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To examine genes expressed specifically in labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS) in comparison with those of patients with immunoglobulin (Ig)G4-related disease (IgG4-RD), and to identify the genes involved in the pathogenesis of SS. Gene expression in LSGs of SS patients, IgG4-RD patients and healthy controls (HC) was analysed by cDNA microarray. Quantitative polymerase chain reaction (qPCR) was used to validate the up-regulation of differentially expressed genes (DEGs) in SS. Protein production of the validated gene in LSGs was examined by immunofluorescence (IF) assay. The association of molecular functions of the gene with the pathological conditions in SS was examined using peripheral blood lymphocytes. Among 1320 DEGs up-regulated in SS, qPCR confirmed the up-regulation of NR4A2 in LSGs of SS compared with IgG4-RD. IF staining showed higher production of NR4A2 in nuclei of CD4+ T cells and interleukin (IL)-17-producing cells in LSGs of SS, compared with IgG4-RD. Over-expression of NR4A2 mRNA was observed in peripheral CD4+ T cells of SS patients, compared with HC. Nuclear NR4A2 expression in T helper type 17 (Th17)-polarized CD4+ T cells determined by cellular IF was significantly higher in SS than in HC. Importazole, an inhibitor of importin-β, inhibited nuclear transport of NR4A2 and Th17 polarization along with IL-21 expression in naive CD4+ T cells under Th17-polarizing conditions, but did not alter retinoic acid receptor-related orphan receptor C (RORC) expression. NR4A2 seems to promote Th17 polarization via increased expression and intranuclear localization in CD4+ T cells of SS patients, which could play a critical role in the pathogenesis of SS. [ABSTRACT FROM AUTHOR]

We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3+ T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R-/-) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1-/-) mice (M3R-/-→Rag-1-/-) with MIS. Immunized M3R-/- mice (pretransfer treatment) and M3R-/-→Rag-1-/- mice (post-transfer treatment) were treated with A213 every 3 days. Salivary volume, severity of sialadenitis and cytokine production from M3R peptide-stimulated splenocytes and lymph node cells were examined. Effects of A213 on cytokine production were analysed by enzyme-linked immunosorbent assay (ELISA) and on T helper type 1 (Th1), Th17 and Th2 differentiation from CD4+ T cells by flow cytometry. Pretransfer A213 treatment maintained salivary volume, improved MIS and reduced interferon (IFN)-γ and interleukin (IL)-17 production significantly compared with phosphate-buffered saline (PBS) ( P < 0·05). These suppressive effects involved CD4+ T cells rather than CD11c+ cells. Post-transfer treatment with A213 increased salivary volume ( P < 0·05), suppressed MIS ( P < 0·005) and reduced IFN-γ and IL-17 production ( P < 0·05). In vitro, A213 suppressed IFN-γ and IL-17 production from M3R-stimulated splenocytes and CD4+ T cells of immunized M3R-/- mice ( P < 0·05). In contrast with M3R specific responses, A213 suppressed only IL-17 production from Th17 differentiated CD4+ T cells without any effect on Th1 and Th2 differentiation in vitro. Our findings suggested that RORγt antagonism is potentially suitable treatment strategy for SS-like sialadenitis through suppression of IL-17 and IFN-γ production by M3R-specific T cells. [ABSTRACT FROM AUTHOR]

The article focuses on a study which aims to identify predictors for the response to the treatment of acute lupus hemophagocytic syndrome (ALHS). It states that patients treated with cyclosporine A (CsA), serum ferritn was higher in CsA responders. It mentions that low C-reactive protein (CRP) and high hemoglobin can predict positive response to corticosteroid monotherapy while high serum ferritin and low leukocyute count can predict response to CsA in patients with ALHS.

A letter to the editor is presented regarding the article on the use of magnetic resonance imaging to determine the fascial vasculitis in a patient with microscopic polyangiitis.

The article presents a case study of a man with pansclerotic morphea which was complicated with hypohidrosis accompanied by high levels of serum anti-M3R autoantibodies. The man had medical history of hyperlipidaemia and ulcer. Physical examination revealed diffuse and mildly sclerotic skin which was also bright.