The latest medical research on Rheumatology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about rheumatology gathered by our medical AI research bot.
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Rheumatic diseases in Africa.Nature Reviews Rheumatology
Historically, rheumatic diseases have not received much attention in Africa, particularly in sub-Saharan Africa, possibly owing to a focus on the o...
Transcriptomic evaluation of pediatric localized scleroderma skin with histological and clinical correlation.Arthritis Rheumatol
Juvenile localized scleroderma (jLS) is an autoimmune disease of the skin in which the pathogenesis is not well understood due to its rarity. Our goal was to determine the skin transcriptome of LS tissue compared with healthy controls to identify molecular targets using RNA sequencing (RNAseq). Differentially expressed genes (DEGs) identified in jLS patients were compared with histopathological features, clinical features and used to cluster jLS patients.
RNAseq was performed on paraffin-embedded skin (n=28 jLS, n=10 pediatric healthy) using the Illumina HTS and TrueSeq Access library preparation, aligned with STAR and analyzed using DESeq2. Standardized histology scoring was developed for inflammation and collagen deposition and was completed by 2 blinded pathologists. Spearman's correlation was used to determine significance between DEGs and histology.
We identified 589 significant DEGs between jLS and controls. Hierarchical clustering demonstrated three distinct jLS immunophenotype groupings. Degree of inflammatory cell infiltrates significantly correlated with HLA-DPB1, HLA-DQA2, HLA-DRA, and STAT1 (rs> 0.5, p<0.01). Collagen thickness correlated with collagen organization genes, but also with genes identified in the inflammatory infiltrate correlation, such MHC Class I and II and interferon gamma signaling.
The identified groupings of jLS patients showed three distinct genetic signatures, one with upregulated inflammatory-related pathways, which corresponded to inflammatory infiltrate score, a second group with upregulated fibrosis-related pathways, and a third which corresponded to healthy skin gene expression. HLA Class II gene upregulation was observed within the inflammatory group, which has also been described for morphea peripheral blood and systemic sclerosis skin.
Notch-1 and Notch-3 Mediates Hypoxia-Induced Synovial Fibroblasts Activation in Rheumatoid Arthritis.Arthritis Rheumatol
To fully understand the molecular mechanism of hypoxia-induced rheumatoid arthritis synovial fibroblast cell (RASFC) activation via Notch-1 and Notch-3 signalling, and to evaluate its potential as a therapeutic target.
Notch-1 and Notch-3 intracellular domain (N1ICD), Notch-3 intracellular domain (N3ICD), and hypoxia-inducible factor-1α (HIF-1α) were detected in RA synovial tissues via immunohistology. RASFC were cultured under hypoxic and normoxic conditions with or without small interfering RNAs, and N1ICD and N3ICD were overexpressed under normoxic conditions. Collagen-induced arthritis (CIA) rats were administered with LY411575 (inhibition of N1ICD and N3ICD) for 15 and 28 days, and its therapeutic efficacy was assessed by histology, radilology and inflammatory cytokine detection.
In the study, we found that N1ICD, N3ICD and HIF-1α were abundantly expressed in RA patient synovial tissues. Meanwhile, HIF-1α was found to directly regulate the expression of Notch-1 and Notch-3 genes under hypoxic conditions. Moreover, hypoxia induced N1ICD and N3ICD expression in RASFC was blocked by HIF-1α small interfering RNA (siHIF-1α). Notch-1 small interfering RNA (siNotch-1) and Notch-3 small interfering RNA (siNotch-3) inhibited hypoxia-induced RASFC invasion and angiogenesis in vitro, whereas N1ICD and N3ICD overexpression promoted these processes. In addition, it was revealed that Notch-1 regulates RASFC migration and epithelial-mesenchymal transition (EMT) under hypoxia, whereas Notch-3 regulates anti-apoptosis and autophagy. Further, in vivo studies showed that N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect on CIA rats.
Collectively, this study has identified a functional link between HIF-1α, Notch-1, and Notch-3 signalling in regulating RASFC activation and rheumatoid arthritis.
Effect of atorvastatin on knee cartilage volume in patients with symptomatic knee osteoarthritis: results from a randomised placebo-controlled trial.Arthritis Rheumatol
To determine whether atorvastatin compared to placebo slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis in a multicentre, randomised, double-blind, placebo-controlled trial.
Participants aged 40-70 years were randomised to oral atorvastatin 40 mg (n=151) or matching placebo (n=153) once daily. Primary endpoint: annual percentage change in tibial cartilage volume assessed using magnetic resonance imaging (MRI) over two years. Pre-specified secondary endpoints: progression of cartilage defects and bone marrow lesions assessed using MRI, and change in Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness and function over two years.
Of 304 participants (mean age 55.7 years, 55.6% female), 248 (81.6%) completed the trial. Annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (-1.66% vs. -2.17%, difference 0.50%, 95%CI -0.17% to 1.17%). There were no significant differences in progression of cartilage defects (odds ratio 0.86, 95%CI 0.52-1.41) or bone marrow lesions (odds ratio 1.00, 95%CI 0.62-1.63), change in pain [-36.0 vs. -29.5, adjusted difference -2.7, 95%CI -27.1 to 21.7), stiffness (-14.2 vs. -11.8, adjusted difference -0.2, 95%CI -12.2 to 11.8), or function [-89.4 vs. -87.5, adjusted difference 0.3, 95%CI -83.1 to 83.6). Incidence of adverse events was similar in atorvastatin (n=57, 37.7%) and placebo (n=52, 34.0%) groups.
Oral atorvastatin 40 mg once daily, compared with placebo, did not significantly reduce cartilage volume loss over two years in patients with symptomatic knee osteoarthritis. These findings do not support use of atorvastatin in the treatment of knee osteoarthritis.
Expert Perspective: Management of refractory inflammatory myopathy.Arthritis Rheumatol
The idiopathic inflammatory myopathies (IIM) are chronic disorders characterized by inflammation in skeletal muscle but also in other organs like t...
Erosive Hand Osteoarthritis: Incidence and Predictive Characteristics among Participants in the Osteoarthritis Initiative.Arthritis Rheumatol
To evaluate age, sex, race, osteoarthritis severity, metabolic factors, and bone health as risk factors for incident erosive hand osteoarthritis (EHOA) at baseline and over 48-month period.
This study was a longitudinal cohort design including participants from the Osteoarthritis Initiative with complete hand radiographs from baseline and 48-month visits who were eligible at baseline for incident EHOA. Individuals were classified as having EHOA if they had Kellgren-Lawrence (KL) grade≥2 in at least one interphalangeal joint on two different fingers and central erosion in at least one joint.
Of the 3365 individuals identified without prevalent EHOA at baseline, 86 (2.6%) developed EHOA during the 48-month period. Risk factors included being older [relative risk (RR) per standard deviation=0.76 (95% confidence interval 0.59, 0.98)], female [RR=1.73 (1.05, 2.85)], greater osteoarthritis severity (sum of KL grade 13.9 vs. 5.3, p<0.001) and less cortical width (1.38 vs 1.52 mm, p<0.001). After 48 months, people who developed EHOA were characterized by greater progressions of radiographic osteoarthritis (i.e., joint space narrowing, KL grade progression [RRs = 1.35 to 1.9] and loss of cortical thickness [RR = 1.23], adjusted for age, sex, race, body mass index, and baseline osteoarthritis severity (sum KL scores).
These findings present EHOA as a disorder of advanced age and female sex, strongly associated with severity of articular structural damage and its progression. Individuals who develop EHOA have thinner bones prior to EHOA development and as it progresses, suggesting EHOA as a disorder of skeletal frailty.
Multiple Pulmonary artery aneurysms in Hughes-Stovin syndrome.Arthritis Rheumatol
An eighteen-year-old male presented with fever of one month duration with on-and-off hemoptysis, dry cough, joint pains and myalgia. There were no ...
ICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the , MIF Immune Susceptibility Locus.Arthritis Rheumatol
Macrophage migration inhibitory factor (MIF) is an inflammatory and neurorendocrine mediator that counter-regulates glucocorticoid immunosuppression. MIF polymorphisms, which comprise a variant promoter microsatellite (-794 CATT5-8 ), are linked genetically to autoimmune disease severity and to glucocorticoid resistance. While invasive stimuli increase MIF expression, MIF also is upregulated by glucocorticoids, which serves as a physiologic regulator of the inflammatory responses. This study defined interactions between the MIF promoter, the glucocorticoid receptor (GR), and the transcription factor ICBP90, which binds to the promoter in a -794 CATT5-8 -length dependent manner, to regulate MIF transcription.
Interactions between ICBP90, GR, and AP-1 with MIF -794 CATT5-8 promoter constructs were assessed by co-immunoprecipitation, Western blotting, and genetic knockdown. Nuclear co-localization was performed using anti-transcription factor antibodies and confocal microscopy of glucocorticoid-treated cells. MIF transcription was studied in CEM-C7 T cells and the impact of the MIF -794 CATT5-8 microsatellite variation confirmed in peripheral blood T cells and in rheumatoid synovial fibroblasts of defined MIF genotype. Functional interactions were quantified by apoptosis and apoptotic signaling in high- and low-genotypic MIF expressing human cells.
We defined functional interactions between the transcription factors ICBP90, the GR, and AP-1 that upregulated MIF transcription in a -794 CATT5-8 length-dependent manner. Experimental reduction in ICBP90, GR, or AP-1 decreased MIF expression and increased glucocorticoid sensitivity, leading to enhanced apoptosis in T lymphocytes and in rheumatoid synovial fibroblasts.
These findings support a mechanism for genetic variation of glucocorticoid-regulated MIF transcription with implications for autoimmune disease severity and glucocorticoid responsiveness.
Non-serious infections in patients with rheumatoid arthritis; results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.Arthritis Rheumatol
To describe the frequency and predictors of non-serious infections (NSI) and compare incidence across biologics within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA).
The BSRBR-RA is a prospective observational cohort study. NSI was defined as infections that did not require hospitalisation or intravenous therapy. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered 'at risk' from the date of commencing biologic for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, B cell depletion or csDMARD only. A multiple-failure Cox model was used with multivariable adjustment. Missing data were addressed using multiple imputation.
There were 17,304 NSI in 8145 patients, with an event rate of 27.0 per person per year (95%CI 26.6 to 27.4). Increasing age, female gender, comorbidity, corticosteroid therapy, higher DAS28 and HAQ-DI were associated with an increased risk of NSI. There was a statistically significant reduction in NSI risk with csDMARD compared with biologics. Compared to TNFi, IL-6 inhibition and rituximab had a higher NSI risk [adjusted HR 1.45 (95% CI 1.29 to 1.63) and adjHR 1.28 (1.14 to 1.45)] respectively, whilst the csDMARD cohort had a lower risk [adjHR 0.64 (95% CI 0.59 to 0.70)]. Within the TNFi class, adalimumab had a higher NSI risk than etanercept [adjHR 1.11 (95%CI 1.05 to 1.17)].
NSI occur frequently in RA and predictors mirror those reported with serious infections. All biologics associate with a greater risk, with differences between agents. Whilst unmeasured confounding must be considered, the magnitude of effect is large and a relationship between NSI and targeted immunomodulatory therapy likely exists.
Moving the Goalpost Towards Remission: The Case for Combination Immunomodulatory Therapies in Psoriatic Arthritis.Arthritis Rheumatol
Following the pivotal manuscript that outlined unique disease features half a century ago, investigators in the field of psoriatic arthritis (PsA) ...
Presidential address 2020.Arthritis Rheumatol
It seemed as though it was a year like any other year. But in December 2019 a new virus, the SARS-CoV-2 virus, was identified. In less than 9 month...
Body fat composition and risk of rheumatoid arthritis: Mendelian randomisation study.Arthritis Rheumatol
Observational studies showed obesity (defined using BMI) to be associated with rheumatoid arthritis (RA) risk, but its causal role remains unclear....