvement of iron oxidative stress in asthma pathogenesis.
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References
World Health Organization. Asthma Key Facts. Geneva: World Health Organization. Available from: https://www.who.int/respiratory/asthma/en.
D’Amato G, Salzillo A, Piccolo A, D’Amato M, Liccardi G. A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma. Ther Clin Risk Manag. 2007;3(4):613-9. https://doi.org/10.2174/1568010043343615 PMid:18472983
Wenzel SE. Asthma: Defining of the persistent adult phenotypes. Lancet. 2006;368(9537):804-13. https://doi.org/10.1016/s0140-6736(06)69290-8 PMid:16935691
Uwaezuoke SN, Ayuk AC, Eze JN. Severe bronchial asthma in children: A review of novel biomarkers used as predictors of the disease. J Asthma Allergy. 2018;11:11-8. https://doi.org/10.2147/jaa.s149577 PMid:29398922
Wadsworth S, Sin D, Dorscheid D. Clinical update on the use of biomarkers of airway inflammation in the management of asthma. J Asthma Allergy. 2011;4:77-86. https://doi.org/10.2147/jaa.s15081 PMid:21792321
Mumby S, Chung KF, McCreanor JE, Moloney ED, Griffiths MJ, Quinlan GJ. Pro-oxidant iron in exhaled breath condensate: A potential excretory mechanism. Respir Med. 2011;105(9):1290-5. https://doi.org/10.1016/j.rmed.2011.03.021 PMid:21514132
Verrills NM, Irwin JA, He XY, Wood LG, Powell H, Simpson JL, et al. Identification of novel diagnostic biomarkers for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183(12):1633-43. https://doi.org/10.1164/rccm.201010-1623oc PMid:21471098
Fink MP. Editorial: Hemopexin: Newest member of the anti-inflammatory mediator club. J Leukoc Biol. 2009;86(2):203-4. https://doi.org/10.1189/jlb.0309137 PMid:19643739
Vassiliev V, Harris ZL, Zatta P. Ceruloplasmin in neurodegenerative diseases. Brain Res Brain Res Rev. 2005;49(3):633-40. https://doi.org/10.1016/j.brainresrev.2005.03.003 PMid:16269323
Lin T, Kwak YH, Sammy F, He P, Thundivalappil S, Sun G, et al. Synergistic inflammation is induced by blood degradation products with microbial toll-like receptor agonists and is blocked by hemopexin. J Infect Dis. 2010;202(4):624-32. https://doi.org/10.1086/654929 PMid:20617898
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. United States: Global Initiative for Asthma; 2012.
Cox DW, Tümer Z, Roberts EA. Copper transport disorders: Wilson disease and Menkes disease. In: Fernandes J, Saudubray JM, Van den Berghe G., editors. Inborn Metabolic Diseases. Berlin, Heidelberg: Springer; 2000. p. 384-91. https://doi.org/10.1007/978-3-662-04285-4_33
Wiggins JE, Goyal M, Wharram BL, Wiggins RC. Antioxidant ceruloplasmin is expressed by glomerular parietal epithelial cells and secreted into urine in association with glomerular aging and high-calorie diet. J Am Soc Nephrol. 2006;17(5):1382-7. https://doi.org/10.1681/asn.2005111239 PMid:16597684.
Baker CS, Evans TW, Haslam PL. Measurement of ceruloplasmin in the lungs of patients with acute respiratory distress syndrome: Is plasma or local production the major source? Respiration. 2000;67(5):533-8. https://doi.org/10.1159/000067469 PMid:11070458
Ermis B, Armutcu F, Gurel A, Kart L, Demircan N, Altin R, Demirel F. Trace elements status in children with bronchial asthma. Eur J Gen Med. 2004;1(1):4-8. https://doi.org/10.29333/ejgm/81766
Vural H, Uzun K. Serum and red blood cell antioxidant status in patients with bronchial asthma. Can Respir J. 2000;7(6):476-80. https://doi.org/10.1155/2000/907478 PMid:11121092
Farkhutdinov UR, Farkhutdinov SU. Efficacy of ceruloplasmin in patients with asthma. Ter Arkh. 2012;84(12):45-8. PMid:23479988
Van Rensen EL, Hiemstra PS, Rabe KF, Sterk PJ. Assessment of microvascular leakage via sputum induction: The role of substance P and neurokinin A in patients with asthma. Am J Respir Crit Care Med. 2002;165(9):1275-9. https://doi.org/10.1164/rccm.2110092 PMid:11991878
Yang F, Ghio AJ, Herbert DC, Weaker FJ, Walter CA, Coalson JJ. Pulmonary expression of the human haptoglobin gene. Am J Respir Cell Mol Biol. 2000;23(3):277-82. https://doi.org/10.1165/ajrcmb.23.3.4069 PMid:10970816
Kauffmann F, Frette C, Annesi I, Oryszczyn MP, Dore MF, Neukirch F. Relationships of haptoglobin level to FEV1, wheezing, bronchial hyper-responsiveness and allergy. Clin Exp Allergy. 1991;21(6):669-74. https://doi.org/10.1111/j.1365-2222.1991.tb03194.x PMid:1777829
Nishioka T, Uchida K, Meno K, Ishii T, Aoki T, Imada Y, et al. Alpha-1-antitrypsin and complement component C7 are involved in asthma exacerbation. Proteomics Clin Appl. 2008;2(1):46-54. https://doi.org/10.1002/prca.200780065 PMid:21136778
Larsen K, Macleod D, Nihlberg K, Gürcan E, Bjermer L, Marko-Varga G, et al. Specific haptoglobin expression in bronchoalveolar lavage during differentiation of circulating fibroblast progenitor cells in mild asthma. J Proteome Res. 2006;5(6):1479-83. https://doi.org/10.1021/pr050462h PMid:16739999.
Lamoureux A, Leclere M, Lemos K, Lefebvre J, Wagner B, Lavoie J. Systemic inflammation is present in both remission and clinical exacerbation in an equine model of severe asthma. Am J Resp Critic Care Med. 2011;183:A1322. https://doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1322
Kim CK, Chung CY, Koh YY. Changes in serum haptoglobin level after allergen challenge test in asthmatic children. Allergy 1998;53(2):184-9. https://doi.org/10.1111/j.1398-9995.1998.tb03868.x PMid:9534918
Koh YY, Kim YW, Park JD, Oh JW. A comparison of serum haptoglobin levels between acute exacerbation and clinical remission in asthma. Clin Exp Allergy 1996;26(10):1202-9. https://doi.org/10.1111/j.1365-2222.1996.tb00509.x PMid:8911708
Fröhlander N, Stjernberg N. Association between haptoglobin groups and hereditary predisposition for bronchial asthma. Hum Hered 1989;39(1):7-11. https://doi.org/10.1159/000153824 PMid:2474487
Krasteva A, Perenovska P, Ivanova A, Altankova I, Bocheva T, Kisselova A. Alteration in salivary components of children with allergic asthma. Biotechnol Biotechnol Equip. 2010;24(2):1866-9. https://doi.org/10.2478/v10133-010-0050-2
Sadrzadeh SM, Bozorgmehr J. Haptoglobin phenotypes in health and disorders. Am J Clin Pathol. 2004;121(Suppl):S97-104. https://doi.org/10.1309/8glx5798y5xhq0vw PMid:15298155
Haenen S, Clynen E, De Vooght V, Schoofs L, Nemery B, Hoet PH, et al. Proteome changes in auricular lymph nodes and serum after dermal sensitization to toluene diisocyanate in mice. Proteomics. 2012;12:3548-58. https://doi.org/10.1002/pmic.201200264 PMid:23038679
Monferran S, Paupert J, Dauvillier S, Salles B, Muller C. The membrane form of the DNA repair protein Ku interacts at the cell surface with metalloproteinase 9. EMBO J. 2004;23:3758-68. https://doi.org/10.1038/sj.emboj.7600403 PMid:15385961
Araujo BB, Dolhnikoff M, Silva LF, Elliot J, Lindeman JH, Ferreira DS, et al. Extracellular matrix components and regulators in the airway smooth muscle in asthma. Eur Respir J. 2008;32(1):61-9. https://doi.org/10.1183/09031936.00147807 PMid:18321931
Mak JC, Ho SP, Ho AS, Law BK, Cheung AH, Ho JC, et al. Sustained elevation of systemic oxidative stress and inflammation in exacerbation and remission of asthma. ISRN Allergy. 2013;2013:5618-31. https://doi.org/10.1155/2013/561831 PMid:24073339
Hussein A, Abdel Aziz S, Ahmed A. Imbalance between serum matrix metalloproteinase-9 and its inhibitor is associated with increased airway wall thickness in uncontrolled asthmatics. Egypt J Bronchol. 2012;6(1):37-43.
Muller-Eberhard U, Javid J, Liem HH, Hanstein A, Hanna M. Plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases. Blood. 1968;32(5):811-5. https://doi.org/10.1182/blood.v32.5.811.811 PMid:5687939
Nielsen MJ, Moestrup SK. Receptor targeting of hemoglobin mediated by the haptoglobins: Roles beyond heme scavenging. Blood. 2009;114(4):764-71. https://doi.org/10.1182/blood-2009-01-198309 PMid:19380867
Morello N, Tonoli E, Logrand F, Fiorito V, Fagoonee S, Turco E, et al. Haemopexin affects iron distribution and ferritin expression in mouse brain. J Cell Mol Med. 2009;13(10):4192-204. https://doi.org/10.1111/j.1582-4934.2008.00611.x PMid:19120692
Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharmacol. 2005;202(2):199-211. PMid:15629195
Lee SH, Kim KH, Kim JM, Yoon SH, Kim TH, Park SW, et al. Relationship between group-specific component protein and the development of asthma. Am J Respir Crit Care Med. 2011;184:528-36. https://doi.org/10.1164/rccm.201006-0951oc PMid:21169467.
Galez D, Dodig S, Raos M, Nogalo B. C-reactive protein in children with asthma and allergic rhinitis. Biochem Med. 2006;16(2):163-9. https://doi.org/10.11613/bm.2006.015
Razi E, Ehteram H, Akbari H, Chavoshi V, Razi A. Evaluation of high-sensitivity C-reactive protein in acute asthma. Tanaffos. 2012;11(1):32-7. PMid:25191398
Belda J, Margarit G, MartÃnez C, Casan P, RodrÃguez-Jerez F, Brufal M, et al. Bronchial exudate of serum proteins during asthma attack. Arch Bronconeumol 2005;41(6):328-33. https://doi.org/10.1016/s1579-2129(06)60232-2 PMid:15989890
Büyüköztürk S, Gelincik AA, Genç S, Koçak H, Oneriyidogan Y, Erden S, et al. Acute phase reactants in allergic airway disease. Tohoku J Exp Med. 2004;204:209-13. https://doi.org/10.1620/tjem.204.209 PMid:15502420
Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T. The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol. 2002;89(4):381-5. https://doi.org/10.1016/s1081-1206(10)62039-x PMid:12392382
Adams BK, Cydulka RK. Asthma evaluation and management. Emerg Med Clin North Am 2003;21(2):315-30. PMid:12793616
Weiss EB, Desforges JF. Oxyhemoglobin affinity in bronchial asthma: Chronic stable state, acute, and status asthmaticus. Chest. 1972;62(6):709-16. https://doi.org/10.1378/chest.62.6.709 PMid:4635420.
Guo CH, Liu PJ, Lin KP, Chen PC. Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: An open-label pilot study. Altern Med Rev. 2012;17(1):42-56. PMid:22502622
Hailemaryam T, Adissu W, Gedefaw L, Asres Y. Hematological profiles among asthmatic patients in Southwest Ethiopia: A comparative cross-sectional study. Hematol Transfus Int J. 2018;6(2):77-82. https://doi.org/10.15406/htij.2018.06.00157
Ejaz S, Nasim F, Ashraf M, Ahmad S. Hematological and biochemical profile of patients suffering from non-atopic asthma. Insights Chest Dis. 2017;2:2. https://doi.org/10.21767/2577-0578.10006
Ge RL, Witkowski S, Zhang Y, Alfrey C, Sivieri M, Karlsen T, et al. Determinants of erythropoietin release in response to short-term hypobaric hypoxia. J Appl Physiol (1985). 2002;92:2361-7. https://doi.org/10.1152/japplphysiol.00684.2001 PMid:12015348
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Copyright (c) 2020 Amany M. Abd Al-Aziz, Hala Shaaban, Ahmed Talaat, Mona A. M. Awad, Radwa Ali, Walaa A. Shahin (Author)
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