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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Predictive value of MRI in patients with juvenile idiopathic arthritis in clinical remission.

Arthritis Care Res

To define the prevalence of MRI subclinical synovitis in a large cohort of JIA patients in clinical remission and to evaluate its predictive value in terms of disease flare and joint deterioration.

Ninety patients with clinically inactive JIA who underwent a contrast-enhanced (CE) MRI of a previously affected joint were retrospectively included. Each joint was evaluated for synovitis, tenosynovitis and bone marrow oedema (BMO). Baseline and follow-up radiographs were assessed to evaluate structural damage progression.

CE-MRI was acquired in 45 wrists, 30 hips, 13 ankles and 2 knees. Subclinical synovitis was detected in 59/90 (65.5%) patients and BMO in 42/90 (46.7%) patients. Fifty-seven out of 90 (63.3%) patients experienced a disease flare during follow-up. Forty-four out of 59 (74.6%) patients with subclinical synovitis experienced a disease flare versus 13/31 (41.9%) patients with no residual synovitis on MRI (p=0.002). The presence of subclinical synovitis was the best predictor of disease flare on multivariable regression analysis (HR= 2.45; p=0.003). Baseline and follow-up radiographs were available for 54 patients; 17/54 (31.5%) patients experienced radiographic damage progression. BMO (HR=4.40; p=0.045) and age > 17 years (HR= 3.51; p=0.04) were strong predictors of joint damage progression in the multivariable analysis.

MRI-detected subclinical inflammation was present in a large proportion of patients with JIA despite clinical remission. Subclinical synovitis and BMO have been shown to play a role in predicting the risk of disease relapse and joint deterioration, with potential implications for patients' management.

Comprehension, Utility, and Acceptability of a Multi-Domain Physical Functioning Report for Systemic Lupus Erythematosus Patients and Their Providers.

Arthritis Care Res

Patient-provider discussions about functioning are often outside the scope of usual care for systemic lupus erythematosus (SLE), and tools to facilitate such discussions are lacking. We assessed the comprehension, utility, and acceptability of a novel, individualized functioning report, the purpose of which is to facilitate patient-provider communication about functioning, in a predominantly Black SLE patient population.

Individualized reports (including sections with pictorial representations of participants' measured activities of daily living, falls, physical performance, perceived physical functioning, and community mobility from a previous pilot study visit) and surveys were emailed or mailed to 59 SLE patients. Ease of interpretation was dichotomized ("very easy" vs. all other responses). Utility and acceptability were assessed by items relating to usefulness for care planning and comfort with discussing the report.

Among 47 (79.7%) SLE patients who completed the survey (78.7% Black, 91.5% female, mean age=49.6), reported ease of interpretation ranged from 70.2% to 85.1% across the report sections. Ease of interpretation was lower among those who were older, Black, and female and who had lower cognitive scores (P>0.05 for all). Most reported that physical functioning domains of the report were useful for treatment or other care planning (70.2-80.5%) and that they felt comfortable discussing the report with a healthcare provider (93.2-100%).

We found that a novel functioning report for SLE patients was associated with high comprehension, utility, and acceptability. Future studies can help determine how an individualized functioning report could improve patient-provider communication in the clinic setting.

REPLY.

Arthritis Care Res

Dr. Miller's point is well-taken. It is because there has been a lack of existing data about differential efficacy among NSAIDs that we took the ap...

Determining in which pre-arthritis stage HLA-shared epitope alleles and smoking exert their effect on the development of rheumatoid arthritis.

Annals of the Rheumatic Diseases

The human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking are the most prominent genetic and environmental risk factors for rheumatoid arthritis (RA). However, at which pre-arthritis stage (asymptomatic/symptomatic) they exert their effect is unknown. We aimed to determine whether HLA-SE and smoking are involved in the onset of autoantibody positivity, symptoms (clinically suspect arthralgia (CSA)) and/or progression to clinical arthritis.

We performed meta-analyses on results from the literature on associations of HLA-SE and smoking with anti-citrullinated protein antibodies (ACPAs) in the asymptomatic population. Next, we studied associations of HLA-SE and smoking with autoantibody positivity at CSA onset and with progression to clinical inflammatory arthritis (IA) during follow-up. Associations in ACPA-positive patients with CSA were validated in meta-analyses with other arthralgia cohorts. Analyses were repeated for rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and anti-acetylated protein antibodies (AAPA).

Meta-analyses showed that HLA-SE is not associated with ACPA positivity in the asymptomatic population (OR 1.06 (95% CI:0.69 to 1.64)), whereas smoking was associated (OR 1.37 (95% CI: 1.15 to 1.63)). At CSA onset, both HLA-SE and smoking associated with ACPA positivity (OR 2.08 (95% CI: 1.24 to 3.49), OR 2.41 (95% CI: 1.31 to 4.43)). During follow-up, HLA-SE associated with IA development (HR 1.86 (95% CI: 1.23 to 2.82)), in contrast to smoking. This was confirmed in meta-analyses in ACPA-positive arthralgia (HR 1.52 (95% CI: 1.08 to 2.15)). HLA-SE and smoking were not associated with RF, anti-CarP or AAPA-positivity at CSA onset. Longitudinally, AAPA associated with IA development independent from ACPA and RF (HR 1.79 (95% CI: 1.02 to 3.16)), anti-CarP did not.

HLA-SE and smoking act at different stages: smoking confers risk for ACPA and symptom development, whereas HLA-SE mediates symptom and IA development. These data enhance the understanding of the timing of the key risk factors in the development of RA.

TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis.

Annals of the Rheumatic Diseases

Innate lymphoid cells-2 (ILC2) were shown to be involved in the development of lung or hepatic fibrosis. We sought to explore the functional and phenotypic heterogeneity of ILC2 in skin fibrosis within systemic sclerosis (SSc).

Blood samples and skin biopsies from healthy donor or patients with SSc were analysed by immunostaining techniques. The fibrotic role of sorted ILC2 was studied in vitro on dermal fibroblast and further explored by transcriptomic approach. Finally, the efficacy of a new treatment against fibrosis was assessed with a mouse model of SSc.

We found that ILC2 numbers were increased in the skin of patients with SSc and correlated with the extent of skin fibrosis. In SSc skin, KLRG1- ILC2 (natural ILC2) were dominating over KLRG1+ ILC2 (inflammatory ILC2). The cytokine transforming growth factor-β (TGFβ), whose activity is increased in SSc, favoured the expansion of KLRG1- ILC2 simultaneously decreasing their production of interleukin 10 (IL10), which regulates negatively collagen production by dermal fibroblasts. TGFβ-stimulated ILC2 also increased myofibroblast differentiation. Thus, human KLRG1- ILC2 had an enhanced profibrotic activity. In a mouse model of SSc, therapeutic intervention-combining pirfenidone with the administration of IL10 was required to reduce the numbers of skin infiltrating ILC2, enhancing their expression of KLRG1 and strongly alleviating skin fibrosis.

Our results demonstrate a novel role for natural ILC2 and highlight their inter-relationships with TGFβ and IL10 in the development of skin fibrosis, thereby opening up new therapeutic approaches in SSc.

Treating the skin with biologics in patients with psoriasis decreases the incidence of psoriatic arthritis.

Annals of the Rheumatic Diseases

To compare the incidence of psoriatic arthritis (PsA) in patients with psoriasis (PsO) according to different treatments for their skin: topics/no treatment, conventional disease-modifying antirheumatic drugs (DMARDs) (cDMARDs) or biological DMARDs (bDMARDs).

Patients with PsO without PsA followed at a university hospital were included in this retrospective cohort study. Patients were classified according to their treatment in topics (topics, phototherapy or no treatment), cDMARDs (methotrexate and cyclosporine) and bDMARDs (tumour necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i) and IL-12-23i ((interleukin (IL) 12/IL-23 inhibitor))) groups. Incident cases of PsA were attributed to one treatment if developed during the administration of that treatment. A Cox proportional hazards model was used to evaluate the adjusted risk of PsA development by treatment group.

1719 patients with PsO contributed a total of 14 721 patient/years (py). 1387 (81%) patients were in the topics, 229 (13%) in cDMARDs and 103 (6%) in the bDMARDs group. During follow-up, 239 patients (14%) developed PsA (231 under topics, six under cDMARDs and two under bDMARDs). Global incidence was 1.6 per 100 py. The risk of developing PsA in patients with PsO treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94; p=0.0111), compared with topics, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96; p=0.1007). Adjusted Cox proportional hazards regression analysis showed that male sex, nail involvement and higher body max index were associated with increased risk of developing PsA, while biologics use was protective (HR: 0.19; 95% CI 0.05 to 0.81).

Treatment with biologics in patients with PsO reduced the risk of PsA development.

Variants on the UBE2L3-YDJC autoimmune disease risk haplotype increase UBE2L3 gene expression by modulating CTCF and YY1 binding.

Arthritis Rheumatol

Genetic variants spanning the ubiquitin-conjugating enzyme E2 L3 (UBE2L3) gene are associated with increased expression of the UBE2L3-encoded E2 ubiquitin-conjugating enzyme, UbcH7, that facilitates activation of proinflammatory NF-κB signaling, and susceptibility to autoimmune diseases. This study aims to delineate how genetic variants carried on the UBE2L3-YDJC autoimmune risk haplotype function to drive hypermorphic UBE2L3 expression.

We used bioinformatic analyses, electrophoretic mobility shift assays, and luciferase reporter assays to identify and functionally characterize allele-specific effects of risk variants positioned in chromatin accessible regions of immune cells. Chromatin conformation capture (3C)-qPCR, ChIP-qPCR, and siRNA knockdown assays were performed on patient-derived EBV-transformed B cells homozygous for the UBE2L3-YDJC non-risk or risk haplotype to determine if the risk haplotype increases UBE2L3 expression by altering the regulatory chromatin architecture in the region.

Five of the seven prioritized variants demonstrated allele-specific increases in nuclear protein binding affinity and regulatory activity. HiChIP and 3C-qPCR uncovered a long-range interaction between the UBE2L3 promoter (rs140490, rs140491, rs11089620) and downstream YDJC promoter (rs3747093) that was strengthened in the presence of the UBE2L3-YDJC risk haplotype, and correlated with the loss of CTCF binding and gain of YY1 binding at the risk alleles. Depleting YY1 by siRNA disrupted the long-range interaction between the two promoters and reduced UBE2L3 expression.

The UBE2L3-YDJC autoimmune risk haplotype increases UBE2L3 expression through strengthening a YY1-mediated interaction between the UBE2L3 and YDJC promoters.

Platelet phagocytosis via PSGL1 and accumulation of microparticles in systemic sclerosis.

Arthritis Rheumatol

It is unclear why activated platelets and platelet-derived microparticles (µPs) accumulate in the blood of patients with systemic sclerosis (SSc). Here we investigated whether defective phagocytosis might contribute.

Platelet-neutrophil interaction, phagocytosis, P-selectin, PSGL-1, HMGB1 expression and distribution on platelet and µPs, the concentration of byproducts of NET generation/catabolism were assessed by flow cytometry and immunochemistry in 81 donors. 25 patients had SSc, 26 patients stable coronary artery atherosclerosis (CAD). 30 sex- and age-matched healthy volunteers served as controls. Lung parenchyma and microvasculature were assessed in NSG mice after µPs injection in the tail vein.

Activated P-selectin+ platelets and platelet-derived-HMGB1+ µPs accumulate in the blood of SSc patients and not of controls. Patients with CAD, a vasculopathy independent of systemic inflammation, had less P-selectin+ platelets and negligible µPs. The expression of the receptor for P-selectin, PSGL-1 in SSc neutrophils was significantly decreased, raising the possibility that phagocytes fail to recognize and phagocytose activated platelets, which in turn might keep releasing µPs. In support, SSc neutrophils did not contain platelets, consistently present within CAD neutrophils. HMGB1+ µPs elicit the generation of NETs, which were detected in the plasma of SSc patients only. P-selectin/PSGL-1 interaction resulted in platelet phagocytosis in vitro and influenced the µPs ability to elicit NETs, endothelial activation and migration of leukocytes through pulmonary microvasculature in mice.

The clearance of activated platelets via PSGL-1 limits undesirable effects of µPs-elicited neutrophil activation. This balance is disrupted in patients with SSc. Its reconstitution might curb vascular inflammation and prevent fibrosis.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) Syndrome, A Central Nervous System Vasculitis Mimic.

Arthritis Rheumatol

A 37-year-old male with diabetes mellitus and hypertension presented with severe headache. Over a one-month period, magnetic resonance imaging show...

Defective early B cell tolerance checkpoints in patients with systemic sclerosis allow the production of self-antigen-specific clones.

Arthritis Rheumatol

Early selection steps preventing autoreactive naïve B cell production are often impaired in patients with autoimmune diseases, but central and peripheral B cell tolerance checkpoints have not been assessed in patients with systemic sclerosis (SSc).

Using an in-vitro PCR-based approach that allows the expression of recombinant antibodies cloned from single B cells, we tested the reactivity of antibodies expressed by 212 CD19+ CD21-/lo CD10+ IgMhi CD27- new emigrant/transitional and 190 CD19+ CD21+ CD10- IgM+ CD27- mature naïve B cells from ten patients with SSc.

Patients with SSc displayed elevated proportions of polyreactive and anti-nuclear new emigrant/transitional B cells that recognize topoisomerase I when compared to healthy donors, suggesting defective central B cell tolerance contributes to the production of serum autoantibodies characteristic of the disease. Frequencies of autoreactive mature naïve B cells were also significantly increased in SSc patients and revealed an impaired peripheral B cell tolerance checkpoint.

Defective counterselection of developing autoreactive naïve B cells in SSc leads to the production of self-antigen specific B cells that may secrete autoantibodies and allow the formation of immune complexes, which promote fibrosis in SSc.

Risk of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis initiating interleukin 17 inhibitors: a nationwide population-based study using the French national health data system.

Arthritis Rheumatol

To investigate whether IL17-inhibitors (IL17i) initiation in real life is associated with a higher risk of inflammatory bowel disease (IBD) in patients with psoriasis (PsO), psoriatic arthritis and ankylosing spondylitis (PsA/AS).

This nationwide cohort study involved the French national health data system database. All adults with PsO and PsA/AS who were new-users of IL17i during 2016-2019 were included. Two non-exposed PsO and PsA/AS population were included: new-users of (1) apremilast and (2) etanercept. End of follow-up was September 30, 2019. The primary end-point was an occurrence of IBD in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models.

A total of 16,793 IL17i new-users (mean age 48.4±13 years; 46% men); 20,556 apremilast new-users (mean age 52.5±14.6 years; 53% men); and 10,245 etanercept new-users (mean age 46.3±15 years; 44% men) were included. Previous systemic treatements were closer between IL17i and etanercept compared with apremilast. IBD occurred in 132 cases: 72 (0.43%) in IL17i new-users, 11 (0.05%) in apremilast new-users and 49 (0.48%) in etanercept new-users. Most IBD cases occurred after 6 months of exposure (82%, 55% and 76% respectively). After propensity score weighting, the risk of IBD was significantly greater with IL17i than apremilast (HRw 3.8, 95%CI 2.1-6.8). No difference was observed between IL17i and etanercept new-users (HRw 0.8, 95%CI 0.5-1.2).

Compared with patients initiating etanercept that displayed the same severity of the underlying disease, IL17i new-users did not present a higher risk of IBD. These results need to be confirmed in other large databases.

International Consensus For The Dosing Of Corticosteroids In Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis.

Arthritis Rheumatol

To develop a Standardized Steroid dosing Regimen (SSR) by physicians treating childhood-onset systemic lupus erythematosus (cSLE) complicated by lupus nephritis (LN), using consensus formation methodology.

Parameters influencing corticosteroid (CS) dosing were identified (Step-1). Data from children with proliferative LN were used to generate Patient Profiles (PP) (Step-2). Physicians rated change in activity of renal and extra-renal cSLE between two consecutive visits and proposed CS dosing (Step-3). Using PP ratings, the SSR was developed (Step-4) with refinements achieved in a physician focus group (Step-5). A second type of PP describing cSLE course for ≥4 months since kidney biopsy were rated to validate the SSR-recommended oral and intravenous CS-dosages (Step-6). PP adjudication was based on majority ratings for both renal and extra-renal disease courses, and consensus level was set at 80%.

Degree of proteinuria, estimated glomerular filtration rate, change in renal and extra-renal disease activity, and time since kidney biopsy influenced CS dosing (Steps-1/2). Considering these parameters in 5,056 PP-ratings from 103 raters, and renal and extra-renal course definitions, CS-dosing rules of the SSR were developed (Steps-3-5). Validation of the SSR for up to 6 months post kidney biopsy was achieved with 1,838 PP-ratings from 60 raters who achieved consensus for oral and intravenous CS dosage as per the SSR (Step-6).

The SSR represents an international consensus on CS dosing for use in patients with cSLE and proliferative LN. The SSR is anticipated to be used for clinical care and standardize CS-dosage during clinical trials.