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Background: Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy., Objectives: To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort., Methods: A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single-nucleotide polymorphisms in 14 susceptibility genes, and HLA-Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients., Results: Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX., Conclusions: Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX., (© 2019 British Association of Dermatologists.)

Background: Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified., Objectives: To analyse serum total IgE levels in addition to the presence and distribution of IgE and FcεRI in psoriatic lesions, and to investigate alteration of IgE and FcεRI after successful systemic treatment., Methods: Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and FcεRI was investigated using immunohistochemistry and double immunofluorescence., Results: Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and FcεRI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and FcεRI+ cells decreased significantly after successful therapy with ustekinumab. IgE and FcεRI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils., Conclusions: IgE might participate in the development of psoriasis by activating FcεRI-bearing cells., (© 2016 British Association of Dermatologists.)

Background: Psoriasis is a chronic, relapsing, inflammatory skin disease, in which regulatory T cells (Tregs) play an important role. Recently, human Treg ectoenzymes (CD39/CD73) have been reported to mediate the suppressive activity of Tregs., Aim: To investigate the proportions of CD39/CD73 expressing Foxp3(+) regulatory T cells in different types of psoriatic lesions., Methods: Immunohistochemical staining was used to analyse expression of Foxp3, CD39 and CD73 in biopsy tissue from healthy controls and from patients with different types of psoriasis., Results: In normal control biopsies, CD39(+) cells were scattered throughout the epidermis and dermis, while CD73(+) cells were localized predominantly in the dermis. The proportion of cells that were both CD39(+) and Foxp3(+) was significantly lower in pustular psoriasis (PP) and erythrodermic psoriasis (EP) than in psoriasis vulgaris (PV) (25.0 ± 2.6%, 26.5 ± 2.0% and 45.1 ± 3.5%, respectively; P < 0.001). Likewise, CD73(+) Foxp3(+) cells were lower in PP and EP than in PV (6.2 ± 1.9%, 11.6 ± 2.8% and 17.7 ± 2.3% respectively, P < 0.001). There were no significant differences in the population size of double-staining cells in EP compared with PP., Conclusion: The relative reduced expressions of CD39 and CD73 within Foxp3(+) Tregs may imply a different immunopathogenesis for different psoriatic lesions., (© 2014 British Association of Dermatologists.)

Background: Differences in the number of Foxp3+ regulatory T cells (Tregs) in lesional skin and peripheral blood and their functioning in plaque vs. guttate psoriasis have not been reported., Objectives: To investigate whether there is a differential expression of Foxp3+ Tregs and a differential regulation of inflammatory cytokines in plaque vs. guttate psoriasis vulgaris., Methods: The number and the percentage of Foxp3+ cells in different phases of skin lesions of patients with plaque and guttate psoriasis vulgaris were assessed by immunohistochemical staining. The expression of Foxp3 and interleukin (IL)-17 protein in CD4 populations was measured by flow cytometry. Inflammatory cytokine production by transforming growth factor-beta1-induced Foxp3+ Tregs was assessed in an in vitro study. The cytokines in supernatant and serum were determined by enzyme-linked immunosorbent assay., Results: The percentage of Foxp3+ CD3+ cells in the papillary layer was higher than in the reticular layer of dermis and in epidermis (P < 0.05). The numbers of Foxp3+ Tregs in skin lesions and peripheral blood were higher in plaque than in guttate psoriasis, whereas the percentage of IL-17+ CD4+ cells was higher in guttate than in plaque psoriasis (P < 0.05). The numbers of Foxp3+ cells were positively correlated with the Psoriasis Severity Index score of skin lesions (P < 0.0001), and the percentages of Foxp3+ CD4+ cells in peripheral blood were positively correlated with the Psoriasis Area and Severity Index score of patients (P < 0.05). The inhibitory functions of Tregs to IL-17 and IL-6 in guttate psoriasis and to tumour necrosis factor-alpha in plaque psoriasis were deficient., Conclusions: Differential expression and regulatory functioning for inflammatory cytokine production by Foxp3+ Tregs may imply a different immunopathogenesis for plaque and guttate psoriasis.