ObjectivesOpen-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy.MethodsA randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets.ResultsAt week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells.ConclusionsLow-dose IL-2 might be effective and tolerated in treatment of SLE.Trial registration numberClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

Aims: Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue. Materials and methods:The AGREE II instrument and the ADAPTE Collaboration framework were applied to systematically identify, appraise, synthesize, and adapt international rheumatoid arthritis guidelines for use in the Asia-Pacific region.Results: Forty rheumatoid arthritis treatment recommendations, based on evidence and expert opinion, were drafted and are presented in this report. Conclusion: The Asia Pacific of Associations for Rheumatology rheumatoid arthritis treatment recommendations are intended to serve as a reference for best practice management of rheumatoid arthritis in Asia-Pacific, focusing on local issues to ensure the delivery of basic care for these patients, and to improve their outcomes. In addition, the document will serve as a reference for national rheumatology associations in Asia-Pacific for developing guidelines in their respective countries.

The objective of this study was to investigate the manifestations, treatment and outcome of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (SLE) patients. The charts of 185 pediatric patients with SLE diagnosed between 1985 and 2005 in a tertiary referral hospital were retrospectively reviewed. NPSLE were defined using the American College of Rheumatology NPSLE case definitions. NPSLE developed in 34.6% (64/185) of the patients. The mean onset age was 15.2 years. Fourteen patients (21.9%) had NP manifestations on initial diagnosis of SLE. The median duration from the onset of SLE to NP manifestation was 11 months. The most frequent NP manifestations were seizure disorder (84.4%), ischemic stroke (28.1%) and psychosis (21.9%). However, the prevalence of manifestations of NPSLE might be underestimated by the retrospective design of our study. Higher mean C3/C4 levels, less percentage of anti-dsDNA antibodies elevation and higher percentage of elevated anticardiolipin antibodies were observed in NPSLE events than in non-NPSLE events (P < 0.05). The mortality rate of NPSLE patients decreased from 52.2% in 1985-1994 cohort to 27.8% in 1995-2005 cohort. In the past 10 years, the leading cause of death in NPSLE patients was NPSLE itself. NPSLE is common in pediatric SLE patients. It has diverse manifestations and a high mortality.

Over the past decade, it has been debated whether retaining bindings in working memory (WM) requires more attention than retaining constituent features, focusing on domain-general attention and space-based attention. Recently, we proposed that retaining bindings in WM needs more object-based attention than retaining constituent features (Shen, Huang, & Gao, 2015, Journal of Experimental Psychology: Human Perception and Performance, doi: 10.1037/xhp0000018 ). However, only unitized visual bindings were examined; to establish the role of object-based attention in retaining bindings in WM, more emperical evidence is required. We tested 4 new bindings that had been suggested requiring no more attention than the constituent features in the WM maintenance phase: The two constituent features of binding were stored in different WM modules (cross-module binding, Experiment 1), from auditory and visual modalities (cross-modal binding, Experiment 2), or temporally (cross-time binding, Experiments 3) or spatially (cross-space binding, Experiments 4-6) separated. In the critical condition, we added a secondary object feature-report task during the delay interval of the change-detection task, such that the secondary task competed for object-based attention with the to-be-memorized stimuli. If more object-based attention is required for retaining bindings than for retaining constituent features, the secondary task should impair the binding performance to a larger degree relative to the performance of constituent features. Indeed, Experiments 1-6 consistently revealed a significantly larger impairment for bindings than for the constituent features, suggesting that object-based attention plays a pivotal role in retaining bindings in WM.

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13.1 (RPL3/SYNGR1). We also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC.