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34221129 Body composition in patients with rheumatoid arthritis: a narrative literature review. 2021 There is growing interest in the alterations in body composition (BC) that accompany rheumatoid arthritis (RA). The purpose of this review is to (i) investigate how BC is currently measured in RA patients, (ii) describe alterations in body composition in RA patients and (iii) evaluate the effect on nutrition, physical training, and treatments; that is, corticosteroids and biologic Disease Modifying Anti-Rheumatic Disease (bDMARDs), on BC in RA patients. The primary-source literature for this review was acquired using PubMed, Scopus and Cochrane database searches for articles published up to March 2021. The Medical Subject Headings (MeSH) terms used were 'Arthritis, Rheumatoid', 'body composition', 'sarcopenia', 'obesity', 'cachexia', 'Absorptiometry, Photon' and 'Electric Impedance'. The titles and abstracts of all articles were reviewed for relevant subjects. Whole-BC measurements were usually performed using dual energy x-ray absorptiometry (DXA) to quantify lean- and fat-mass parameters. In RA patients, lean mass is lower and adiposity is higher than in healthy controls, both in men and women. The prevalence of abnormal BC conditions such as overfat, sarcopenia and sarcopenic obesity is significantly higher in RA patients than in healthy controls; these alterations in BC are observed even at an early stage of the disease. Data on the effect treatments on BC in RA patients are scarce. In the few studies published, (a) creatine supplementation and progressive resistance training induce a slight and temporary increase in lean mass, (b) exposure to corticosteroids induces a gain in fat mass and (c) tumour necrosis factor alpha (TNFα) inhibitors might be associated with a gain in fat mass, while tocilizumab might be associated with a gain in lean mass. The available data clearly demonstrate that alterations in BC occur in RA patients, but data on the effect of treatments, especially bDMARDs, are inconsistent and further studies are needed in this area.
33732715 Systemic Bone Density at Disease Onset Is Associated With Joint Erosion Progression in Ear 2021 Objectives: Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression. Methods: One-hundred twenty-eight patients with early rheumatoid arthritis (ERA) were recruited at disease onset. At study entry, demographic, clinical, and immunological parameters were recorded. Each ERA patient underwent plain X-rays of the hands and feet at study entry and after 12 months to assess the presence of erosions. After enrollment, each patient was treated according to the recommendations for RA management and followed up based on a treat-to-target (T2T) strategy. At baseline, blood samples for soluble biomarkers were collected from each patient, and plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), Dickkopf-1 (DKK1), and interleukin 6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Seventy-one ERA patients underwent bone mineral density (BMD) measurement at the left femoral neck and second to fourth lumbar spine vertebrae (L2-L4) by dual-energy X-ray absorptiometry (DXA). Results: Among the whole cohort, 34 (26.6%) ERA patients with bone erosions at study entry had a higher disease activity (p = 0.02) and IL-6 plasma levels (p = 0.03) than non-erosive ones. Moreover, at DXA, 33 (46.5%) ERA patients had osteopenia, and 16 (22.5%) had osteoporosis; patients with baseline bone erosions were more likely osteopenic/osteoporotic than non-erosive ones (p = 0.03), regardless of OPG, RANKL, and DKK1 plasma levels. Obese ERA patients were less likely osteopenic/osteoporotic than normal weight ones (p = 0.002), whereas anti-citrullinated protein antibodies (ACPA) positive ERA patients were more likely osteopenic/osteoporotic than ACPA negative ones (p = 0.034). At logistic regression analysis, baseline Disease Activity Score measured on 44 joints (DAS44) [OR: 2.46 (1.11-5.44)] and osteopenic/osteoporosis status [OR: 7.13 (1.27-39.94)] arose as independent factors of erosiveness. Baseline osteopenic/osteoporotic status and ACPA positivity were associated with bone damage progression during the follow-up. Conclusions: Bone erosions presence is associated with systemic bone loss since the earliest phases of RA, suggesting that the inflammatory burden and autoimmune biology, underpinning RA, represent crucial enhancers of bone remodeling either locally as at systemic level.
33593401 Prevalence and significance of serum 14-3-3η in juvenile idiopathic arthritis. 2021 Feb 16 BACKGROUND: Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14-3-3η in different types of JIA. METHODS: JIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children's Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14-3-3η were measured for all patients. 14-3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). RESULTS: Elevated 14-3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14-3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14-3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14-3-3η. The highest prevalence of 14-3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14-3-3η was not significantly associated with disease activity or age at diagnosis. CONCLUSION: Serum 14-3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14-3-3η does not appear to correlate with disease activity in JIA.
32942924 Arthropathy in hereditary haemochromatosis segregates with elevated erythrocyte mean corpu 2021 Mar Objective: To evaluate the relationship between erythrocyte parameters and the presence or absence of arthritis in HFE C282Y homozygous hereditary haemochromatosis (HH) subjects compared to control groups of non-HH subjects with arthritis.Method: Erythrocyte and arthritis parameters [mean corpuscular volume (MCV) and mean cell haemoglobin (MCH)] were obtained from consecutive HH subjects (n = 119) who were referred for initial evaluation and management. For comparison, MCV and MCH values were collected from randomly selected non-HH subjects with rheumatoid arthritis (n = 100) and osteoarthritis (n = 100), consisting of equal numbers of men and women. Two other comparison groups comprised 16 men and women who were heterozygous for C282Y with arthritis, and 38 non-HH subjects with type 2 polyarticular osteoarthritis (T2POA).Results: MCV values were significantly higher in HH subjects with arthritis (95 ± 0.56 fL) than in HH subjects without arthritis (92.75 ± 0.50 fL, p = 0.037). HH subjects with or without arthritis demonstrated a higher mean MCV than the control groups of non-HH osteoarthritis (90.12 ± 0.46 fL, p < 0.001) and non-HH rheumatoid arthritis (90.94 ± 0.57 fL, p < 0.001). HH subjects with arthritis also demonstrated a higher MCV than heterozygous C282Y subjects with arthritis (93.18 ± 1.55 fL, p = 0.025) and non-HH subjects with a similar pattern of arthritis, notably T2POA (91.13 ± 0.50 fL, p < 0.01). An MCV of ≥ 97.85 fL provided a likelihood ratio of 2.2 for development of arthritis in HH subjects.Conclusion: This study demonstrated a relationship between elevated MCV and arthritis in incident cases of HH.
34108876 Single Cell RNA-Seq Analysis Identifies Differentially Expressed Genes of Treg Cell in Ear 2021 Objective: Early treatment-naïve rheumatoid arthritis (RA) has defective regulatory T (Treg) cells and increased inflammation response. In this study, we aim to illustrate the regulation of Treg cells in pathogenesis of early rheumatoid arthritis by arsenic trioxide (As(2)O(3)). Methods: We studied the effects of As(2)O(3) on gene expression in early treatment-naïve RA Treg cells with single cell RNA-seq (scRNA-seq). Treg cells were sorted from peripheral blood mononuclear cells (PBMCs) and purified by fluorescence-activated cell sorting (FACS) and cultured with or without As(2)O(3) (at 0.1 µM) for 24 h. Total RNA was isolated and sequenced, and functional analysis was performed against the Gene Ontology (GO) database. Results for selected genes were confirmed with RT-qPCR. Results: As(2)O(3) exerts no significant effect on CD4(+) T-cell apoptosis under physical condition, and selectively modulate (CD4+) T cells toward Treg cells not Th17 cells under special polarizing stimulators. As(2)O(3) increased the expression of 200 and reduced that of 272 genes with fold change (FC) 2.0 or greater. Several genes associated with inflammation, Treg-cell activation and differentiation as well as glucose and amino acids metabolism were among the most strongly affected genes. GO function analysis identified top ten ranked significant biological process (BPs), molecular functions (MFs), and cell components (CCs) in treatment and nontreatment Treg cells. In GO analysis, genes involved in the immunoregulation, cell apoptosis and cycle, inflammation, and cellular metabolism were enriched among the significantly affected genes. The KEGG pathway enrichment analysis identified the forkhead box O (FoxO) signal pathway, apoptosis, cytokine-cytokine receptor interaction, cell cycle, nuclear factor-kappa B (NF-κB) signaling pathway, tumor necrosis factor α (TNF-α), p53 signaling pathway, and phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway were involved in the pathogenesis of early treatment-naïve RA. Conclusion: This is the first study investigating the genome-wide effects of As(2)O(3) on the gene expression of treatment-naïve Treg cells. In addition to clear anti-inflammatory and immunoregulation effects, As(2)O(3) affect amino acids and glucose metabolism in Treg cells, an observation that might be particularly important in the metabolic phenotype of treatment-naïve RA.
33995604 Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T 2021 BACKGROUND: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4(+)T subsets and the clinical feasibility of IL-2 therapies in patients with RA. METHODS: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment. RESULTS: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs (p < 0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4(+)T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values (p < 0.001), with no apparent side effects. CONCLUSION: Decreased absolute counts of circulating CD4(+)T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects. PLAIN LANGUAGE SUMMARY: Low-dose IL-2 treatment for rheumatoid arthritis • Circulating Tregs may be involved in the pathogenesis and progression of RA.• The absolute count of Tregs was significantly correlated with disease activity measures.• Low-dose IL-2 was able to effectively expade Tregs and help for RA patients' symptoms remission without evaluated side effects.
33753325 Circulating blood metabolite trajectories and risk of rheumatoid arthritis among military 2021 Mar 22 OBJECTIVES: We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis. METHODS: In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05. RESULTS: 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7±1.6 years; 1.0±0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (±8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking. CONCLUSIONS: In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis.
34441847 Infectious Pneumonia and Lower Airway Microorganisms in Patients with Rheumatoid Arthritis 2021 Aug 12 The relationship between microorganisms present in the lower respiratory tract and the subsequent incidence of pneumonia in patients with rheumatoid arthritis is unclear. A retrospective cohort study was designed to include a total of 121 patients with rheumatoid arthritis who underwent bronchoscopy at three hospitals between January 2008 and December 2017. Data on patient characteristics, microorganisms detected by bronchoscopy, and subsequent incidences of pneumonia were obtained from electronic medical records. Patients were divided into groups based on the microorganisms isolated from the lower respiratory tract. The cumulative incidence of pneumonia was assessed using the Kaplan-Meier method, and decision tree analysis was performed to analyze the relation between the presence of microorganisms and the occurrence of pneumonia. The most frequently isolated microbes were Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. Patients whose samples tested negative for bacteria or positive for normal oral flora were included in the control group. The rate of the subsequent incidence of pneumonia was higher in the P. aeruginosa group than in the control group (p = 0.026), and decision tree analysis suggested that P. aeruginosa and patient performance status were two important factors for predicting the incidence of pneumonia. In patients with rheumatoid arthritis, the presence of P. aeruginosa in the lower respiratory tract was associated with the subsequent incidence of pneumonia.
34275488 BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE s 2021 Jul 19 BACKGROUND: Our knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease relapses (flares), converting diseases from inactive to active states. Focussing on rheumatoid arthritis (RA), the challenge that we will address is why IMIDs remit and relapse. Extrapolating from pathogenetic factors involved in disease initiation, new episodes of inflammation could be triggered by recurrent systemic immune dysregulation or locally by factors within the joint, either of which could be endorsed by overarching epigenetic factors or changes in systemic or localised metabolism. METHODS: The BIO-FLARE study is a non-randomised longitudinal cohort study that aims to enrol 150 patients with RA in remission on a stable dose of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), who consent to discontinue treatment. Participants stop their DMARDs at time 0 and are offered an optional ultrasound-guided synovial biopsy. They are studied intensively, with blood sampling and clinical evaluation at weeks 0, 2, 5, 8, 12 and 24. It is anticipated that 50% of participants will have a disease flare, whilst 50% remain in drug-free remission for the study duration (24 weeks). Flaring participants undergo an ultrasound-guided synovial biopsy before reinstatement of previous treatment. Blood samples will be used to investigate immune cell subsets, their activation status and their cytokine profile, autoantibody profiles and epigenetic profiles. Synovial biopsies will be examined to profile cell lineages and subtypes present at flare. Blood, urine and synovium will be examined to determine metabolic profiles. Taking into account all generated data, multivariate statistical techniques will be employed to develop a model to predict impending flare in RA, highlighting therapeutic pathways and informative biomarkers. Despite initial recruitment to time and target, the SARS-CoV-2 pandemic has impacted significantly, and a decision was taken to close recruitment at 118 participants with complete data. DISCUSSION: This study aims to investigate the pathogenesis of flare in rheumatoid arthritis, which is a significant knowledge gap in our understanding, addressing a major unmet patient need. TRIAL REGISTRATION: The study was retrospectively registered on 27/06/2019 in the ISRCTN registry 16371380 .
34148193 A Molecular Signature Response Classifier to Predict Inadequate Response to Tumor Necrosis 2021 Sep INTRODUCTION: Timely matching of patients to beneficial targeted therapy is an unmet need in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) that predicts which patients with RA are unlikely to respond to tumor necrosis factor-α inhibitor (TNFi) therapy would have wide clinical utility. METHODS: The protein-protein interaction map specific to the rheumatoid arthritis pathophysiology and gene expression data in blood patient samples was used to discover a molecular signature of non-response to TNFi therapy. Inadequate response predictions were validated in blood samples from the CERTAIN cohort and a multicenter blinded prospective observational clinical study (NETWORK-004) among 391 targeted therapy-naïve and 113 TNFi-exposed patient samples. The primary endpoint evaluated the ability of the MSRC to identify patients who inadequately responded to TNFi therapy at 6 months according to ACR50. Additional endpoints evaluated the prediction of inadequate response at 3 and 6 months by ACR70, DAS28-CRP, and CDAI. RESULTS: The 23-feature molecular signature considers pathways upstream and downstream of TNFα involvement in RA pathophysiology. Predictive performance was consistent between the CERTAIN cohort and NETWORK-004 study. The NETWORK-004 study met primary and secondary endpoints. A molecular signature of non-response was detected in 45% of targeted therapy-naïve patients. The MSRC had an area under the curve (AUC) of 0.64 and patients were unlikely to adequately respond to TNFi therapy according to ACR50 at 6 months with an odds ratio of 4.1 (95% confidence interval 2.0-8.3, p value 0.0001). Odds ratios (3.4-8.8) were significant (p value < 0.01) for additional endpoints at 3 and 6 months, with AUC values up to 0.74. Among TNFi-exposed patients, the MSRC had an AUC of up to 0.83 and was associated with significant odds ratios of 3.3-26.6 by ACR, DAS28-CRP, and CDAI metrics. CONCLUSION: The MSRC stratifies patients according to likelihood of inadequate response to TNFi therapy and provides patient-specific data to guide therapy choice in RA for targeted therapy-naïve and TNFi-exposed patients.
34831223 Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis. 2021 Nov 3 Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.
34093745 Limiting factors to Boolean remission differ between autoantibody-positive and -negative p 2021 BACKGROUND: The patient global assessment of disease activity (PGA) is the major limiting factor to Boolean remission in patients with established rheumatoid arthritis (RA). Here, we investigated the limiting variables to disease remission in patients with early RA treated with conventional synthetic disease modifying anti-rheumatic drugs, also in relation to autoantibody status. METHODS: Data were retrieved from 535 early RA patients (<12 months of symptoms) with an observation period of 6-12 months upon initiation of therapy with methotrexate aimed at the achievement of low disease activity based on the 28-joints disease activity score. Near-remission was defined as any of the four core items of Boolean remission >1 with the remaining three all ⩽1. Reasons for missing Boolean remission and predictors of near-remission subcategories were analyzed in relation to baseline disease variables. RESULTS: After 6 and 12 months, near-remission was two-times more frequent than Boolean remission (25.6% and 26.9% at the two time-points). A 28-swollen joint count (SJC28) >1 was responsible for the majority of near-remission (56.2% and 57.6% at 6 and 12 months, respectively), and PGA > 1 accounted for approximatively 35% of the cases. Autoantibody-positivity independently predicted the risk of missing remission because of SJC28 > 1 [adjusted odds ratio (OR) 95% confidence interval (CI) 2.81 (1.59-4.9) at 6 months and 1.73 (1.01-3.01) at 12 months], whilst autoantibody-negativity was an independent predictor of PGA near-remission [adjusted OR (95% CI) 2.45 (1.25-4.80) at 6 months and 5.71 (2.47-13.2) at 12 months]. CONCLUSION: In early RA, Boolean remission is more frequently missed because of persistent swollen joints. However, barriers to full-remission vary in relation to the autoantibody status. Autoantibody-positive patients more commonly experience residual swollen joints, whilst PGA more frequently impairs remission in autoantibody-negative patients. Efforts to target full-remission in early RA may thus require different strategies according to autoantibody profile.
32766690 Neutrophil-derived lipocalin-2 in adult-onset Still's disease: a novel biomarker of diseas 2021 Jan 5 OBJECTIVE: Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. METHODS: Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. RESULTS: LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. CONCLUSION: Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation.
32666850 Collision Lesions of Calcifying Pseudoneoplasm of the Neuraxis and Rheumatoid Nodules: A C 2021 May Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unclear pathogenesis. Collision lesions of CAPNONs with neoplasms are occasionally reported. In this article, we report the first case of collision lesions between CAPNON and rheumatoid nodules (RNs) in a patient with systemic lupus erythematosus. The patient was a 51-year-old female who presented with lower back pain and subsequently a lower back mass over 2 years. Spinal magnetic resonance imaging demonstrated a heterogeneous, partially calcified mass centered in the L3-4 paravertebral regions. A biopsy of the mass was diagnostic of CAPNON. As the mass grew over the following 5 months, it was resected en bloc. Its pathological examination revealed collision lesions of RNs at different histopathological stages and CAPNON lesions, and transitional lesions exhibiting combined RN and CAPNON features, with immune cell infiltrates. Our findings provide new evidence for an immune-mediated reactive process and insights into the pathogenies of CAPNON.
34884709 Salivary Biomarkers in Patients with Sjögren's Syndrome-A Systematic Review. 2021 Nov 29 Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy and non-invasive. Since 1900, salivary proteomic analysis has been performed continuously using a variety of optimized analytical methods. Many studies have identified distinct characteristics of salivary proteins in patients with primary SS, and the changes were related to chronic inflammation and overproduction of immunoglobulins or downregulated secretory function. Several proteomic studies using whole or parotid saliva have evaluated whether several salivary proteins can be used to discriminate SS, including salivary β2-microglobulin, calprotectin, carbonic anhydrase VI, neutrophil gelatinase-associated lipocalin, sialic acid-binding immunoglobulin-like lectin-5, and tripartite motif-containing protein 29. In addition, salivary proinflammatory cytokine levels have been reported to be increased in patients with SS. Although these candidate salivary proteins have exhibited considerable differences in patients with SS, more data are needed to confirm their role as biomarkers. Moreover, the identification of salivary characteristics that can accurately reflect disease activity, predict treatment response and prognosis, and diagnose SS is anticipated.
33191176 Long noncoding RNA ZFAS1 silencing alleviates rheumatoid arthritis via blocking miR-296-5p 2021 Jan Rheumatoid arthritis (RA), a chronic inflammatory disease, deprives patients' walking ability and reduces their life quality worldwide. Though recent studies have indicated the role of long noncoding RNA (lncRNA) ZFAS1 in several diseases, however, its role in RA remains uncharacterized. The present study aimed to unravel the the effect of ZFAS1 on RA. Herein, the RA mouse model and the human RA synoviocyte MH7A cell lines stimulated with TNF-α were established. ZFAS1 was next determined to be highly expressed in the mice with RA-like symptoms and TNF-α-stimulated MH7A cells while inhibiting ZFAS1 was demonstrated to promote proliferation and suppress apoptosis of MH7A cells. Furthermore, ZFAS1 knockdown exerted anti-inflammation effect in vitro and in vivo and reduced the arthritis index value. Moreover, RNA immunoprecipitation and dual-luciferase reporter assays identified the binding of ZFAS1 to microRNA (miR)-296-5p as well as the binding of miR-296-5p to matrix metalloproteinase-15 (MMP-15). Of note, ZFAS1 could bind miR-296-5p to up-regulate the expression of MMP-15. Our results from in vitro and in vivo experiments demonstrated silencing ZFAS1 mitigated RA-like symptoms such as inflammation and hyperplasia via miR-296-5p-dependent inhibition of MMP-15. Taken altogether, our study confirmed that ZFAS1 involved in RA progression by competitively binding to miR-296-5p and regulating MMP-15 expression.
34145316 Long-term clinical course and outcome in patients with primary Sjögren syndrome-associate 2021 Jun 18 Interstitial lung disease (ILD) is the most common lung manifestation in patients with Sjögren syndrome (SJS) and is associated with poor outcomes. This study aimed to investigate the long-term clinical course and prognostic factors in patients with SJS-ILD. Clinical data and high-resolution computed tomography (HRCT) images of 62 patients with primary SJS-ILD were retrospectively analyzed (biopsy-proven cases, n = 16). The mean patient age was 59.8 years; 83.9% of the patients were females, and 38.7% showed a usual interstitial pneumonia (UIP) pattern on HRCT. The median follow-up period was 61.5 months. During follow-up, 15 patients (24.2%) died, 7 (11.3%) experienced acute exacerbation (AE), and 27 (43.5%) progressed. The 1-, 3- and 5-year survival rates were 93.5%, 85.8%, and 81.1%, respectively. Age (hazard ratio [HR]: 1.158, P = 0.003), C-reactive protein (CRP) level (HR: 1.212, P = 0.045), FVC (HR: 0.902, P = 0.005), and a UIP pattern on HRCT (HR: 4.580, P = 0.029) were significant prognostic factors in multivariable Cox analysis. In conclusion, death, AE, and ILD progression occurred in 25%, 10%, and 50% of the patients with SJS-ILD, respectively. Older age, higher CRP level, lower FVC, and a UIP pattern on HRCT indicated poor prognosis.
33310686 Early diagnosis and treatment for Sjögren's syndrome: current challenges, redefined disea 2021 Feb There are some challenges and unmet needs in the early diagnosis and management of Sjögren's syndrome (SjS) such as prominent glandular dysfunction at diagnosis and long diagnostic delay. Those challenges are partly attributed to the lack of a good knowledge of the early stages of SjS, which is a major obstacle to delivering appropriate care to SjS patients. Findings from both clinical and experimental studies suggest the plausibility of a redefined SjS course consisting of 4 stages, which includes initiation stage, preclinical stage, asymptomatic SjS stage and overt SjS stage. More studies focusing on the pathological processes and changes during the early stages of SjS are needed. To enable early diagnosis and treatment for SjS, more useful biomarkers of the early stages of SjS need to be identified, and individuals at high risk of SjS development need to be identified. Appropriate screening can be performed to facilitate the early diagnosis of SjS among those high-risk individuals.
33147609 Burden of illness among subgroups of patients with primary Sjögren's syndrome and systemi 2021 Apr 6 OBJECTIVES: To describe how patients with primary SS (pSS) and systemic organ involvement are classified and clustered in routine practice. METHODS: This multinational, cross-sectional survey of real-world quantitative data was conducted across Europe and the US. Rheumatologists who treated seven or more adult patients per month with pSS and current/past systemic manifestations undertook a survey before completing a patient record form capturing demographic, clinical and treatment information for their next six eligible patients. Patients with a completed patient record form were invited to complete a patient self-completion questionnaire capturing insights into their disease and treatment. Subgroups were defined by physicians' assessment of disease severity; clusters were derived based on key clinical characteristics using latent class analysis. RESULTS: Rheumatologists completed 316 physician surveys and 1879 patient record forms; 888 patients completed the patient self-completion questionnaire. pSS severity reflected organ involvement and symptomatology. Latent class analysis produced five clusters distinguished by the organ systems involved and the presence of pain and fatigue symptoms at the time of the survey. A minority of patients [n = 67 (4%)] were categorized with multiple organ involvement and the highest frequency of pain and fatigue. A total of 324 patients (17%) were categorized as 'low burden'. The remaining three clusters exhibited high frequencies of articular involvement but were distinguished by the extent of other organ system involvement. CONCLUSION: Cluster analysis using a real-world cohort of patients with pSS and systemic organ involvement highlights the heterogeneous presentation of patients with pSS and confirms the importance of pain and fatigue as well as organ involvement when determining disease burden.
34387735 Cardiac involvement in primary SjÓ§gren's syndrome. 2022 Feb Primary SjÓ§gren's syndrome (pSS) is an autoimmune-mediated, inflammatory, and systemic connective tissue disease (CTD), especially in middle-aged women, which often involves multiple systems and organs of the body. In fact, the heart is an important target organ in patients with pSS. In recent years, it has been confirmed that the morbidity of cardiac involvement has increased in patients with pSS, and cardiovascular disease (CVD) is one of the main causes of death. The increased risk of CVD in pSS patients is associated with a great variety of risk factors, such as age, gender, hypertension, diabetes mellitus, dyslipidemia, disease duration, extra-glandular manifestations, therapeutic drugs of pSS, and so on. Early recognition and effective treatment of CVD may play a crucial role in improving adverse cardiovascular prognosis. Whereas cardiac involvement is closely related to patient prognosis and survival, the cardiac involvement of patients with pSS remains poorly studied. Therefore, this article reviews the cardiovascular risk factors, clinical manifestations of cardiac involvement, cardiovascular biomarkers, and therapeutic strategies of pSS patients.