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[Role of IL-17A and neutrophilic granulocytes in the pathogenesis of psoriasis]. Smolyannikova V A,Karamova A E,Nefedova M A Arkhiv patologii OBJECTIVE:To study the expression of IL-17A in the inflammatory infiltrating cells in the plaques as one of the key points in the pathological process in moderate to severe psoriasis. MATERIAL AND METHODS:The material obtained from 50 patients with moderate and severe psoriasis was examined by an indirect immunofluorescence assay to determine the composition of cell infiltrate and the type of IL-17A-producing cells in the foci of lesion. The markers of lymphocytes (CD3), dendritic cells (CD11c), neutrophilic granulocytes (Mpo), and mast cells (Trp) were used. The proliferative activity of basal keratinocytes (Ki-67), the expression of IL-17A, and the co-expression of IL-17A, Mpo, and Trp were also studied. RESULTS:A positive correlation was established between the count of neutrophilic granulocytes in the infiltrate, the expression of IL-17A, and the number of neutrophils expressing IL-17A with the duration of the disease and the severity of the patient's condition. CONCLUSION:Neutrophilic granulocytes and their expression of IL-17A play one of the key roles in the pathogenesis of psoriasis. 10.17116/patol20208201130
Bedside to bench: defining the immunopathogenesis of psoriatic arthritis. Nature reviews. Rheumatology Psoriatic arthritis (PsA) is an immune-mediated, systemic inflammatory disorder. PsA can present with heterogeneous clinical features. Advances in understanding the immunopathogenesis of PsA have helped to facilitate the development of agents targeting specific components of the dysregulated inflammatory and immune responses relevant to PsA. Interestingly, agents with distinct mechanisms of action have shown differential responses across the various disease domains of PsA, counter to what might have been expected from basic science investigations. Here, we review data utilizing various novel targeted therapies for PsA, focusing on biologic and targeted synthetic therapies. These data might support the idea of a 'bedside to bench' concept, whereby results from clinical trials of specific targeted therapies inform our understanding of the immunopathogenesis of PsA. For example, TNF inhibition confers substantial and comparable benefit for all domains of PsA, supporting the view that TNF is a central pro-inflammatory cytokine across diverse areas of disease involvement. On the other hand, inhibition of IL-12-IL-23, as compared with inhibition of TNF, has greater efficacy for psoriasis, comparable efficacy for peripheral arthritis, but was ineffective in studies of axial spondyloarthritis. Data from studies of agents with distinct mechanisms of action will help to further refine our understanding of the immunopathogenesis of PsA. 10.1038/s41584-019-0285-8
The pathogenesis of psoriatic arthritis. Veale Douglas J,Fearon Ursula Lancet (London, England) Psoriatic arthritis is a chronic, immune-mediated, inflammatory arthropathy that presents with inflammation of the joints and entheses, including those of the axial skeleton, and is associated with increased mortality from cardiovascular disease. Diagnosis is primarily based on clinical phenotype because of the diversity of the associated features, which can include skin and nail disease, dactylitis, uveitis, and osteitis. Improved understanding of the pathogenesis of psoriatic arthritis has led to the development of effective biologics and small-molecular drugs targeting specific cytokines and signalling pathways, which can prevent disease progression and improve quality of life. However, at least 40% of patients with psoriatic arthritis have only a partial response or fail to respond to such treatments. Cytokine inhibitors, mainly those specific for tumour necrosis factor and, more recently, the interleukin 23-T-helper-17 cell pathway, have been highly successful in the treatment of disease manifestations in several different tissues, although targeting the interleukin 23-T-helper-17 cell pathway might be more effective in psoriasis than in arthritis. However, the precise mechanisms underlying the pathogenesis of psoriatic arthritis-which include genetics, environmental factors, and immune-mediated inflammation-are complex, and the relationship between disease of the joint and that of other domains is poorly understood. Improving our understanding of psoriatic arthritis pathogenesis could help to establish validated biomarkers for diagnosis, predict therapeutic response and remission, develop precision medicines, and predict which patients will respond to which therapy. We discuss advances in pathogenetic translational research that could inform these issues. 10.1016/S0140-6736(18)30830-4