BackgroundPemphigus vulgaris (PV) is a kind of IgG-mediated autoimmune blistering disease (AIBD) that is characterized by loss of keratinocyte adhesion in the epithelium of mucous membranes or skin. Recently, pemphigus vulgaris was thought to be associated with classical T helper 2 (TH2)-type cytokines such as interleukin‐4 (IL-4) and interleukin‐17 (IL-17) signaling pathway. A humanized monoclonal IgG4 antibody called dupilumab binds to the alpha subunit of the interleukin‐4 receptor (IL‐4Rα) and inhibits the signaling of IL-4 and interleukin‐13 (IL-13), which has been successfully applied for atopic dermatitis and asthma. Currently, the clinical trial evaluating dupilumab in bullous pemphigoid is ongoing.ObjectiveTo determine whether dupilumab may be of benefit in the aggressive refractory pemphigus vulgaris.MethodsWe report a 35-year old male with refractory pemphigus vulgaris and pulmonary tuberculosis who received treatment with dupilumab for 10 weeks. The mRNA expression of peripheral blood mononuclear cells (PBMCs) was analyzed by RNA sequencing (RNA-seq) which showed the gene expression changes after treatment.ResultsThe skin lesions of the patient improved in response to the combined use of dupilumab, moderate dose of glucocorticosteroids, and intravenous immune globulin (IVIG). Downregulations of inflammatory response-related genes and IL-17 signaling pathway-related genes were observed in PBMCs.ConclusionWe describe a patient with refractory pemphigus vulgaris and pulmonary tuberculosis who had the disease under control with combined use of dupilumab as an add-on treatment. Dupilumab may provide a beneficial effect in aggressive refractory pemphigus vulgaris.

Hepatocellular carcinoma (HCC) is still one of the major malignant tumours with poor prognosis. The chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster, and its functions and regulatory mechanisms remain unclear in HCC. We extracted data from 373 HCC samples and 50 non-tumour samples from The Cancer Genome Atlas database. The differential expression levels and methylation levels of C19MC as well as the correlation between them were analysed. We evaluated the correlation between the expression levels of C19MC and the clinical features. We further performed prognostic analysis for C19MC and analysed the bioinformatic function. C19MC had upregulated expression levels and promoter hypomethylation in HCC. A significant negative correlation between the high expression and low methylation level of C19MC was obtained. In addition, the positive correlation between the expression levels of C19MC and the tumour grade, tumour stage and T-stage is shown. Three miRNAs (mir-512-1, mir-516a-1, mir-519a-2) were negatively associated with overall survival on the basis of the Kaplan-Meier analysis and the 3-miRNA signature was significant for the prognostic assessment of HCC.

Although the therapeutic methods of hepatocellular carcinoma (HCC) have made great advances, the current situation is that HCC is the common malignancy. Our previous bioinformatic study presented that two members of C19MC (mir-512-1 and mir-519a-2) acted as crucial roles in the HCC progression. In this study, we first demonstrated that the miR-512-3p and miR-519a-2-5p, which were spliced from the mir-512-1 and mir-519a-2, were the functional mature miRNAs. Meanwhile, both miR-512-3p and miR-519a-2-5p were significantly upregulated in human HCC samples and HCC cell lines. The miR-512-3p and miR-519a-2-5p promoted the proliferation, invasion, and metastasis in vitro and in vivo. Moreover, the two miRNAs co-targeted the downstream tumor suppressors MAP3K2 and MAP2K4 and subsequently achieved the HCC progression. In the clinical cohort, high expression of miR-512-3p and miR-519a-2-5p acted as two risk factors for HCC recurrence and distinguished patients with poor tumor-free survival after radical resection. The integration of the two miRNAs into the AJCC staging system significantly improved the accuracy for the prediction of HCC recurrence. Our study suggests that miR-512-3p and miR-519a-2-5p have similar effects on the promotion of HCC progression. They can be robust markers for the prediction of HCC recurrence and therapy targets.

No abstract