Annals of the Rheumatic Diseases

ObjectivesTo assess whether baseline ESR-CRP difference (D score) is associated with discontinuation due to loss of efficacy during Janus kinase inhibitor therapy after biologic failure in rheumatoid arthritis. MethodsSingle-centre retrospective cohort of 24 patients with rheumatoid arthritis who initiated a Janus kinase inhibitor after inadequate response to at least one biologic DMARD. D score was ESR (mm/h) minus CRP (mg/L). The primary outcome was discontinuation due to loss of efficacy; ot...

ObjectiveIdentifying risk factors enables stratification of patients susceptibility to inflammatory arthritis immune-related adverse events (IA-irAE). This retrospective study examines whether preexisting osteoarthritis (OA) increases the likelihood of de novo IA in patients treated with immune checkpoint inhibitors (ICIs). MethodsThe prevalence of OA among ICI-treated patients who developed IA-irAE, those who developed other types of irAEs but not IA (non-IA irAE), and those who did not develo...

BackgroundGout is the among the most prevalent arthritides worldwide and is associated with high morbidity, cardiovascular risk, and substantial healthcare burden. Despite effective urate-lowering therapies (ULT), many patients remain undertreated, particularly those with severe or complex disease. Nurse-led gout management has improved outcomes in primary care, but data in multimorbid tertiary center populations are lacking. ObjectiveTo evaluate the effectiveness of a supervised nurse-led gout...

ObjectivesResearch of refractory disease in juvenile idiopathic arthritis (JIA) is limited, and a potential genetic contribution has yet to be investigated. This study aimed to explore the presence of rare monogenic disease gene coding variants in a refractory JIA population. MethodsCases were included with a record of inefficacy for methotrexate and [≥]1 biologic drug or exposure to methotrexate and [≥]2 biologic drugs for any reason. Whole exome sequencing data were analysed using VarSe...

IntroductionPain is often persistent in patients with inflammatory arthritis (IA). There is limited research on pain mechanisms in early IA. We used detailed assessments to characterise pain types longitudinally. MethodsThis prospective observational study investigated the relative contribution of peripheral versus centrally mediated pain in newly diagnosed IA patients with pain scores [≥]3, followed over two years. Assessments included: disease activity (Disease Activity Score-28, musculosk...

ObjectivesMosaic chromosomal alterations (mCAs) increase with age and are associated with many diseases, including autoimmune diseases. The associations between mCAs and systemic sclerosis (SSc) and its clinical subtypes have not been explored. MethodsWe recruited study subjects from two independent datasets (Set 1: 635 SSc, 4,401 controls; Set 2: 347 SSc, 2,170 controls) and detected mCAs (Loss, LOH, Gain, and mLOX) from their peripheral blood samples. Logistic regression analyses were conduct...

Individuals who have serum elevations of anti-cyclic citrullinated protein (anti-CCP) antibodies are at risk for developing rheumatoid arthritis (RA), yet immunologic factors that lead to a transition from pre- to clinical RA remain unclear. Here, we used materials from anti-CCP antibody-positive individuals enrolled in a clinical trial that evaluated the efficacy of hydroxychloroquine to prevent clinical RA, and performed multi-modal single-cell profiling (transcriptome, surface proteins, T/B-c...

ObjectivesTo investigate genetic architecture and identify novel risk loci shared between juvenile idiopathic arthritis (JIA) and other human leukocyte antigen (HLA)-associated autoimmune diseases (AIDs) by leveraging genome-wide association studies (GWAS) data. MethodsWe analyzed GWAS summary statistics from over two million participants (123,997 cases and 1,843,249 controls) of European ancestry across multiple AIDs including JIA, autoimmune thyroid disease (AITD), celiac disease, inflammator...

ObjectiveSystemic lupus erythematosus (SLE) is characterized by persistent type I interferon (IFN) signaling and adaptive immune dysregulation. We previously identified hypomethylation of HLA-DRB1 and STAT1 in SLE CD8+ T cells, enabling aberrant IFN-driven HLA-DRB1 expression and expansion of a distinct CD8+ T cell subset. This study aimed to comprehensively characterize CD8+ HLA-DRB1+ T cells in lupus. MethodsPeripheral blood CD8+ T cells from SLE patients and healthy controls were analyzed by...

Autoimmune inflammatory myopathies (AIM) with prominent B cell aggregates (BCM) on muscle biopsy is an uncommon finding. We aimed to compare the characteristics and clinical course of patients with BCM on muscle biopsy to those without and characterize B cell infiltrates in the muscle of these patients. We performed a retrospective study of subjects with AIM in the Canada Inflammatory Myopathy Study (CIMS) cohort to identify cases with BCM on muscle biopsy, which was defined as [≥]30 CD20+ c...

Systemic autoimmune rheumatic diseases (SARDs) are a heterogeneous group of autoimmune conditions characterized by immune system dysregulation leading to chronic inflammation and tissue damage. The overlapping clinical manifestations make differential diagnosis challenging, highlighting the need for novel biomarkers to facilitate early diagnosis, stratification, and personalized treatment. Five SARDs including idiopathic inflammatory myopathies (n=210), rheumatoid arthritis (n=84), systemic scle...

ObjectivesRheumatoid arthritis (RA) exhibits clinical and biological heterogeneity, with synovial tissue stratified into histological pathotypes: lympho-myeloid, diffuse-myeloid, and pauci-immune fibroid. Although GWAS have uncovered RA risk loci, how genetic risk relates to synovial immunopathology remains unclear. To better understand how genetic predisposition may shape divergent early disease mechanisms, we characterised the expression patterns of GWAS-identified RA susceptibility genes and ...

ObjectivesCardiovascular risk excess in rheumatoid arthritis (RA) cannot be explained by traditional risk factors alone. Recent experimental data have identified ALDH4A1 as a mitochondrial self-antigen implicated in atherosclerosis, yet its clinical significance in human autoimmunity remains unexplored. We aimed to characterize ALDH4A1 and anti-ALDH4A1 antibody levels in early RA, and evaluate their associations with atherosclerosis burden and lipoprotein traits. MethodsALDH4A1 and anti-ALDH4A1...

BackgroundHaploinsufficiency of A20 (HA20) is an immune dysregulation disorder caused by loss-of-function TNFAIP3 mutations. This international multicenter study aimed to delineate its clinical spectrum, genetic basis, and natural history. MethodsA cross-sectional, retrospective analysis was conducted in HA20 patients with pathogenic or likely pathogenic TNFAIP3 variants. Clinical, laboratory and treatment data were assessed. Clustering analysis was applied to evaluate clinical features and dis...

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by metabolic dysregulation, including altered lipid metabolism. While polyunsaturated fatty acids have been studied, the plasma levels, endogenous synthesis, and relevance of monounsaturated fatty acids (MUFAs) in RA remain unclear. This study examined plasma MUFA levels in RA and their associations with disease activity, adiposity, and intake. MethodsIn this cross-sectional study, 59 individuals with rheumatoid...

Predictors of Health-Related Quality of Life in Indonesian Women with Systemic Lupus Erythematosus: A Cross-Sectional Within-Cohort Analysis ObjectiveThis study aims to determine the effects of sleep quality along with age, marital status, socioeconomic status, depression, anxiety, disease activity, pain scale, and dose of corticosteroids on quality of life in women with SLE. MethodsVariables were assessed in 75 women with SLE using the Pittsburgh Sleep Quality Index (PSQI), Lupus Quality of L...

ObjectivesEosinophilic granulomatosis with polyangiitis (EGPA) is classified as a subtype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A recent genome-wide association study (GWAS) of EGPA in populations of European ancestry reported several susceptibility loci. In view of population differences in genetic factors of AAV, we made an attempt to examine the contribution of these loci to EGPA in a Japanese population. MethodsThe EGPA associated variants in LPP, TSLP,...

Autoantibody internalization has been implicated in autoimmune disease pathogenesis, yet its mechanisms, and generality across different diseases, cell types, and affected tissues remain poorly defined. Using bulk RNA sequencing, we identified reproducible, autoantibody-specific transcriptomic signatures consistent with autoantigen dysfunction in muscle biopsies from patients with anti-Mi2 dermatomyositis and anti-PM/Scl scleromyositis across independent cohorts. Electroporation of purified pati...

ObjectiveQuantitative computed tomography (QCT) can automatically quantify parenchymal abnormalities on chest CT imaging using deep learning. We leveraged QCT to detect pulmonary abnormalities in patients with early rheumatoid arthritis (RA) compared to healthy controls. MethodsWe analyzed high-resolution CT chest imaging from participants with early RA in the prospective, multicenter, SAIL-RA study and healthy non-smoking controls from the COPDGene study. A deep learning classifier quantified ...

Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with Systemic Lupus Erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within the IRF7 gene. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition rec...