Interleukin-17 is a potential player and treatment target in severe chronic spontaneous urticaria.

Abstract

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, H1 -antihistamines, cyclosporine A, and omalizumab fail to achieve complete symptom amelioration in up to 70% of patients. This suggests that other inflammatory pathways are involved and that additional and more effective treatments need to be developed.

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 H1 -antihistamine and omalizumab-resistant.

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.

• Authors: D A Sabag, L Matanes, J Bejar, H Sheffer, A Barzilai, M K Church, E Toubi, M Maurer, Z Vadasz
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 50 Issue 7 Pg. 799-804 (07 2020) ISSN: 1365-2222 [Electronic] England
• PMID: 32412136 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal, Humanized
• Histamine H1 Antagonists
• IL17A protein, human
• Interleukin-17
• Omalizumab
• secukinumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Chronic Urticaria (drug therapy, immunology, pathology)
• Female
• Histamine H1 Antagonists (administration & dosage)
• Humans
• Interleukin-17 (immunology)
• Male
• Middle Aged
• Omalizumab (administration & dosage)
• Severity of Illness Index