ObjectivePrimary biliary cholangitis (PBC) is an autoimmune disease with significant gender difference. X chromosome inactivation (XCI) plays important roles in susceptibility to diseases between genders. This work focuses on the differences of LncRNA XIST in several defined immune cells populations as well as its effects on naive CD4+ T cells proliferation and differentiation in patients with PBC.MethodsNKs, B cells, CD4+ T, and CD8+ T cells were separated by MicroBeads from peripheral blood mononuclear cells (PBMCs) of PBC patients and healthy control (HC). The expression levels of LncRNA XIST in these immune cells were quantified by qRT-PCR and their subcellular localized analyzed by FISH. Lentivirus were used to interfere the expression of LncRNA XIST, and CCK8 was used to detect the proliferation of naive CD4+ T cells in PBC patients. Finally, naive CD4+ T cells were co-cultured with the bile duct epithelial cells (BECs), and the effects of LncRNA XIST on the typing of naive CD4+ T cells and related cytokines were determined by qRT-PCR and ELISA.ResultsThe expression levels of LncRNA XIST in NKs and CD4+ T cells in PBC patients were significantly higher than those in HC, and were primarily located at the nucleus. LncRNA XIST could promote the proliferation of naive CD4+ T cells. When naive CD4+ T cells were co-cultured with BECs, the expressions of IFN-γ, IL-17, T-bet and RORγt in naive CD4+ T cells were decreased.ConclusionLncRNA XIST was associated with lymphocyte abnormalities in patients with PBC. The high expression of LncRNA XIST could stimulate proliferation and differentiation of naive CD4+ T cells, which might account for the high occurrence of PBC in female.

Background Wilson’s disease (WD) is a rare autosomal recessive disease associated with defective biliary excretion of copper. The simultaneous occurrence of WD and systemic lupus erythematosus (SLE) has seldom been reported. Therefore, this study aimed to report the co-occurrence of SLE and WD with hepatic involvement in a patient so as to improve the understanding of the coexistence of these two conditions. Case presentation A 35-year-old woman with SLE was found to have liver fibrosis during a routinely abdominal ultrasound examination. Her laboratory evaluation showed low serum ceruloplasmin and high 24 h urine copper levels. The slit-lamp examination revealed the presence of Kayseri–Fleischer ring in her cornea. Liver biopsy demonstrated the enlargement of the portal area with hyperplasia of the fibrous tissue, infiltration of lymphoid plasma cells, swelling of hepatocytes, and steatosis, demonstrating liver fibrosis. Ensuing genetic testing confirmed the diagnosis of WD. Conclusions Clinicians should bear in mind that unexplained liver fibrosis in patients with SLE may be related to WD, so as to avoid a missed or delayed diagnosis.

Background and Objective: The aim of this study is to investigate the role of NK cells and their phenotypes in xenobiotic induced murine model of primary biliary cholangitis （PBC）by eliminating NK cells. Methods: C57BL/6 female mice were immunized with 2OA-BSA and poly I:C to develop the murine model of PBC. Serologic, histologic, and immunologic testing of PBC mice were analyzed by depleting NK cells with ASGM1 before (ASGM1+PBC group) or after immunization (PBC+ASGM1 group). The proportions of NK cells, CD62L+NK cells, CD4+, and CD8+T in liver were analyzed. Results: ALT, AST and ALP in PBC mice was increased. In contrast to PBC mice, AST in ASGM1+PBC group was decreased. Moreover, TBIL was decreased in PBC+ASGM1 group. Notably, ALP and titer of AMA in mice treated with ASGM1 was decreased when compared with PBC mice. Comparing with HC, ASGM1+PBC or PBC+ASGM1 group mice, the ratio of CD4+T cells in liver declined in PBC mice. In comparison to HC and ASGM1+PBC group mice, the ratio of CD4+/CD8+T cells in PBC mice was lower. The frequency of CD62L+NK cells in the liver of PBC mice increased. However, there was no significant difference in histological scores among ASGM1+PBC, PBC+ASGM1 and PBC mice. Conclusions: Eliminating NK cells could reduce the degree of cholestasis and improve the immune imbalance. NK cells were functionally involved in pathogenesis and disease progression, especially CD62L+NK cells in liver might aggravate the progression of PBC.

Distal extremity swelling with pitting edema in psoriatic arthritis (PsA) is a rare rheumatological condition, whose management presents a challenge. The aim of the present study was to identify the clinical characteristics of, and formulate a standardized management strategy for, patients with distal extremity swelling with pitting edema in PsA. The medical records of consecutive patients with PsA, with or without distal extremity swelling with pitting edema, were systematically analyzed over a ~10-year period (between September 2008 and September 2018) in a single center and a comprehensive review (pathogenic mechanisms, clinical manifestations, and treatments) was undertaken. A total of 167 patients with PsA were evaluated, and distal extremity swelling with pitting edema was recorded in 16 of these patients. In three of the 16 patients, distal extremity swelling with pitting edema occurred as the first, isolated manifestation of PsA. The upper and lower extremities were affected, predominantly asymmetrically. Female patients with PsA were more likely to be affected with pitting edema and the blood test results revealed that the patients with PsA and pitting edema also presented with a significantly higher erythrocyte sedimentation rate and concentration of C-reactive protein. The onset of pitting edema was associated with the activity of the disease. Lymphoscintigraphy and magnetic resonance imaging (MRI) scans revealed that edema might have resulted from inflammation of the tenosynovial structures. Furthermore, treatment with tumor necrosis factor-α inhibitor (TNFi) elicited improvements in patients with pitting edema that were not responsive to conventional synthetic disease-modifying antirheumatic drug therapy. In conclusion, distal extremity swelling with pitting edema, also termed atypical remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, may represent the initial isolated manifestation of PsA. The atypical RS3PE syndrome in PsA was attributable to inflammation of the tenosynovial structures, and TNFi may serve as a potential treatment.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune systemic disease with a wide range of clinical symptoms, complex development processes, and uncertain prognosis. The clinical treatment of SLE is mainly based on hormones and immunosuppressants. Research on novel therapy strategies for SLE has flourished in recent years, especially the emergence of new targeted drugs and natural products that can modulate related symptoms. This review discusses the current experience including B-cell targeted drugs (belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab), T-cell targeted drugs (abatacept, dapirolizumab, and inhibitor of syk and CaMKIV), cytokines targeted drugs (anifrolumab and sifalimumab), and natural products (curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol). The aim of this paper is to combine the existing in vitro and in vivo models and clinical research results to summarize the efficacy and mechanism of natural drugs and targeted drugs in SLE for the reference and consideration of researchers.