Investigating expression pattern of eight immune-related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy
DERMATOLOGIC THERAPY
Authors: Tavakolpour, Soheil; Mahmoudi, Hamidreza; Karami, Fatemeh; Behjati, Somayeh Elikaei; Balighi, Kamran; Abbasi, Maryam; Farid, Ali Salehi; Masoudi, Jamileh; Balali, Mansour; Daneshpazhooh, Maryam; Modarressi, Mohammad Hossein
Abstract
Pemphigus is a rare group of autoimmune diseases, which its exact molecular pathogenesis and therapeutic biomarkers remained unknown. In this regard the expressions of eight immune-related genes was evalualted in pemphigus patients. Forty-six pemphigus patients, either new case or on minimal therapy, were recruited. The expressions of IL22, IL9, IL21, EBI3, TNFSF13B, FCGR3A, CTLA4, and PDCD1 genes were analyzed at baseline, compared with 32 healthy controls, and their changes were monitored 3 months after rituximab (RTX) therapy through Reverse Transcriptase Real-time PCR (RT-Real-time PCR). Except of IL21, which was similar in both groups, expressions of other genes were significantly lower in patients compared with the controls (P-value <.05). PDCD1, EBI3, IL21, and IL22 genes were significantly overexpressed three months following RTX administration (P-value <.05). Higher prednisolone dosage and PDAI-score were positively correlated with CTLA4 and FCGR3A expressions after 3 months, respectively (P-value = .019 and .048, respectively). Anti-desmoglein 1 (Dsg 1) titer and its positivity at baseline were associated with TNFSF13B expression, FCGR3A expressions, and the PDAI-score. Our results suggest the possible involvement of some gene expressions in pemphigus immunopathogenesis, which could be affected by RTX therapy and also might be used as prognostic biomarkers.
MicroRNA let-7a Ameliorates Con A-Induced Hepatitis by Inhibiting IL-6-Dependent Th17 Cell Differentiation
JOURNAL OF CLINICAL IMMUNOLOGY
Authors: Zhang, Yingying; Wang, Xiangmin; Zhong, Min; Zhang, Mengying; Suo, Qifeng; Lv, Kun
Abstract
In this study we explored the effects of microRNA let-7a on Con A-induced hepatitis and its possible mechanisms involved. We demonstrated that IL-6 and IL-17 expression were significantly upregulated in the liver following Con A treatment and IL-6 level was correlated with the IL-17 expression. To explore whether let-7a may have therapeutic effect on Con A-induced hepatitis, mice was infected with a lentiviral vector containing the let-7a sequence 7 days before Con A treatment. Significantly reduced Th17 cells and remarkably increased regulatory T cells frequency in the liver tissue were found as compared to control mice. It was accompanied by a significant decreased level of inflammatory cytokines as TNF-alpha, IL-6 and IFN-gamma in the serum, and an decreased level of Th17 lineage-specific genes such as Il17a, Il17f, Il21 and Il23r. let-7a was further found to inhibit Th17 differentiation by downregulating IL-6 secretion. It may represent as a novel therapeutic strategy in treating immune-mediated inflammatory hepatitis.