On May 17-18, 2022, the ACR and the FDA co-sponsored a public meeting to address topics of mutual interest and importance in assessing long-term safety and clinical efficacy, as well as novel approaches to clinical trials in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). During the two-day consensus-building summit, rheumatologists, other health care professionals, and FDA staff provided a broad perspective on current clinical development challenges and potential approaches to address them. Key takeaways are summarized in this document, including issues related to innovative clinical ..read more

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs). These antibodies can bind to DNA, RNA and protein complexes with nucleic acids. Among ANAs, antibodies to DNA (anti-DNA) are markers for classification and disease activity, waxing and waning in many patients. In the blood, anti-DNA antibodies can bind DNA to form immune complexes with two distinct roles in pathogenes ..read more

Objectives Eph/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc). Methods We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting Ephb2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models of skin fibrosis. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward sign ..read more

Abstracts Objectives Glucocorticoid-induced Tumor-Necrosis-Factor-Receptor Family-related Protein (GITR), with its ligand (GITRL), plays an important role in CD4+T-cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren's Syndrome (pSS). Methods pSS patients and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determinated. RNA-Sequencing was performed to decipher key signal pathways. Non Obese Diabetes (NOD) mice was adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transdu ..read more

Arthritis &Rheumatology, EarlyView ..read more

Objective Subsets of CD21–/low memory B cells (MBCs), including double-negative (DN, CD27–IgD–) and Tbet+CD11c+ cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21–/low MBCs correlate with joint destruction. However, whether this is due to the Tbet+CD11c+ subset, its function and pathogenic contribution to RA are unknown. This study aims to investigate the association between CD21–/low Tbet+CD11c+ MBCs and joint destruction as well as other clinical parameters and to elucidate their functional properties in untreated RA patients (uRA). Methods Clinical obs ..read more

Objective Fibroblast-like synoviocytes (FLS) contribute to the pathogenesis of rheumatoid arthritis (RA), in part due to activation of the pro-inflammatory transcription factor NF-κB. Neddylation is modulated by the negative regulator of ubiquitin-like proteins-1 (NUB1). We determined whether NUB1 and neddylation are aberrant in RA FLS thereby contributing to their aggressive phenotype. Methods RA or osteoarthritis (OA) FLS were obtained from arthroplasty synovia. RT-qPCR and Western blot analysis assessed gene and protein expression, respectively. NUB1 was overexpressed using an expression v ..read more

Objective To determine the event-free survival of Australian patients with diffuse systemic sclerosis (dcSSc), who meet eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomised controlled trials (RCTs), but were managed without ASCT. Methods Patients who met inclusion criteria for the ASTIS (Autologous Stem Cell Transplantation International Scleroderma)(1) and SCOT (Scleroderma: Cyclophosphamide Or Transplantation)(2) trials were identified from the multicentre Australian Scleroderma Cohort Study (ASCS). Event-free survival (survival without cardiac ..read more

Arthritis &Rheumatology, Accepted Article ..read more

Arthritis &Rheumatology, Accepted Article ..read more