Chemerin/ChemR23 pathway: a system beyond chemokines

Chemerin is a chemokine that, through the engagement of its counter-receptor, ChemR23, attracts pro-inflammatory cells. However, chemerin has been shown to play other functions and a recent study by Berg and colleagues demonstrates that chemerin/ChemR23 is a system beyond chemokines. Human articular chondrocytes produce chemerin and express ChemR23, and upon stimulation with recombinant chemerin increase the production of pro-catabolic cytokines and metalloproteinases. The latter are up-regulated in osteoarthritic cartilage and cause extracellular matrix breakdown. Since an increase of chemerin in fat tissue and serum of obese patients has been reported, this new feature of chemerin may represent a functional link between obesity and osteoarthritis

Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: A case series

Background: Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. Case presentations. The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be stopped; the patient remained in drug-free remission. Conclusion: This report includes the first published case of the use of adalimumab in a child aged <3 years. Our clinical experience further supports the use of biologic therapy for the management of juvenile idiopathic arthritis and uveitis in children as young as two years of age. © 2014 La Torre et al.; licensee BioMed Central Ltd

Radiomics to predict the mortality of patients with rheumatoid arthritis-associated interstitial lung disease: A proof-of-concept study

OBJECTIVES: Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients. METHODS: High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables. RESULTS: We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36–120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56–55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05–0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06–0.82) and the flatness (HR 0.42, 95% CI 0.18–0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82–2.83) was also retained as a confounder. CONCLUSION: Radiomic analysis may predict RA-ILD patients’ mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease

Phenotyping of chondrocytes from human osteoarthritic cartilage: chondrocyte expression of beta integrins and correlation with anatomic injury

Chondrocyte-ECM (extracellular matrix) interactions are believed to play a pivotal role in the development and metabolic homeostasis of articular cartilage. Cell surface adhesion molecules have been reported to modulate chondrocyte binding to ECM (collagen, fibronectin, laminin) and they also act as transducers of critical signals in many biological processes such as growth, differentiation, migration and matrix synthesis. Recently, it has been shown that normal human articular chondrocytes strongly express beta1 integrins, which are constituted by a common chain (beta1) and a variable alphachain, but the behaviour of these molecules in human osteoarthritic cartilage has not been extensively investigated. We studied the expression of beta integrins (beta1-5, alpha1-6, av chains), LFA-1, ICAM-1 and CD44, on freshly isolated chondrocytes obtained from 10 osteoarthritic patients undergoing surgical knee replacement. Chondrocytes were isolated by enzymatic digestion from three zones of each articular cartilage with a differing degree of macroscopic and microscopic damage. Integrin expression and cell cycle analysis were carried out by flowcytometry. Chondrocytes from costal cartilages of 5 human foetuses were also studied. Chondrocytes from osteoarthritic cartilage expressed high levels of beta1 integrin and, at different percentages, all the alphachains. The alphachain most frequently expressed was alpha1, foilowed by alpha3, alpha5, alpha2, alphav. Integrin expression decreased from the least to the most damaged zone of articular cartilage and cell cycle analysis showed that proliferating chondrocytes (S phase) were prevalent on the latter zone. beta2, beta3, beta2, beta5, CD44, LFA-1/ICAM-1 complex were very low expressed. Fetal chondrocytes strongly expressed beta1 and beta5 chains. These data provide evidence to show that integrin expression on human chondrocytes changes in osteoarthritis and suggest that perturbations of chondrocyte-ECM signalling occur in the development of the disease. The different pattern of expression of beta1 and beta5 chains on adult and fetal chondrocytes leads to speculate that integrins play a key role in control of cartilage morphogenesis and differentiation

Sarcopenia in Patients with Rheumatic Diseases: Prevalence and Associated Risk Factors

The prevalence of sarcopenia in rheumatic diseases has been evaluated in single diseases using various diagnostic approaches, generating conflicting data on the pathogenetic mechanism(s). Herein, we evaluated both muscle mass index (MMI) and muscle strength to assess sarcopenia and presarcopenia in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Moreover, we evaluated the possible impact of disease/patient-related characteristics, therapeutic regimens, and nutritional aspects on sarcopenia. The present study included 168 patients of both genders, aged 40⁻75 years. All patients underwent a nutritional evaluation, physical activity level assessment, rheumatologic evaluation, and an MMI and muscle strength assessment. The prevalence of sarcopenia was about 20% in all the three rheumatologic diseases, whereas presarcopenia was significantly different in RA, PsA and AS (p = 0.006). At multivariate analysis, only age ≥60 years and the presence of a disability were associated with a significantly increased risk of sarcopenia (p = 0.006 and p = 0.01, respectively), while a higher C-reactive protein did not reach statistical significance. Sarcopenia is similar in RA, PsA and AS, whereas presarcopenia significantly differs in these three diseases. Disease activity/inflammation and nutritional aspects do not influence sarcopenia, while age ≥60 years and the presence of a disability significantly increase the risk of sarcopenia

Intravitreal Dexamethasone Implant as an Adjunct Weapon for Severe and Refractory Uveitis in Behçet's Disease

Background: The evidence on the use of dexamethasone implants in the treatment of Behçet’s disease (BD)-related uveitis is limited to a few cases. Objectives: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. Methods: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits. Results: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. Conclusions: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs

Extracorporeal shock waves down-regulate the expression of interleukin-10 and tumor necrosis factor-alpha in osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and particularly on the expression of IL-10, TNF-alpha and beta1 integrin.</p> <p>Methods</p> <p>Human adult articular cartilage was obtained from 9 patients (6 male and 3 females), with primary knee osteoarthritis (OA), undergoing total joint replacement and from 3 young healthy donors (HD) (2 males, 1 female) with joint traumatic fracture. After isolation, chondrocytes underwent ESW treatment (electromagnetic generator system, MINILITH SL1, STORZ MEDICAL) at different parameters of impulses, energy levels and energy flux density. After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta₁integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry.</p> <p>Results</p> <p>At baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies.</p> <p>Conclusion</p> <p>Our study confirmed that osteoarthritic chondrocytes express low beta₁integrin and high TNF-alpha and IL-10 levels. Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. However, further in vivo and in vitro studies are necessary to establish if ESW can represent a viable option in the treatment of OA.</p