Interleukin-17 is a potential player and treatment target in severe chronic spontaneous urticaria.
Adult
Antibodies, Monoclonal, Humanized
/ administration & dosage
CD4-Positive T-Lymphocytes
/ immunology
Chronic Urticaria
/ drug therapy
Female
Histamine H1 Antagonists
/ administration & dosage
Humans
Interleukin-17
/ immunology
Male
Middle Aged
Omalizumab
/ administration & dosage
Severity of Illness Index
IL-17
autoimmunity
chronic spontaneous urticaria
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
04
02
2020
revised:
12
04
2020
accepted:
25
04
2020
pubmed:
16
5
2020
medline:
13
8
2021
entrez:
16
5
2020
Statut:
ppublish
Résumé
Chronic spontaneous urticaria (CSU) is considered an autoimmune disorder in 50% of cases at least, in which T- and mast cell mediators are considered to be the primary cause of symptoms. However, H This preliminary report examines the possibility that interleukin-17 (IL-17), a cytokine involved in the pathogenesis of many autoimmune diseases, may contribute to CSU and its inhibition may offer a relevant therapeutic target. The expression of IL-17A in skin biopsies of 20 CSU patients and 10 healthy controls was determined by quantitative histomorphometry. We also assessed the response to secukinumab (anti-IL-17A) treatment patients of eight severe CSU (7-day urticaria activity score UAS7 32-40) who were H Increased numbers of CD4+ T cells and mast cells were present in both lesional and non-lesional skin of CSU patients compared with healthy controls. Both types of cells were strongly positive for IL-17A and found to be in close proximity to each other. All eight patients treated with the anti-IL-17A antibody, secukinumab, showed significant improvement in CSU disease activity. The action of secukinumab was shown to be relatively slow in onset. The significant reduction in disease activity from baseline UAS7 was demonstrated to be 55% and 82% at 30 and 90 days, respectively. These findings suggest that IL-17 is involved in the pathogenesis of CSU and that IL-17 should be investigated as a therapeutic target in future studies with larger numbers of patients.
Sections du résumé
BACKGROUND
Chronic spontaneous urticaria (CSU) is considered an autoimmune disorder in 50% of cases at least, in which T- and mast cell mediators are considered to be the primary cause of symptoms. However, H
OBJECTIVE
This preliminary report examines the possibility that interleukin-17 (IL-17), a cytokine involved in the pathogenesis of many autoimmune diseases, may contribute to CSU and its inhibition may offer a relevant therapeutic target.
METHODS
The expression of IL-17A in skin biopsies of 20 CSU patients and 10 healthy controls was determined by quantitative histomorphometry. We also assessed the response to secukinumab (anti-IL-17A) treatment patients of eight severe CSU (7-day urticaria activity score UAS7 32-40) who were H
RESULTS
Increased numbers of CD4+ T cells and mast cells were present in both lesional and non-lesional skin of CSU patients compared with healthy controls. Both types of cells were strongly positive for IL-17A and found to be in close proximity to each other. All eight patients treated with the anti-IL-17A antibody, secukinumab, showed significant improvement in CSU disease activity. The action of secukinumab was shown to be relatively slow in onset. The significant reduction in disease activity from baseline UAS7 was demonstrated to be 55% and 82% at 30 and 90 days, respectively.
CONCLUSIONS
These findings suggest that IL-17 is involved in the pathogenesis of CSU and that IL-17 should be investigated as a therapeutic target in future studies with larger numbers of patients.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Histamine H1 Antagonists
0
IL17A protein, human
0
Interleukin-17
0
Omalizumab
2P471X1Z11
secukinumab
DLG4EML025
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
799-804Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
Kolkhir P, Church MK, Weller K, Metz M, Schmetzer O, Maurer M. Autoimmune chronic spontaneous urticaria: What we know and what we do not know. J Allergy Clin Immunol. 2017;139(6):1772-1781. e1771.
Metz M, Ohanyan T, Church MK, Maurer M. Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: a retrospective clinical analysis. J Dermatol Sci. 2014;73(1):57-62.
Maurer M, Gimenez-Arnau AM, Sussman G, et al. Ligelizumab for chronic spontaneous Urticaria. N Engl J Med. 2019;381(14):1321-1332.
Kay AB, Clark P, Maurer M, Ying S. Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous ('idiopathic') urticaria. Br J Dermatol. 2015;172(5):1294-1302.
Toubi E, Blant A, Kessel A, Golan TD. Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. Allergy. 1997;52(3):312-316.
Lee JK, Simpson RS. Dupilumab as a novel therapy for difficult to treat chronic spontaneous urticaria. J Allergy Clin Immunol Pract. 2019;7(5):1659-1661 e1651.
McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity. 2019;50(4):892-906.
Atwa MA, Emara AS, Youssef N, Bayoumy NM. Serum concentration of IL-17, IL-23 and TNF-alpha among patients with chronic spontaneous urticaria: association with disease activity and autologous serum skin test. J Eur Acad Dermatol Venereol. 2014;28(4):469-474.
Lin W, Zhou Q, Liu C, Ying M, Xu S. Increased plasma IL-17, IL-31, and IL-33 levels in chronic spontaneous urticaria. Sci Rep. 2017;7(1):17797.
Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol. 2018;55(3):379-390.
Noordenbos T, Blijdorp I, Chen S, et al. Human mast cells capture, store, and release bioactive, exogenous IL-17A. J Leukoc Biol. 2016;100(3):453-462.
McInnes IB, Nash P, Ritchlin C, et al. Secukinumab for psoriatic arthritis: comparative effectiveness versus licensed biologics/apremilast: a network meta-analysis. J Comp Eff Res. 2018;7(11):1107-1123.
Patel DD, Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis. 2013;72(suppl 2):iii116-iii123.
Maurer M, Metz M, Bindslev-Jensen C, et al. Definition, aims, and implementation of GA(2) LEN Urticaria Centers of Reference and Excellence. Allergy. 2016;71(8):1210-1218.
Shefler I, Salamon P, Reshef T, Mor A, Mekori YA. T cell-induced mast cell activation: a role for microparticles released from activated T cells. J Immunol. 2010;185:4206-4212.
Cho KA, Park M, Kim YH, Woo SY. Th17 cell-mediated immune responses promote mast cell proliferation by triggering stem cell factor in keratinocytes. Biochem Biophys Res Commun. 2017;487(4):856-861.
Cho KA, Suh JW, Lee KH, Kang JL, Woo SY. IL-17 and IL-22 enhance skin inflammation by stimulating the secretion of IL-1beta by keratinocytes via the ROS-NLRP3-caspase-1 pathway. Int Immunol. 2012;24(3):147-158.