Abstract
Background: Previous studies have shown that macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of asthma. This study aimed to investigate whether serum MIF reflects a therapeutic response in allergic asthma. Methods: We enrolled 30 asthmatic patients with mild-to-moderate exacerbations and 20 healthy controls, analyzing the parameter levels of serum MIF, serum total immunoglobulin E (tIgE), peripheral blood eosinophil percentage (EOS%), and fractional exhaled nitric oxide (FeNO). Lung function indices were used to identify disease severity and therapeutic response. Results: Our study showed that all measured parameters in patients were at higher levels than those of controls. After one week of treatment, most parameter levels decreased significantly except for serum tIgE. Furthermore, we found that serum MIF positively correlated with EOS% as well as FeNO, but negatively correlated with lung function indices. Receiver operator characteristic (ROC) curve analysis indicated that among the parameters, serum MIF exhibited a higher capacity to evaluate therapeutic response. The area under the curve (AUC) of MIF was 0.931, with a sensitivity of 0.967 and a specificity of 0.800. Conclusions: Our results suggested that serum MIF may serve as a potential biomarker for evaluating therapeutic response in allergic asthma with mild-to-moderate exacerbations.
Abstract
目的
探讨血清巨噬细胞移动抑制因子在过敏性哮喘治疗反应评估中的应用价值。
创新点
采用血清巨噬细胞移动抑制因子评估过敏性哮喘的治疗反应。
方法
我们纳入了过敏性哮喘轻中度急性发作患者30例, 并以20例健康人为对照, 分别检测和分析了治疗前后患者以及健康人的血清巨噬细胞移动抑制因子, 总免疫球蛋白E (总IgE), 外周血嗜酸性粒细胞百分数和呼出气一氧化氮等指标, 同时进行肺功能检查以监测患者的治疗反应。
结论
血清巨噬细胞移动抑制因子作为一种潜在的生物标志物, 可用于评估过敏性哮喘轻中度急性发作患者的治疗反应。
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agrawal DK, Shao ZF, 2010. Pathogenesis of allergic airway inflammation. Curr Allergy Asthma Rep, 10(1):39–48. https://doi.org/10.1007/s11882-009-0081-7
Al-Abed Y, VanPatten S, 2011. MIF as a disease target: ISO-1 as a proof-of-concept therapeutic. Future Med Chem, 3(1):45–63. https://doi.org/10.4155/fmc.10.281
Amano T, Nishihira J, Miki I, 2007. Blockade of macrophage migration inhibitory factor (MIF) prevents the antigen-induced response in a murine model of allergic airway inflammation. Inflamm Res, 56(1):24–31. https://doi.org/10.1007/s00011-007-5184-9
ATS/ERS (American Thoracic Society, European Respiratory Society), 2005. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med, 171(8):912–930. https://doi.org/10.1164/rccm.200406-710ST
Bar-Yishay E, Amirav I, Goldberg S, 2003. Comparison of maximal midexpiratory flow rate and forced expiratory flow at 50% of vital capacity in children. Chest, 123(3): 731–735. https://doi.org/10.1378/chest1233.731
Bernhagen J, Calandra T, Mitchell RA, et al., 1993. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature, 365(6448):756–759. https://doi.org/10.1038/365756a0
Bloom BR, Bennett B, 1966. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science, 153(3731):80–82. https://doi.org/10.1126/science.153.3731.80
Bozza MT, Lintomen L, Kitoko JZ, et al., 2020. The role of MIF on eosinophil biology and eosinophilic inflammation. Clin Rev Allergy Immunol, 58(1):15–24. https://doi.org/10.1007/s12016-019-08726-z
Cai C, Yang J, Hu SP, et al., 2007. Relationship between urinary cysteinyl leukotriene E4 levels and clinical response to antileukotriene treatment in patients with asthma. Lung, 185(2):105–112. https://doi.org/10.1007/s00408-006-0001-8
Calandra T, Roger T, 2003. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol, 3(10):791–800. https://doi.org/10.1038/nri1200
Calandra T, Echtenacher B, le Roy D, et al., 2000. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med, 6(2):164–170. https://doi.org/10.1038/72262
Chen PF, Luo YL, Wang W, et al., 2010. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma. Mol Med, 16(9–10):400–408. https://doi.org/10.2119/molmed.2009.00128
Chung KF, Wenzel SE, Brozek JL, et al., 2014. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J, 43(2):343–373. https://doi.org/10.1183/09031936.00202013
Das R, Moss JE, Robinson E, et al., 2011. Role of macrophage migration inhibitory factor in the Th2 immune response to epicutaneous sensitization. J Clin Immunol, 31(4):666–680. https://doi.org/10.1007/s10875-011-9541-7
David JR, 1966. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA, 56(1):72–77. https://doi.org/10.1073/pnas.56.1.72
Dweik RA, Boggs PB, Erzurum SC, et al., 2011. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FeNO) for clinical applications. Am J Respir Crit Care Med, 184(5):602–615. https://doi.org/10.1164/rccm.9120-11ST
El-Adly TZ, Kamal S, Selim H, et al., 2016. Association of macrophage migration inhibitory factor promoter polymorphism −173G/C with susceptibility to childhood asthma. Cent Eur J Immunol, 41(3):268–272. https://doi.org/10.5114/ceji.2016.63126
Fitzpatrick AM, Gaston BM, Erzurum SC, et al., 2006. Features of severe asthma in school-age children: atopy and increased exhaled nitric oxide. J Allergy Clin Immunol, 118(6):1218–1225. https://doi.org/10.1016/j.jaci.2006.08.019
GINA (Global Initiative for Asthma), 2019. Global strategy for asthma management and prevention, 2019. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf
Kobayashi M, Nasuhara Y, Kamachi A, et al., 2006. Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats. Eur Respir J, 27(4):726–734. https://doi.org/10.1183/09031936.06.00107004
Lai KN, Leung JC, Metz CN, et al., 2003. Role for macrophage migration inhibitory factor in acute respiratory distress syndrome. J Pathol, 199(4):496–508. https://doi.org/10.1002/path.1291
Lang T, Foote A, Lee JPW, et al., 2015. MIF: implications in the pathoetiology of systemic lupus erythematosus. Front Immunol, 6:577. https://doi.org/10.3389/fimmu.2015.00577
Miller MR, Hankinson J, Brusasco V, et al., 2005. Standardisation of spirometry. Eur Respir J, 26(2):319–338. https://doi.org/10.1183/09031936.05.00034805
Mizue Y, Ghani S, Leng L, et al., 2005. Role for macrophage migration inhibitory factor in asthma. Proc Natl Acad Sci USA, 102(40):14410–14415. https://doi.org/10.1073/pnas.0507189102
Nishihira J, Ishibashi T, Fukushima T, et al., 2003. Macrophage migration inhibitory factor (MIF): its potential role in tumor growth and tumor-associated angiogenesis. Ann N Y Acad Sci, 995(1):171–182. https://doi.org/10.1111/j.1749-6632.2003.tb03220.x
Pellegrino R, Viegi G, Brusasco V, et al., 2005. Interpretative strategies for lung function tests. Eur Respir J, 26(5):948–968. https://doi.org/10.1183/09031936.05.00035205
Razi E, Moosavi GA, 2010. Serum total IgE levels and total eosinophil counts: relationship with treatment response in patients with acute asthma. J Bras Pneumol, 36(1):23–28. https://doi.org/10.1590/s1806-37132010000100006
Rossi AG, Haslett C, Hirani N, et al., 1998. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J Clin Invest, 101(12):2869–2874. https://doi.org/10.1172/JCI1524
Tan YQ, Cao LF, Shen J, et al., 2012. Climatic factors correlate with innate immune response in children with Dermatophagoides farinae-induced allergic asthma. J Int Med Res, 40(2):740–747. https://doi.org/10.1177/147323001204000239
To T, Stanojevic S, Moores G, et al., 2012. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health, 12:204. https://doi.org/10.1186/1471-2458-12-204
Wang B, Huang XZ, Wolters PJ, et al., 2006. Cutting edge: deficiency of macrophage migration inhibitory factor impairs murine airway allergic responses. J Immunol, 177(9):5779–5784. https://doi.org/10.4049/jimmunol.177.9.5779
Wu J, Fu S, Ren X, et al., 2009. Association of MIF promoter polymorphisms with childhood asthma in a northeastern Chinese population. Tissue Antigens, 73(4):302–306. https://doi.org/10.1111/j.1399-0039.2008.01206.x
Yamaguchi E, Nishihira J, Shimizu T, et al., 2000. Macrophage migration inhibitory factor (MIF) in bronchial asthma. Clin Exp Allergy, 30(9):1244–1249. https://doi.org/10.1046/j.1365-2222.2000.00888.x
Zernecke A, Bernhagen J, Weber C, 2008. Macrophage migration inhibitory factor in cardiovascular disease. Circulation, 117(12):1594–1602. https://doi.org/10.1161/CIRCULATIONAHA.107.729125
Zhang XY, Simpson JL, Powell H, et al., 2014. Full blood count parameters for the detection of asthma inflammatory phenotypes. Clin Exp Allergy, 44(9):1137–1145. https://doi.org/10.1111/cea.12345
Zhao ST, Wang CZ, 2018. Regulatory T cells and asthma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(9):663–673. https://doi.org/10.1631/jzus.B1700346
Acknowledgments
The study was supported by the Henan Province Medical Science and Technology Research Project (No. 2018020737), China.
Author information
Authors and Affiliations
Corresponding author
Additional information
Author contributions
Huiyuan ZHU and Shaochun YAN designed the study, wrote and edited the manuscript. Huiyuan ZHU performed the clinical and experimental research and data analysis. Zhong ZHANG, Xiaolin LI, Zheng LIU, Xing MA, Lina ZHOU, Lin ZHANG, Mingming FENG, Yiwei GENG, and Aixin ZHANG participated in the collection of clinical and experimental data. Aiguo XU, Jingshuo WU, and Sabina JANCIAUSKIENE coordinated the research project. All authors have read and approved the final manuscript, and therefore have full access to all the data in the study and take responsibility for the data’s integrity and security.
Compliance with ethics guidelines
Huiyuan ZHU, Shaochun YAN, Jingshuo WU, Zhong ZHANG, Xiaolin LI, Zheng LIU, Xing MA, Lina ZHOU, Lin ZHANG, Mingming FENG, Yiwei GENG, Aixin ZHANG, Sabina JANCIAUSKIENE, and Aiguo XU declare that they have no conflict of interest.
All procedures were conducted in accordance with the Helsinki Declaration of 1975, as revised in 2008 (5). The medical ethics committee of Zhengzhou Second People’s Hospital approved the study, and all participants signed the written informed consent.
Rights and permissions
About this article
Cite this article
Zhu, H., Yan, S., Wu, J. et al. Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study. J. Zhejiang Univ. Sci. B 22, 512–520 (2021). https://doi.org/10.1631/jzus.B2000555
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B2000555
Key words
- Macrophage migration inhibitory factor (MIF)
- Allergic asthma
- Eosinophilic inflammation
- Fractional exhaled nitric oxide
- Immunoglobulin E (IgE)