Objective: High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes.
Methods: Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed.
To evaluate experience in a tertiary rheumatology service with melanoma differentiation-association-protein-5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti-MDA5 positivity was detected in 2% of myositis-specific antibody tests. Of these, 29% did not have features consistent with anti-MDA5 disease.
View Article and Find Full Text PDFObjectives: Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjogren's disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterised.
Methods: Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity.
The first inhabitants of Australia and the traditional owners of Australian lands are the Aboriginal and Torres Strait Islander peoples. Aboriginal and Torres Strait Islander peoples are two to four times more likely to have systemic lupus erythematosus (SLE) than the general Australian population. Phenotypically, SLE appears distinctive in Aboriginal and Torres Strait Islander peoples and its severity is substantially increased, with mortality rates up to six times higher than in the general Australian population with SLE.
View Article and Find Full Text PDFBackground: Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials.
View Article and Find Full Text PDFIntroduction: Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses of the 52-week, randomised, phase 3 TULIP-1 and TULIP-2 trials.
Methods: Patients with moderate to severe SLE were enrolled in TULIP-1 and TULIP-2 and received intravenous anifrolumab or placebo alongside standard therapy.
Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis.
View Article and Find Full Text PDFAntigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing.
View Article and Find Full Text PDFBackground: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review.
Objective: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS.
Methods: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators.
Background: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy.
View Article and Find Full Text PDFAutoimmune rheumatic disease (AIRD) is a collective term, which comprises a group of multisystem inflammatory autoimmune diseases, including connective tissue disease, chronic inflammatory arthritis, sarcoidosis and systemic vasculitis. Some AIRD are prevalent in the general population, and all can cause significant morbidity and reduced quality of life, with some increasing the risk of premature mortality, such as systemic lupus erythematosus (SLE), a connective tissue disease that is more prevalent and severe in Australian Aboriginal and Torres Strait Islander Peoples with high mortality rates. To ensure that management of AIRD can be optimised for all Australians, it is important that we understand the prevalence and potential phenotypic variations of AIRD across the Australian population.
View Article and Find Full Text PDFObjective: Irreversible organ damage is common in patients with systemic lupus erythematosus (SLE). Despite evidence of increased prevalence and severity of SLE in Asia Pacific, organ damage is less well studied in this region. This systematic review aims to identify predictors of organ damage in SLE in the Asia Pacific region.
View Article and Find Full Text PDFObjective: The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity.
Methods: SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria.
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies.
Methods: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array.
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