Glucocorticoid-induced Changes in the Transcriptional Activity of Genes of the Innate and Adaptive Immune System in the Blood of Patients with Acute Urticaria
DOI:
https://doi.org/10.3889/oamjms.2021.7545Keywords:
Acute urticarial, Glucocorticoids, mRNA, Innate and adaptive immune responsesAbstract
Background: A number of the main effects of glucocorticoids (GCs) are their direct action on T cells, mainly through the transcriptional regulation: elevated expression of immune-regulatory proteins, inhibitory receptors, and reduced expression of pro-inflammatory cytokines, co-stimulatory molecules, and cell cycle mediators. But controversies arise due to the clinical effectiveness of GCs in the treatment of acute urticaria.
Methods: In our research, we applied a pathway-specific PCR array (Human Innate & Adaptive Immune Responses RT2 Profiler PCR Array, QIAGEN, Germany) to detect and verify innate & adaptive immune responses pathway-focused genes expression in the blood of patients with acute urticaria who received treatment with glucocorticoids in addition to standard therapy.
Results: Adding glucocorticoids to standard therapy did not notably affect the nature of the clinical presentation of acute urticaria, which was assessed according to the UAS scale (urticaria activity score). Analysis of the transcriptional profile of peripheral blood mononuclear cells in patients with acute urticaria against the background of glucocorticoid therapy showed the induction expression of the FOXP3 and IL10 genes against the background of repression of the transcriptional activity of the genes for chemokines and cytokines CCL5, CXCL8, IFNG, IL2, IL5, IL17A, IL1B, and TNF. Glucocorticoid-induced changes in the transcriptome also manifested by pronounced repression in genes of CD40 and CD80 (B7-1) co-stimulatory molecules, transcriptional regulators of Th1-cells differentiation - TBX21 and STAT1, Th17 cells - RORC, NLRP3-inflammasome genes, and the transcription factor NFKB1 compared with the control group.
Conclusions: Adding glucocorticoids to the standard therapy of acute urticaria has a pronounced immunosuppressive potential at the transcriptome level of immune response genes in the blood; however, it does not have any noticeable clinical effect.
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Pier J, Bingemann TA. Urticaria, angioedema, and anaphylaxis. Pediatr Rev. 2020;41(6):283-92. http://doi.org/10.1542/pir.2019-0056 DOI: https://doi.org/10.1542/pir.2019-0056
Maurer M, Zuberbier T, Metz M. The classification, pathogenesis, diagnostic workup, and management of urticaria: An update. Handb Exp Pharmacol. 2021;2021:506. http://doi.org/10.1007/164_2021_506 DOI: https://doi.org/10.1007/164_2021_506
Khan DA, Kocatürk E, Bauer A, Aygören-Pürsün E. What’s new in the treatment of urticaria and angioedema. J Allergy Clin Immunol Pract. 2021;9(6):2170-84. http://doi.org/10.1016/j.jaip.2021.03.012 PMid:34112473 DOI: https://doi.org/10.1016/j.jaip.2021.03.012
Yiğit RE, Cavkaytar O, Besli GE, Arga M. Do pediatric emergency physicians comply with guideline recommendations in management of patients with acute urticaria? Pediatr Emerg Care. 2021;37(8):407-412. http://doi.org/10.1097/PEC.0000000000002327 PMid:34043307 DOI: https://doi.org/10.1097/PEC.0000000000002327
Zuberbier T, Aberer W, Asero R, Latiff AH, Baker D, Ballmer-Weber B, et al. The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-414. http://doi.org/10.1111/all.13397 PMid:29336054 DOI: https://doi.org/10.1111/all.13397
Taves MD, Ashwell JD. Glucocorticoids in T cell development, differentiation and function. Nat Rev Immunol. 2021;21(4):233- 43. http://doi.org/10.1038/s41577-020-00464-0 PMid:33149283 DOI: https://doi.org/10.1038/s41577-020-00464-0
Barniol C, Dehours E, Mallet J, Houze-Cerfon CH, Lauque D, Charpentier S. Levocetirizine and prednisone are not superior to levocetirizine alone for the treatment of acute urticaria: A randomized double-blind clinical trial. Ann Emerg Med. 2018;71(1):125-31.e1. http://doi.org/10.1016/j.annemergmed.2017.03.006 PMid:28476259 DOI: https://doi.org/10.1016/j.annemergmed.2017.03.006
Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, et al. Short termuse of oral corticosteroids and related harms among adults in the United States: Population based cohort study. BMJ. 2017;357:j1415. http://doi.org/10.1136/bmj.j1415 PMid:28404617 DOI: https://doi.org/10.1136/bmj.j1415
Bilous I, Pavlovych L, Krynytska I, Marushchak M, Kamyshnyi A. Apoptosis and cell cycle pathway-focused genes expression analysis in patients with different forms of thyroid pathology. Open Access Maced J Med Sci. 2020;8(B):784-92. https://doi.org/10.3889/oamjms.2020.4760 DOI: https://doi.org/10.3889/oamjms.2020.4760
Bilous II, Korda MM, Krynytska IY, Kamyshnyi AM. Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis. Endocr Regul. 2020;54(2):109-18. https://doi.org/10.2478/enr-2020-0013 PMid:32597152 DOI: https://doi.org/10.2478/enr-2020-0013
Bilous II, Pavlovych LL, Kamyshnyi AM. Primary hypothyroidism and autoimmune thyroiditis alter the transcriptional activity of genes regulating neurogenesis in the blood of patients. Endocr Regul. 2021;55(1):5-15. https://doi.org/10.2478/enr-2021-0002 PMid:33600668 DOI: https://doi.org/10.2478/enr-2021-0002
Kamyshna II, Pavlovych LB, Maslyanko VA, Kamyshnyi AM. Analysis of the transcriptional activity of genes of neuropeptides and their receptors in the blood of patients with thyroid pathology. J Med Life. 2021;14(2):243-9. https://doi.org/10.25122/jml-2020-0183 PMid:34104248 DOI: https://doi.org/10.25122/jml-2020-0183
Kamyshna I, Kamyshnyi A. Transcriptional activity of neurotrophins genes and their receptors in the peripheral blood in patients with thyroid diseases in Bukovinian population of Ukraine. Open Access Maced J Med Sci. 2021;9(A):208-16. https://doi.org/10.3889/oamjms.2021.6037 DOI: https://doi.org/10.3889/oamjms.2021.6037
Kamyshna I, Pavlovych L, Kamyshnyi A. Association between serum brain-derived neurotrophic factor and 25-OH Vitamin D levels with Vitamin D receptors gene polymorphism (rs2228570) in patients with autoimmune thyroiditis and hypothyroidism. Open Access Maced J Med Sci. 2021;9(A):659-64. https://doi.org/10.3889/oamjms.2021.6631 DOI: https://doi.org/10.3889/oamjms.2021.6631
Kamyshna I, Pavlovych L, Malyk I, Kamyshnyi A. 25-OH Vitamin D blood serum linkage with VDR gene polymorphism (rs2228570) in thyroid pathology patients in the West-Ukrainian population. J Med Life. 2021;14(4):549-56. https://doi.org/10.25122/jml-2021-0101 PMid:34621381 DOI: https://doi.org/10.25122/jml-2021-0101
Putilin DA, Evchenko SY, Fedoniuk LY, Tokarskyy OS, Kamyshny OM, Migenko LM, et al. The influence of metformin to the transcriptional activity of the mTOR and FOX3 genes in parapancreatic adipose tissue of streptozotocin-induced diabetic rats. J Med Life. 2020;13(1):50-5. https://doi.org/10.25122/jml-2020-0029 PMid:32341701
Degen AS, Krynytska IY, Kamyshnyi AM. Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers. Endocr Regul. 2020;54(3):160-71. https://doi.org/10.2478/enr-2020-0019 Mid:32857721 DOI: https://doi.org/10.2478/enr-2020-0019
Nosulenko IS, Voskoboynik OY, Berest GG, Safronyuk SL, Kovalenko SI, Kamyshnyi OM, et al. Synthesis and antimicrobial activity of 6-thioxo-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]- quinazolin-2-one derivatives. Sci Pharm. 2014;82(3):483-500. https://doi.org/10.3797/scipharm.1402-10 PMid:25853063 DOI: https://doi.org/10.3797/scipharm.1402-10
Lyubomirskaya ES, Kamyshnyi AM, Krut YY, Smiianov VA, Fedoniuk LY, Romanyuk LB, et al. SNPs and transcriptional activity of genes of innate and adaptive immunity at the maternal-fetal interface in woman with preterm labour, associated with preterm premature rupture of membranes. Wiad Lek. 2020;73(1):25-30. PMid:32124801
Quatrini L, Ricci B, Ciancaglini C, Tumino N, Moretta L. Regulation of the immune system development by glucocorticoids and sex hormones. Front Immunol. 2021;12:672853. https://doi.org/10.3389/fimmu.2021.672853 PMid:34248954 DOI: https://doi.org/10.3389/fimmu.2021.672853
Shimba A, Ikuta K. Control of immunity by glucocorticoids in health and disease. Semin Immunopathol. 2020;42(6):669-80. https://doi.org/10.1007/s00281-020-00827-8 PMid:33219395 DOI: https://doi.org/10.1007/s00281-020-00827-8
Pollack CV Jr., Romano TJ. Outpatient management of acute urticaria: the role of prednisone. Ann Emerg Med. 1995;26(5):547-51. https://doi.org/10.1016/s0196-0644(95)70002-1 Mid:7486360 DOI: https://doi.org/10.1016/S0196-0644(95)70002-1
Losappio L, Heffler E, Bussolino C, Cannito CD, Carpentiere R, Raie A, et al. Acute urticaria presenting in the emergency room of a general hospital. Eur J Intern Med. 2014;25(2):147-50. https://doi.org/10.1016/j.ejim.2013.11.003 PMid:24275113 DOI: https://doi.org/10.1016/j.ejim.2013.11.003
Grunau BE, Wiens MO, Rowe BH, McKay R, Li J, Yi TW, et al. Emergency department corticosteroid use for allergy or anaphylaxis is not associated with decreased relapses. Ann Emerg Med. 2015;66(4):381-9. https://doi.org/10.1016/j.annemergmed.2015.03.003 PMid:25820033 DOI: https://doi.org/10.1016/j.annemergmed.2015.03.003
Arga M, Cavkaytar Ö, Emeksiz HC. A randomized controlled trial of adding intravenous corticosteroids to H1 antihistamines in patients with acute urticaria. Am J Emerg Med. 2021;45:592- 3. https://doi.org/10.1016/j.ajem.2020.12.038 DOI: https://doi.org/10.1016/j.ajem.2020.12.038
Javaud N, Soria A, Maignan M, Martin L, Descamps V, Fain O, et al. Glucocorticoids for acute urticaria: Study protocol for a double-blind non-inferiority randomised controlled trial. BMJ Open. 2019;9(8):e027431. https://doi.org/10.1136/bmjopen-2018-027431 PMid:31439599 DOI: https://doi.org/10.1136/bmjopen-2018-027431
Tian J, Zhang B, Rui K, Wang S. The role of GITR/GITRL Interaction in autoimmune diseases. Front Immunol. 2020;11:588682. https://doi.org/10.3389/fimmu.2020.588682 PMid:33163004 DOI: https://doi.org/10.3389/fimmu.2020.588682
Motavalli R, Majidi T, Pourlak T, Abediazar S, Shoja MM, Vahed SZ, et al. The clinical significance of the glucocorticoid receptors: Genetics and epigenetics. J Steroid Biochem Mol Biol. 2021;213:105952. https://doi.org/10.1016/j.jsbmb.2021.105952 PMid:34274458 DOI: https://doi.org/10.1016/j.jsbmb.2021.105952
Li Z, Trakooljul N, Hadlich F, Ponsuksili S, Wimmers K, Murani E. Transcriptome analysis of porcine PBMCs reveals lipopolysaccharide-induced immunomodulatory responses and crosstalk of immune and glucocorticoid receptor signaling. Virulence. 2021;12(1):1808-24. https://doi.org/10.1080/215055 94.2021.1948276 PMid:34288827 DOI: https://doi.org/10.1080/21505594.2021.1948276
Ramos-Casals M, Brahmer JR, Callahan MK, Flores- Chávez A, Keegan N, Khamashta MA, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers. 2020;6(1):38. https://doi.org/10.1038/s41572-020-0160-6 PMid:32382051 DOI: https://doi.org/10.1038/s41572-020-0160-6
Strehl C, Ehlers L, Gaber T, Buttgereit F. Glucocorticoids-all-rounders tackling the versatile players of the immune system. Front Immunol. 2019;10:1744. https://doi.org/10.3389/fimmu.2019.01744 PMid:31396235 DOI: https://doi.org/10.3389/fimmu.2019.01744
Xia C, Liu C, Liu Y, Long Y, Xu L, Liu C. Increased circulating Th1 and Tfh1 cell numbers are associated with disease activity in glucocorticoid-treated patients with IgG4-related disease. J Immunol Res. 2020;2020:3757015. https://doi.org/10.1155/2020/3757015 PMid:33313326 DOI: https://doi.org/10.1155/2020/3757015
Luchak A, Solomon LA, Kanagalingam T, Vijeyakumaran M, Rowe BH, Cameron L. Comparative efficacy of glucocorticoid receptor agonists on Th2 cell function and attenuation by progesterone. BMC Immunol. 2020;21(1):54. https://doi.org/10.1186/s12865-020-00383-8 PMid:33076829 DOI: https://doi.org/10.1186/s12865-020-00383-8
de Castro Kroner J, Knoke K, Kofler DM, Steiger J, Fabri M. Glucocorticoids promote intrinsic human TH17 differentiation. J Allergy Clin Immunol. 2018;142(5):1669-73.e11. https://doi.org/10.1016/j.jaci.2018.07.019 PMid:30092286 DOI: https://doi.org/10.1016/j.jaci.2018.07.019
Oja AE, Brasser G, Slot E, van Lier RA, Pascutti MF, Nolte MA. GITR shapes humoral immunity by controlling the balance between follicular T helper cells and regulatory T follicular cells. Immunol Lett. 2020;222:73-79. https://doi.org/10.1016/j.imlet.2020.03.008 DOI: https://doi.org/10.1016/j.imlet.2020.03.008
Rocamora-Reverte L, Tuzlak S, von Raffay L, Tisch M, Fiegl H, Drach M, et al. Glucocorticoid receptor-deficient Foxp3+ regulatory T cells fail to control experimental inflammatory bowel disease. Front Immunol. 2019;10:472. https://doi.org/10.3389/fimmu.2019.00472 PMid:30936873 DOI: https://doi.org/10.3389/fimmu.2019.00472
Kim D, Nguyen QT, Lee J, Lee SH, Janocha A, Kim S, et al. Anti-inflammatory roles of glucocorticoids are mediated by Foxp3+ regulatory T cells via a miR-342-dependent mechanism. Immunity. 2020;53(3):581-96.e5. https://doi.org/10.1016/j.immuni.2020.07.002 PMid:32707034 DOI: https://doi.org/10.1016/j.immuni.2020.07.002
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Copyright (c) 2021 Alina Petruk, Iryna Kamyshna, Mariia Shkilna, Aleksandr Kamyshnyi (Author)
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