Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 34746971 | Evaluation of retinal microvascular structures by optical coherence tomography angiography | 2022 Apr | OBJECTIVES: There are insufficient data in the literature on how retinal capillaries are affected in primary Sjögren's syndrome (PSS). The aim of this study was to evaluate the retinal capillary density (CD) in PSS using optical coherence tomography angiography (OCTA). METHODS: In this case-control study, 26 eyes from 13 PSS patients and 39 eyes from 20 healthy controls (HCs) were included. The CD in the regions of the superior capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillaries (RPC) as well as assessment parameters of the foveal avascular zone (FAZ) were examined by OCTA. RESULTS: The mean CD (%) was 50.2 ± 4.2 and 50.5 ± 3.4 in the SCP (p = 0.904), 49.2 ± 7.5 and 53.9 ± 5.7 in the DCP (p = 0.006) and 50.8 ± 2.1 and 49.8 ± 2.2 in the RPC (p = 0.088) regions in patients with PSS and HCs, respectively. In patients with PSS and HCs, the mean sizes of the FAZ were 0.243 ± 0.07 mm(2) and 0.283 ± 0.13 mm(2) (p = 0.142), and the mean sizes of the non-flow area were 0.480 ± 0.11 mm(2) and 0.509 ± 0.13 mm(2), respectively (p = 0.359). The correlation coefficients (Rho) of retinal CD in the SCP, DCP and RPC regions with disease duration were - 0.545 (p = 0.004), - 0.389 (p = 0.050) and - 0.795 (p < 0.001), respectively. CONCLUSION: The retinal CD in PSS is lower than that in the healthy population in deep retinal capillaries, and retinal CD shows a negative correlation with disease duration in PSS. CLINICAL TRIALS REGISTRATION: This study was not registered to clinicaltrials.gov. | |
| 34100160 | Sjögren's syndrome: a systemic autoimmune disease. | 2022 Feb | Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options. | |
| 33510043 | Normal salivary gland ultrasonography could rule out the diagnosis of Sjögren's syndrome | 2021 Jan | OBJECTIVE: To evaluate the relevance of salivary gland ultrasound (SGUS) and its place in the diagnostic algorithm in patients referred with dry syndrome (DS) for a suspicion of Sjögren's syndrome (SS). METHODS: We included all patients assessed at our dedicated DS clinic from June 2015 to September 2019 for which a SGUS has been carried out. Images were read blindly and the worst salivary gland was scored according to OMERACT classification. Clinical features, disease activity and treatments were collected. RESULTS: 337 patients were seen from June 2015 to September 2019. 269 patients underwent SGUS. 77 patients were diagnosed with SS and 192 did not meet the ACR/EULAR criteria for SS: non-Sjögren's DS (NSDS). Of these 192 patients, 60 had another possible cause of DS, and 132 patients were diagnosed with SAPS (sicca, asthenia, polyalgia syndrome).SGUS abnormalities were significantly higher in patients with SS versus NSDS: 51% vs 8% for a score ≥2 (p<0.0001), and 43% vs 3% for a score ≥3 (p<0.0001). SGUS score ≥2 had a specificity (Sp) of 91%, sensitivity (Se) of 57%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 82% for SS diagnosis. SGUS's characteristics in SSA-negative patients were similar to the whole population (Se=42%, Sp=91%, PPV=42%, NPV=92%). The high specificity and NPV in this population could avoid labial salivary gland biopsy (LSGB) in SSA-negative patients with normal SGUS (186 patients, 69%). CONCLUSION: SGUS is useful for SS diagnosis. If anti-SSA antibodies are negative and SGUS score <2, the diagnosis of SS is very improbable and LSGB could be avoided. | |
| 34126828 | Interleukin-6 inhibition: a therapeutic strategy for the management of adult-onset Still's | 2022 Jan | INTRODUCTION: Patients with adult-onset Still's disease have markedly elevated serum levels of proinflammatory cytokines, such as IL-1β, IL-6, and IL-18, suggesting the potential of these molecules as therapeutic targets. IL-6 accelerates macrophage and cytotoxic T-cell differentiation and neutrophil and macrophage chemotaxis and is one of the most important cytokines in the pathogenesis of adult-onset Still's disease. AREAS COVERED: The review summarizes the importance of IL-6 in the pathogenesis of adult-onset Still's disease and clinical aspects of IL-6 inhibition from retrospective and prospective studies. EXPERT OPINION: Adult-onset Still's disease is a systemic inflammatory disease of unknown etiology and characterized by elevated various proinflammatory cytokines. In particular, serum concentrations of IL-6 is significantly high in patients with active adult-onset Still's disease, and many case reports, cohort studies and one randomized, placebo-controlled trail have shown the efficacy of IL-6 blockade in patients with adult-onset Still's disease who were refractory to glucocorticoids and other immunosuppressive treatments. IL-6 inhibition is effective for both systemic and joint manifestations with arthritis improving slowly. There is still a concern over the triggering of macrophage activation syndrome; however, the IL-6 inhibition strategy has introduced better management of adult-onset Still's disease. | |
| 33547856 | Interpretation of the mucous plug through sialendoscopy. | 2022 Mar | OBJECTIVE: The purpose of this manuscript is to highlight the behaviour of mucus inside the ducts of the major salivary glands, in presence of typical pathologies, through images obtained with sialendoscopy. SUBJECT: The authors present and comment on some sialendoscopies that show mucous plug in the ducts of the major salivary glands. RESULTS: In primary Sjogren's syndrome, mucous plugs confirm the qualitative anomaly of the mucins and acidification saliva. Instead, salivary calculations behave like foreign bodies that generate mechanical pressure and friction on the duct walls of major salivary glands, so mucus deposits in the duct in its defence; in case of infected stone, mucous plugs are formed also with the function of protecting the ducts from the aggression of germs. During sialadenitis, there is a conflict between mucus and bacteria which explains sialendoscopic evidence such as white duct walls and mucous plugs. CONCLUSIONS: The study of the salivary ducts through sialendoscopy often confirms the clinical diagnosis or hypothesize it. During its execution, it is necessary not only to liberate the ducts of the major salivary glands but also analyse the appearance of the mucous plugs and the ductal walls as they are useful to guide the physician towards diagnosis. | |
| 32529559 | Renal disorders in rheumatologic diseases: the spectrum is changing (Part 1: connective ti | 2021 Aug | The kidney is frequently involved by autoimmune rheumatic diseases. The renal manifestations may be variable, ranging from asymptomatic proteinuria and microscopic haematuria to nephrotic syndrome and rapidly progressive glomerulonephritis or vasculitis. In a number of cases the kidney involvement is related to the treatment of the original disease and may represent a major cause of morbidity and mortality. Thus, it is important for nephrologists and rheumatologists to remember that dysfunction of the kidney may be part of the primary systemic disorder or consequence of its pharmacotherapy. In the first part of this review we will analyse the kidney involvement in four autoimmune connective tissue diseases: systemic lupus erythematosus, Sjögren syndrome, polymyositis/dermatomyositis, and systemic sclerosis. Renal disease is common in lupus and is a main cause of morbidity and mortality. About 10% of patients with Sjögren syndrome may present interstitial nephritis or, more rarely, glomerulonephritis. Myoglobinuria and acute kidney injury is a frequent complication of polymyositis. Renal disease is one of the most serious complications of systemic sclerosis and may present with a dramatic renal crisis, characterized by malignant hypertension, oligo-anuria, and microangiopathic thrombocytopenic anaemia. | |
| 33715009 | IL-6: from arthritis to CAR-T-cell therapy and COVID-19. | 2021 Sep 25 | Blockade of IL-6 function by an anti-IL-6 receptor (IL-6R) antibody (tocilizumab, trade name Actemra) has been shown to be effective for the treatment of chronic autoimmune inflammatory diseases including rheumatoid arthritis. Interestingly, treatment with tocilizumab has also been found to alleviate the cytokine storm induced by chimeric antigen receptor (CAR)-T-cell therapy. Patients with serious cases of coronavirus disease 2019 (COVID-19) exhibit cytokine release syndrome (CRS), which suggested that tocilizumab might be an effective therapeutic for serious cases of COVID-19. In the first part of this short review, the therapeutic effect of tocilizumab for the disease induced by IL-6 overproduction is described. CRS induced by CAR-T-cell therapy and COVID-19 is then discussed. | |
| 34111026 | Do eye diseases increase the risk of arthritis in the elderly population? | 2021 Jun 10 | There are very few longitudinal studies which have previously conducted an investigation into whether eye diseases are a risk for arthritis, and how this occurs. The study employed a variety of machine-learning algorithms, including random forest for investigating the risks, and to elucidate these underlying mechanisms by focusing on five aspects containing 389 characterized variables (mental health and wellbeing; physical health; disability, functional impairment and helpers; health behavior; and health measures). The study population included 8,423 individuals. Cataracts, glaucoma, and other eye diseases increase the likelihood of arthritis after two years by 131.8% (odds ratio (OR)=2.318, 95% confidence interval: 1.748 to 3.038), 123.1% (OR=2.231, 1.306 to 3.626), and 91.1% (OR=1.911, 1.501 to 2.415). Random forest corroborated that cataract contributes the most to arthritis risks after two years, followed by other eye diseases and glaucoma (mean Gini-index: 5.20, 2.11, 1.31). It is of note that the potential mechanisms of cataract-induced arthritis risk were elucidated extensively. The control domains of life quality, negative aging self-perceptions, mobility (steadiness, physical limitations, and muscle strength) and memory impairments, and sleep quality mediated the relationship between cataracts and arthritis significantly. Furthermore, different eye diseases affected osteoarthritis, rheumatoid arthritis, and other arthritis to varying degrees. Eye diseases increased the risk of arthritis, whereby cataracts were the most significant. Interventions which target these discovered mechanisms may be the preferred levers for reducing cataract-related arthritis risk. | |
| 34241658 | Neutrophil count reduction 1 month after initiating tocilizumab can predict clinical remi | 2021 Jul 9 | Neutropenia is a common adverse event of tocilizumab (TCZ) in rheumatoid arthritis (RA) patients; however, the association between the decrease in neutrophil counts and the TCZ clinical efficacy remains inconclusive. This study aimed to examine whether TCZ-induced neutrophil decrease at 1 month predicts clinical remission within 1 year. We reviewed medical records of RA patients initiating TCZ between May 2011 and September 2019 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating TCZ) and 1, 3, 6, and 12 months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. The ratio of neutrophil counts 1 month after initiating TCZ to those at baseline (neutrophil ratio) was also calculated. Among 255 TCZ-treated patients, 169 with valid CDAI and neutrophil counts were enrolled (with median age of 60 years and 79% females). Rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive in 75% and 83%, respectively, and 56% of the patients had concomitant methotrexate (median dose: 8 mg/week). Multivariate logistic regression analysis suggested baseline CDAI (odds ratio (OR) 0.96, p = 0.045), concomitant PSL (OR 0.42, p = 0.030), and the neutrophil ratio (OR 0.19, p = 0.011) as predictors of CDAI remission. Neutrophil ratio ≤ 0.8 was associated with achieving remission (Fisher's exact test, p = 0.02) with no apparent increase of severe infection. More than 20% reduction of neutrophil count 1 month after initiating TCZ predicts clinical remission within 1 year at an early treatment phase. | |
| 34303949 | An update on the pathogenic role of IL-6 in rheumatic diseases. | 2021 Oct | Interleukin (IL)-6 is a pleiotropic cytokine that is involved in the pathogenesis of various rheumatic diseases. Direct inhibition of the IL-6 pathway by an anti-IL-6 receptor or inhibiting the ligand itself has proved to be efficacious in the treatment of these diseases. Juvenile idiopathic arthritis, adult-onset Still's disease, large vessel vasculitis including giant cell arteritis and Takayasu disease, systemic sclerosis, and polymyalgia rheumatica respond well to IL-6 inhibition as expected. However, no clinically meaningful effect has been observed with regard to IL-6 blockade in ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus. This review discusses the current state of IL-6 targeting approaches in various rheumatic diseases other than rheumatoid arthritis. | |
| 34718430 | Development and validation of a prognostic model for leflunomide discontinuation with abno | 2021 Oct 27 | OBJECTIVE: To develop and validate a prognostic model for leflunomide discontinuation with abnormal blood-test results. METHODS: Data from CPRD Gold and Aurum were used for model development and external validation respectively. Participants prescribed leflunomide between 01/01/2007 and 31/12/2019 were followed-up from six-months after first GP-prescription to the earliest of date of outcome, death, 5-year follow-up or 31/12/2019. Candidate prognostic factors were ascertained using theory and data driven approaches. Penalised Cox regression was performed to develop the risk equation, followed by internal validation using 500-bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data for 1,487 and 2,329 participants contributing 3,140 and 5,246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy, and either cytopenia or elevated liver enzymes during first six months of shared-care leflunomide prescription were strong predictors of drug discontinuation with hazard ratio (95%CI) 4.39 (1.74 -11.06) and 3.06 (2.15 - 4.35), respectively. The unadjusted and optimism adjusted calibration slope in development data was 1.00 (95% CI 0.75-1.25) and 0.72 (95% CI 0.47-0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74-1.07). The model showed prognostic separation with optimism adjusted Royston D statistic of 0.73 (95% CI 0.44-1.02). CONCLUSION: We have developed and externally validated an easy-to-use prognostic model that may be used to risk-stratify monitoring for leflunomide toxicity and to make informed choices about risks when choosing treatments. | |
| 33741041 | The troubling liaison between cancer and metabolic syndrome in chronic inflammatory rheuma | 2021 Mar 19 | BACKGROUND: Several studies on community populations found that metabolic syndrome (MetS) is associated with higher risk for total incident cancer with a predisposition for specific types of cancer. These findings have never been analyzed in patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMD). We assessed prevalence/incidence and factors related to the development of cancer in a large cohort of these patients and evaluate whether MetS and its components were associated with cancer independent of traditional markers of inflammation. METHODS: Between March 2014 and April 2016, 474 patients with RMD involved in a cardiovascular primary prevention program were consecutively recruited into this ambispective (combination of retrospective/prospective) study. They underwent clinical, laboratory, and echocardiographic evaluations. MetS was diagnosed according to the ATPIII criteria. RESULTS: Duration of follow-up was 42 [18-60] months. Patients with a diagnosis of cancer (made before recruitment or during follow-up) were 46 (9.7%). Cancer was diagnosed in 22/76 patients (29%) with MetS and in 24/398 patients (6%, p < 0.001) without MetS; nearly two thirds of malignancies belonged to those traditionally related to MetS. MetS was the strongest cancer risk factor. Cancer was positively associated with the number of MetS components identified in each patient. Beyond MetS, cancer was associated to older age and increased inflammatory disease activity; this information allowed to build a simple performance indicator highly sensitive for cancer development. CONCLUSION: In light of our results, an increasingly accurate assessment of MetS would be required in patients with RMD as potential measure of clinical outcomes including the risk of cancer. | |
| 35459374 | Nintedanib in the treatment of systemic rheumatic disease-associated interstitial lung dis | 2021 Winter | Systemic rheumatoid diseases form a large group of entities with variable clinical picture and different involvement and degree of organ impairment. Respiratory tract represents major site of damage, with lung interstitium, pleura, pulmonary vasculature and airways possibly affected. In systemic sclerodermia and rheumatoid arthritis, lung disease is the most significant cause of morbidity and mortality. Breathing difficulties may either present as first symptoms of underlying rheumatoid disease or may appear at any time during the course of the disease. Rheumatologists should routinely screen their patients for possible lung impairment. Similarly, extrapulmonal signs should be assessed by pulmonologists in patients referred for dyspnea. Currently, novel antifibrotic therapy is available not only for patients with idiopathic pulmonary fibrosis (IPF), but also for selected group of patients with non-IPF progressive fenotype associated interstitial lung disease having solid evidence-based background. Interdisciplinary approach in terms of collaboration between pulmonologist and rheumatologist is of key importance as proper identification of possible candidates and early onset of therapy is crucial. | |
| 33650316 | Systematic Review of Outcomes and Patient Experience With Virtual Care in Rheumatoid Arthr | 2021 Mar 1 | OBJECTIVE: To conduct a systematic review on patient outcomes of virtual care compared to conventional care in rheumatoid arthritis (RA), including disease activity and patient experience. METHODS: A systematic search of Medline, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials was performed from database inception to March 19, 2020. Observational and randomized controlled trials (RCTs) describing the use of RA virtual care supplanting conventional visits and reporting on disease activity and/or patient experience were included. A narrative synthesis of results was conducted, as a meta-analysis was not possible due to heterogeneity of study designs and outcome reporting. RESULTS: A total of 352 studies were identified, and 6 were selected for final inclusion: 3 RCTs and 3 observational studies. Disease activity and patient experience were comparable between virtual and conventional care models. In addition, 1 RCT found no difference in observed outcomes between virtual care delivered by a rheumatologist and by a rheumatology nurse. Virtual care was found to have additional benefits for improved treatment adherence, maintenance of functional status, and quality of life. The overall risk of bias was low in 2 of 3 RCTs, but high in the observational studies. Study quality was limited by incomplete data reporting, lack of sample size justification, and sufficient timeframe to assess objectives. CONCLUSION: Limited evidence exists that virtual RA care is an acceptable alternative to conventional care, maintaining comparable patient outcomes and experience of care. Additional research into effective implementation strategies and long-term health system and patient outcomes of virtual care are needed. | |
| 33466633 | Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Pr | 2021 Jan 14 | The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost). The baseline features of 355 rheumatoid arthritis (RA) patients from the "treatment in the Rotterdam Early Arthritis CoHort" (tREACH) and the U-Act-Early trial were combined for analyses. The model performances were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves, 95% confidence intervals (95% CI), and sensitivity and specificity. Finally, the best performing model following feature selection was tested on 101 RA patients starting tocilizumab (TCZ)-monotherapy. Logistic regression (AUC = 0.77 95% CI: 0.68-0.86) performed as well as LASSO (AUC = 0.76, 95% CI: 0.67-0.85), random forest (AUC = 0.71, 95% CI: 0.61 = 0.81), and XGBoost (AUC = 0.70, 95% CI: 0.61-0.81), yet logistic regression reached the highest sensitivity (81%). The most important features were baseline DAS28 (components). For all algorithms, models with six features performed similarly to those with 16. When applied to the TCZ-monotherapy group, logistic regression's sensitivity significantly dropped from 83% to 69% (p = 0.03). In the current dataset, logistic regression performed equally well compared to machine-learning algorithms in the prediction of insufficient response to MTX. Models could be reduced to six features, which are more conducive for clinical implementation. Interestingly, the prediction model was specific to MTX (combination) therapy response. | |
| 34302162 | Inflammation and ROS in arthritis: management by Ayurvedic medicinal plants. | 2021 Sep 20 | Chronic joint inflammatory disorders like osteoarthritis and rheumatoid arthritis, which are manifested by joint dysfunction, show an upsurge in inflammation and oxidative stress. Although conventional anti-arthritic drugs are being used to relieve pain from arthritic symptoms, they usually cause severe side effects. Traditionally used Ayurvedic medicinal plants are a promising alternative for the management of arthritic symptoms, as they are safe and effective. Ayurvedic medicinal plants improve arthritic symptoms by reducing joint tenderness, joint pain, swelling, bone and cartilage damage, and increasing knee flexion, walking distance and sports activities. These beneficial effects of Ayurvedic medicinal plants on arthritis are mediated through various cellular mechanisms including inhibition of the inflammatory markers NF-κB, cytokines, adipokines, PGE2, NO, iNOS, COX-2, and MMPs and induction of antioxidant status by decreasing free radicals, lipid peroxidation, and myeloperoxidase, and increasing antioxidant enzymes, Nrf2, and HO-1. Thus, a strategy requires using these Ayurvedic medicinal plants to treat arthritis. This article describes the status of inflammation and oxidative stress in arthritic conditions. We also provide evidence that Ayurvedic medicinal plants and their bioactive components are highly effective in improving arthritic symptoms. | |
| 34803912 | A Network Biology Approach to Understanding the Tissue-Specific Roles of Non-Coding RNAs i | 2021 | Discovery of non-coding RNAs continues to provide new insights into some of the key molecular drivers of musculoskeletal diseases. Among these, microRNAs have received widespread attention for their roles in osteoarthritis and rheumatoid arthritis. With evidence to suggest that long non-coding RNAs and circular RNAs function as competing endogenous RNAs to sponge microRNAs, the net effect on gene expression in specific disease contexts can be elusive. Studies to date have focused on elucidating individual long non-coding-microRNA-gene target axes and circular RNA-microRNA-gene target axes, with a paucity of data integrating experimentally validated effects of non-coding RNAs. To address this gap, we curated recent studies reporting non-coding RNA axes in chondrocytes from human osteoarthritis and in fibroblast-like synoviocytes from human rheumatoid arthritis. Using an integrative computational biology approach, we then combined the findings into cell- and disease-specific networks for in-depth interpretation. We highlight some challenges to data integration, including non-existent naming conventions and out-of-date databases for non-coding RNAs, and some successes exemplified by the International Molecular Exchange Consortium for protein interactions. In this perspective article, we suggest that data integration is a useful in silico approach for creating non-coding RNA networks in arthritis and prioritizing interactions for further in vitro and in vivo experimentation in translational research. | |
| 34594326 | NKp30 Receptor Upregulation in Salivary Glands of Sjögren's Syndrome Characterizes Ectopi | 2021 | Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease resulting from the inflammatory infiltration of exocrine glands, mainly salivary and lacrimal glands, leading to secretory dysfunction and serious complications including debilitating fatigue, systemic autoimmunity, and lymphoma. Like other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, suggesting the involvement of innate immunity in pSS pathogenesis. NCR3/NKp30 is a natural killer (NK) cell-specific activating receptor regulating the cross talk between NK and dendritic cells including type II IFN secretion upon NK-cell activation. A genetic association between single-nucleotide polymorphisms (SNPs) in the NCR3/NKp30 promoter gene and a higher susceptibility for pSS has been previously described, with pSS patients most frequently carrying the major allele variant associated with a higher NKp30 transcript and IFN-γ release as a consequence of the receptor engagement. In the present study, we combined RNA-sequencing and histology from pSS salivary gland biopsies to better characterize NKp30 (NCR3) and its ligand B7/H6 (NCR3LG1) in pSS salivary gland tissues. Levels of NCR3/NKp30 were significantly increased both in salivary glands and in circulating NK cells of pSS patients compared with sicca controls, especially in salivary glands with organized ectopic lymphoid structures. In line with this observation, a strong correlation between NCR3/NKp30 levels and salivary gland infiltrating immune cells (CD3, CD20) was found. Furthermore, NCR3/NKp30 levels also correlated with higher IFN-γ, Perforin, and Granzyme-B expression in pSS SGs with organized ectopic lymphoid structures, suggesting an activation state of NK cells infiltrating SG tissue. Of note, NKp30+ NK cells accumulated at the border of the inflammatory foci, while the NKp30 ligand, B7/H6, is shown to be expressed mainly by ductal epithelial cells in pSS salivary glands. Finally, immunomodulatory treatment, such as the B-cell depleting agent rituximab, known to reduce the infiltration of immune cells in pSS SGs, prevented the upregulation of NCR3/NKp30 within the glands. | |
| 35102929 | Distal Renal Tubular Acidosis due to Primary Sjögren's Syndrome: Presents as Hypoakalemic | 2021 May | Classic distal renal tubular acidosis (dRTA) is characterized by inability to acidify the urine maximally (to | |
| 31335014 | Anatomy, Shoulder and Upper Limb, Hand Extensor Pollicis Longus Muscle. | 2022 Jan | An important contributor to thumb function, the extensor pollicis longus (EPL) muscle is an extrinsic thumb muscle which extends and adducts the thumb metacarpophalangeal (MCP) and interphalangeal (IP) joints. Innervated by the posterior interosseous nerve, the EPL receives its blood supply from the anterior interosseous artery, posterior interosseous artery, radial artery, and ulnar artery. Extensor pollicis longus variants are rare, with a prevalence of only 1%. The EPL tendon is associated with pathologies ranging from stenosing tenosynovitis to spontaneous tendon rupture. These pathologies are often seen in association with either medical comorbidities (e.g., rheumatoid arthritis) or as sequelae or associated pathology in the setting of trauma (e.g., distal radius fractures). In regards to the latter, the EPL may spontaneously rupture in up to 5% of adults following a nondisplaced distal radius fracture, or in pediatric patients who had dorsal plating for a displaced distal radius fracture. Overall, it is important to have a good understanding of the EPL to understand the anatomy and potential pathologies, particularly as each relates to the potential compromise of dynamic thumb function. |