RESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Linfocitos T CD4-Positivos , Urticaria Crónica , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Interleucina-17/inmunología , Omalizumab/administración & dosificación , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/inmunología , Urticaria Crónica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
The presence of T regulatory cells (Tregs) is highly required in normal skin in order to maintain immune tolerance to commensal microbes and to prevent the development of immune-mediated inflammation. Psoriasis is a chronic inflammatory skin disease in which effector T cells, namely, Th17 and their relevant pro-inflammatory cytokines are increased in peripheral blood as well as in the inflamed skin. The status of Tregs in psoriatic skin is continuously studied. In this case, CD4 + CD25high T cells and other regulatory cytokines such as IL-35 are demonstrated to be significantly decreased. Aiming to better characterize Tregs in psoriatic skin and to establish the finding of their abnormal balance, we assessed the expression of semaphorin3A and neuropilin-1 (both reported as biomarkers of Tregs). Semaphorin3A and neuropilin-1 expressing Tregs were found to be significantly decreased in psoriatic skin when compared to normal skin. These findings were supported by demonstrating the downregulation of IL-10 expression in psoriatic skin. Our findings suggest that semaphoring3A may turn to be a new promising therapeutic approach in the process of improving Treg function in psoriasis.