RESUMO
Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.
Assuntos
Produtos Biológicos , Interleucina-17 , Psoríase , Receptores de Interleucina-17 , Humanos , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Interleucina-17/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Psoríase/tratamento farmacológico , Psoríase/genética , Qualidade de Vida , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Receptores de Interleucina-17/genéticaRESUMO
Psoriasis vulgaris, a chronic inflammatory skin disorder, is the result of immune mediated processes, genetic background and environmental factors. Prolactin and the vascular endothelial growth factor seem to play a key role in psoriasis pathogenesis regarding hyperproliferation of epidermal keratinocytes and dermal vascular ectasia. The aim of the study was to investigate the expression of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor receptor 2 (VEGFR2) and prolactin receptor (PRLR) in psoriatic skin by immunohistochemical analysis and to evaluate the correlation with disease severity. Two skin biopsies, psoriatic lesion and perilesional skin, obtained by punch biopsy from 19 nontreated psoriasis patients were examined in hematoxylin and eosin staining and immunohistochemistry (IHC) for TNF-α, VEGFR2 and PRLR. The indirect IHC reaction was carried out automatically and visualized by 3,3-diaminobenzidine (DAB) technique. The average number of DAB-positive cells and the intensity of cell staining were quantified on a predefined scale. The results show a significant difference in the quantity and distribution of TNF-α positive cells in the two sample groups. In psoriatic plaque skin, an increased expression of TNF-α was found in the perivascular dermis and epidermic keratinocytes. In perilesional skin the immunostaining was predominant in the basal layer keratinocytes, while in psoriatic plaque, all the layers were positively marked, with stronger expression at the base. A statistically significant difference was found between the intensity of the immunostaining in the two types of tissue. Positive cells for VEGFR2 and PRL were identified in the basal layer keratinocyte cells (VEGFR2), sweat glands and hair outer shaft sheath (PRLR), without significant differences between the two types of samples. Our findings confirm the importance of TNF-α in psoriasis pathogenesis and a positive correlation with lesions severity. No significant differences were found for VEGFR2 and PRLR, but additional studies are necessary to establish their role.