Circulating Serum Levels of Fox P3, GATA-3 and IL-17 A as Potential Biomarkers in Patients with Symptomatic Asthma
Abstract
Background: The lack of information on the association of certain factors in the pathophysiology of the chronic inflammatory disorder, Asthma limits its early detection and therapy. Keeping these facts in view, an endeavour was made to investigate the roles, if any, such as IL-17A, FoxP3 and GATA-3 in the occurrence and intensity of asthma in north Indian population.
Objective: The study was conducted to evaluate the level of FoxP3, GATA-3 and IL-17A in symptomatic asthma patients as compared to healthy controls.
Methods: In the study we had taken 125 cases and 125 controls. Levels of total interleukin 17A, transcription factors FoxP3 and GATA-3 were measured by ELISA in serum of asthmatic patients. Student’s T-test and ANOVA test was applied for quantitative variables. The qualitative variables analyzed using Chi-Square test /Fisher’s exact test.
Results: Clinical symptoms like breathlessness, cough, headache, disturbed sleep, congestion, and wheezing were found significantly elevated in asthmatics as compared to the controls. Except haemoglobin; in the cases the levels of blood eosinophils, Absolute Eosinophil Count (AEC), Total Leukocyte Count (TLC) and serum Immunoglobulin E (IgE) were observed higher as compared to the controls and also the higher serum levels of IL-17A and GATA-3 were found in the cases. Contrary to IL-17A and GATA-3; the levels of FoxP3 was increased in the control, and was lower in the patient serum. A positive correlation was found between total IgE and GATA-3 (Pearson Correlation=0.283, P=0.042). We have shown that GATA-3 is increased in the asthmatic patients (0.541±0.140) than in the controls (0.312±0.076). The GATA-3 was found over expressed in patients with severe asthma.
Conclusion: Increased level of GATA-3 and IL-17A might be useful as diagnostic marker for patients with symptomatic asthma there is need for further larger scale studies to establish the role of these biomarkers in asthmatic patients.
References
Boushey HA, Holtzman MJ, Sheller JR et al. Bronchial hyperreactivity. Am Rev Respir Dis 1980; 121(2): 389413.
Pal R, Dahal S, Pal S. Prevalence of bronchial asthma in Indian Children. Indian Journal of Community Medicine
; 34(4): 310-316.3. Kynyk JA, Mastronarde JG, McCallister JW. Asthma, the sex difference. Current Opinion in Pulmonary Medicine 2011; 17(1): 6-11.
Ling MF, Luster AD. Allergen-Specific CD41 T Cells in Human Asthma. The American Thoracic Society, 2016.
S25-S30.
Holgate ST, Polosa, R. Treatment strategies for allergy and asthma. Nat Rev Immunol 2008; 8: 218‑230.
Singh M, Agarwal A, Chatterjee B et al. Correlation of cutaneous sensitivity and cytokine response in children
with asthma. Lung India 2017; 34: 506-510.
Harrington LE, Mangan PR. Weaver CT. Expanding the effector CD4 T‑cell repertoire: The Th17 lineage. Curr
Opin Immunol 2006; 18(3): 349‑356.
Zhao Y, Yang J, Gao YD et al. Th17 Immunity in Patients with Allergic Asthma. Int Arch Allergy Immunol 2010;
(4): 297-307.
Shean JA, John FA. TH17 cells in asthma and inflammation. Biochimica et Biophysica Acta 2011;
: 1066-79.
Pierre MK, Vijay KK. Mechanisms of disease interleukin-17 and type 17 helper T Cells. The New
England J Med 2009; 361(9): 888-898.
Kim HY, DeKruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive
immunity. Nature Immunol 2010; 11(7): 577-584.
Doe C, Bafadhel M, Siddiqui S et al. Expression of the T helper 17-associated cytokines IL17-A and IL-17F in
asthma and COPD. Chest J 2010; 138(5): 1140-1147.
Kudo M, Melton AC, Chen C et al. IL-17A produced by alphabeta T cells drives airway hyper responsiveness in
mice and enhances mouse and human airway smooth muscle contraction. Nat Med 2012; 18(4): 547-554.
Meiler F, Zumkehr J, Klunker S et al. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen
exposure. J Exp Med 2008; 205(12): 2887-2898.
Bellinghausen I, Klostermann B, Knop J et al. Human CD41CD251T cells derived from the majority of atopic
donors are able to suppress TH1 and TH2 cytokine production. J Allergy Clin Immunol 2003; 111: 862-868.
Akdis M, Akdis CA. Therapeutic manipulation of immune tolerance in allergic disease. Nat Rev Drug
Discov 2009; 8(8): 645-660.
Pyzik M, Piccirillo CA. TGF-beta1 modulates FoxP3 expression and regulatory activity in distinct CD41 T
cell subsets. J Leukoc Biol 2007; 82(8): 335-346.
Trzonkowski P, Szmit E, Myoeliwska J et al. CD41CD251 T regulatory cells inhibit cytotoxic activity of CTL and
NK cells in humans – impact of immunosenescence. Clin Immunol. 2006; 119: 307-16.
Seroogy CM, Gern JE. The role of T regulatory cells in asthma. J Allergy Clin Immunol 2005; 116(5): 996-999.
Klunker S, Chong MM, Mantel PY et al. Transcription factors RUNX1 and RUNX3 in the induction and
suppressive function of FoxP31 inducible regulatory Tcells. J Exp Med 2009; 206(12): 2701-2715.
Broide DH. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling. J Allergy Clin Immunol. 2008; 121(3): 560-570.
Robinson DS. The role of the T cell in asthma. J Allergy Clin Immunol 2010; 126(6): 1081-1091.
Martinis M, Benedetto MC, Mengoli LP et al. Senile osteoporosis: is it an immune-mediated disease?
Inflamm Res 2006; 55(10): 399-404.
Mantel PY, Kuipers H, Boyman O et al. GATA-3-driven Th2 responses inhibit TGF-beta1-induced FOXP3
expression and the formation of regulatory Tcells. PLoS Biol 2007; 5(12): 2847-2861.
Alyasin S, Karimi MH, Amin R et al. Interleukin-17 gene expression and serum levels in children with severe
asthma. Iran J Immunol 2013; 10(3): 177-185.
Pascual RM, Peters SP. Airway remodeling contributes to the progressive loss of lung function in asthma: an
overview. J Allergy Clin Immunol 2005; 116(3): 477-486.
Jeffery P. Inflammation and remodeling in the adult and child with asthma. Pediatr Pulmonol 2001; 21: 3-16.
Hatta M, Surachmanto EE, Islam AA et al. Expression of mRNA IL‑17F and sIL‑17F in atopic asthma patients.
BMC Res Notes 2017; 10: 202.
Ramsey CD, Lazarus R, Camargo CA, et al. Polymorphisms in interleukin 17F gene (IL17F) and asthma. Genes
Immun. 2005; 6(3): 236-241.
Tello AV, Halwani R, Rui L et al. IL-17A and IL-17F expression in B lymphocytes. Int Arch Allergy Immunol
; 157: 406-416.
Ota K, Kawaguchi M, Matsukura S et al. Potential involvement of IL-17F in asthma. J Immunol Res 2014,
Article ID 602846, 8.
Trevor JL, Deshane JS. Refractory asthma: mechanisms, target, and therapy. Allergy 2014; 69(7): 817-827.
Piva SR, Fitzgerald K, Irrgang JJ et al. Reliability of measures of impairments associated with
patellofemoral pain syndrome. BMC Musculoskeletal Disorders 2016; 17: 208.
Mowahedi M, Samet M, Zare F et al. Serum Levels of IL-17A Increase in Asthma But Don’t Correlate with
Serum Level of IgE and Asthma Severity. Int J Med Lab 2015; 2(1): 25-33.
Iwakura Y, Nakae S, Saijo S et al. The roles of IL-17A in inflammatory immune responses and host defense
against pathogens. Immunol Rev 2008; 226: 57-79.
Yang XO, Chang SH, Park H et al. Regulation of inflammatory responses by IL-17F. J Exp Med 2008;
(5): 1063-1075.
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor FOXP3.Science 2003; 299(5609): 1057-1061.
Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated FOXP3
expression. Nature 2007; 445(7129): 766-770.
Karagiannidis C, Akdis M, Holopainen P et al. Glucocorticoids upregulate FOXP3 expression and
regulatory T cells in asthma. J Allergy Clin Immunol 2004; 114(6): 1425-1433.
Piccirillo CA, Letterio JJ, Thornton AM et al. CD4+CD25+can mediate suppressor function in the absence of
transforming growth factor beta-1 production and responsiveness. J Exp Med 2002; 196(2): 237-246.
Gemou-Engesaaeth V, Kay AB, Bush A et al. Activated peripheral blood CD4 and CD8 T lymphocyte in child
asthma: Correlation with eosinophilia and disease severity. Pediatr Allergy Immunol 1994; 5(3): 170-177.
Kagoshima M, Wilcke T, Ito K et al. Glucocorticoid mediated trans repression is regulated by histone
acetylation and DNA methylation. Eur J Pharmacol 2001; 429(1-3): 327-334.
Ray A, Cohn L. Th2 cells and GATA-3 in asthma: newinsights into the regulation of airway inflammation. J
Clin Invest 1999; 104(8): 985-993.
Winandy S, Brown M. No DL1 Notch ligand? GATA be a mast cell. Nat Immunol 2007; 8(8): 796-768.
Mjösberg J, Bernink J, Golebski K et al. The transcription factor GATA-3 is essential for the function of human
type 2 innate lymphoid cells. Immunity 2012; 37(4): 649-659.
Winandy S, Brown M. No DL1 Notch ligand? GATA be a mast cell. Nat Immunol 2007; 8: 796-798.
Sadat MA, Kumatori A, Suzuki S et al. GATA-3 represses gp91phox gene expression in eosinophil-committed
HL-60-C15 cells. FEBS Lett 1998; 436(3): 390-394.
Gauvreau GM, Boulet LP, Postma DS et al. Effect of low-dose ciclesonide on allergen-induced responses
in subjects with mild allergic asthma. J Allergy Clin Immunol 2005; 116: 285-291.
Bergqvist A, Andersson CK, Hoffmann HJ et al. Marked epithelial cell pathology and leukocyte paucity in
persistently symptomatic severe asthma. Am J Respir Crit Care Med 2013; 188: 1475-1477.
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