Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30336792 Angiogenic T cells in primary Sjögren's syndrome: a double-edged sword? 2019 May OBJECTIVES: The mechanisms underlying increased cardiovascular risk in primary Sjögren's syndrome (pSS) remain unclear. Since the recently discovered angiogenic T cells (Tang) may participate in endothelial repair by cooperating with endothelial progenitor cells (EPC), we aimed to quantify and characterise Tang in the peripheral blood and minor salivary glands (MSG) of pSS patients. METHODS: Tang (CD3+CD31+CXCR4+) and EPC (CD34+CD133+VEGFR-2+) were quantified by flow cytometry in peripheral blood samples from 36 pSS patients and 20 healthy donors. Tang subsets were assessed on the basis of CD4, CD8 and CD28 expression. Labial MSG sections from 10 pSS patients and 12 non-pSS sicca syndrome controls were subjected to immunofluorescence staining to investigate the presence of Tang and the expression of the CXCR4-ligand stromal cell-derived factor-1 (SDF-1)/CXCL12. RESULTS: Circulating Tang cells were expanded and directly correlated to EPC in pSS. Both Tang and EPC directly correlated with disease activity as calculated with the EULAR Sjögren's syndrome disease activity index (ESSDAI). In pSS, the majority of Tang cells were CD4-CD8- double negative (DN) and lacked CD28 revealing a senescent phenotype. A subset of CD4+, CD8+ and DN Tang cells produced interleukin-17. Immunohistology revealed the exclusive presence of periductal and perivascular infiltrating Tang cells along with increased SDF-1/CXCL12 expression in pSS MSG compared to non-pSS sicca syndrome controls. CONCLUSIONS: In pSS, Tang cells are expanded in peripheral blood and infiltrate MSG. Tang may be novel actors in pSS-related endothelial dysfunction and glandular neo-angiogenesis and inflammation.
31657702 Interstitial lung abnormalities in patients with early rheumatoid arthritis: A pilot study 2019 Oct OBJECTIVE: Pulmonary disease is a leading cause of morbidity and mortality in rheumatoid arthritis (RA). In this study, we investigated the prevalence and progression of interstitial lung abnormalities (ILA) in a prospective cohort study of 18 subjects with early RA. METHODS: Eighteen adults diagnosed with anti-citrullinated protein-antibody-positive RA within the prior year underwent baseline high-resolution computed tomography (HRCT), symptom assessment, and pulmonary function and laboratory testing. The follow-up HRCT and clinical assessment were completed after 1 year. RESULTS: Seven of the 18 patients (39%) had baseline HRCT abnormalities including septal thickening, honeycombing, ground glass opacities, and/or traction bronchiectasis. At follow-up, 6 out of the 7 subjects (86%) with ILAs at baseline exhibited progression, while 10 out of 11 (91%) without ILAs at baseline remained stable. A higher Clinical Chronic Obstructive Pulmonary Disease Questionnaire score was associated with both the presence and progression of HRCT abnormalities (10 vs 2, p=0.045; 10 vs 2, p=0.009, respectively). C-reactive protein (CRP) trended higher in patients with radiologic abnormalities (3.5 mg/L vs 1.1 mg/L, p=0.08) and was significantly higher in those with progression (3.5 mg/L vs 1 mg/L, p=0.024). Smoking, pulmonary function, and autoantibodies were not associated with HRCT abnormalities. CONCLUSION: ILAs are prevalent in patients with early RA. If identified at baseline, radiographic progression of ILAs after 1 year is likely, while those without ILAs at baseline are unlikely to develop new ILAs. In addition, early respiratory symptoms and higher CRP levels may correlate with the presence and progression of underlying ILAs.
31213547 Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local p 2019 Jul 2 Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.
31872183 The Impact of Exercise, Lifestyle, and Clinical Factors on Perceived Cognitive Function in 2019 Dec OBJECTIVE: Lifestyle factors, such as inactivity and obesity, contribute to cognitive decline in the general population, but little is known about how these factors may affect individuals with a chronic inflammatory condition such as rheumatoid arthritis (RA). We studied the clinical and functional risk factors related to a worsening of perceived cognitive function in patients with RA. METHODS: We collected clinical and functional questionnaire data over 10 years in a prospective RA cohort including yearly self-reported memory, concentration, and word-finding difficulties graded from "never" to "often." Generalized estimating equation models examined the role of exercise (defined as those meeting the Department of Health and Human Services physical activity guidelines of 75 minutes of vigorous or 150 minutes of moderate aerobic activity per week), body mass index (BMI), sleep, depression (Mental Health Index-Depression), Disease Activity Score (DAS)28-c-reactive protein (CRP)3 score, disease-modifying antirheumatic drug, and corticosteroid use from the previous year as predictors of cognitive complaints that progressed to "often" compared with the previous year (the first year (T (i) ) progressed to "often" 1 year later (T (i+1))). RESULTS: Of 1219 RA subjects, 127 (10.4%) described either poor memory, concentration, or word-finding difficulties as affecting them "often" at study entry. RA patients (n = 1092, mean age = 56.5 years, 82% female, 58% college educated) were less likely to report word-finding difficulties, poor memory, and concentration as "often" if they were physically active (p = 0.0001, P = 0.01, P < 0.0001, respectively). Female RA patients developed more concentration complaints compared with males (P = 0.03); patients taking an anti-tumor necrosis factor therapy were less likely to complain of poor memory (P = 0.01). Sleep, BMI, fatigue, depression, DAS28-CRP3, methotrexate, and corticosteroid use were not independently associated with a worsening of any cognitive complaints. CONCLUSION: RA patients who are physically active are less likely to report cognitive difficulties. Our study suggests potential modifiable risk factors for the prevention of cognitive dysfunction in RA.
31440254 Epigenome-Wide Comparative Study Reveals Key Differences Between Mixed Connective Tissue D 2019 Mixed Connective Tissue Disease (MCTD) is a rare complex systemic autoimmune disease (SAD) characterized by the presence of increased levels of anti-U1 ribonucleoprotein autoantibodies and signs and symptoms that resemble other SADs such as systemic sclerosis (SSc), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Due to its low prevalence, this disease has been very poorly studied at the molecular level. We performed for the first time an epigenome-wide association study interrogating DNA methylation data obtained with the Infinium MethylationEPIC array from whole blood samples in 31 patients diagnosed with MCTD and 255 healthy subjects. We observed a pervasive hypomethylation involving 170 genes enriched for immune-related function such as those involved in type I interferon signaling pathways or in negative regulation of viral genome replication. We mostly identified epigenetic signals at genes previously implicated in other SADs, for example MX1, PARP9, DDX60, or IFI44L, for which we also observed that MCTD patients exhibit higher DNA methylation variability compared with controls, suggesting that these sites might be involved in plastic immune responses that are relevant to the disease. Through methylation quantitative trait locus (meQTL) analysis we identified widespread local genetic effects influencing DNA methylation variability at MCTD-associated sites. Interestingly, for IRF7, IFI44 genes, and the HLA region we have evidence that they could be exerting a genetic risk on MCTD mediated through DNA methylation changes. Comparison of MCTD-associated epigenome with patients diagnosed with SLE, or Sjögren's Syndrome, reveals a common interferon-related epigenetic signature, however we find substantial epigenetic differences when compared with patients diagnosed with rheumatoid arthritis and systemic sclerosis. Furthermore, we show that MCTD-associated CpGs are potential epigenetic biomarkers with high diagnostic value. Our study serves to reveal new genes and pathways involved in MCTD, to illustrate the important role of epigenetic modifications in MCTD pathology, in mediating the interaction between different genetic and environmental MCTD risk factors, and as potential biomarkers of SADs.
31221169 An online experiment to assess bias in professional medical coding. 2019 Jun 20 BACKGROUND: Multiple studies have documented bias in medical decision making, but no studies have examined whether this bias extends to medical coding practices. Medical coding is foundational to the US health care enterprise. We evaluate whether bias based on patient characteristics influences specific coding practices of professional medical coders. METHODS: This is an online experimental study of members of a national professional medical coding organization. Participants were randomly assigned a set of six clinical scenarios reflecting common medical conditions and asked to report encounter level of service codes for these clinical scenarios. Clinical scenarios differed by patient demographics (race, age, gender, ability) or social context (food insecurity, housing security) but were otherwise identical. We estimated Ordinary Least Squares regression models to evaluate differences in outcome average visit level of service by patient demographic characteristics described in the clinical scenarios; we adjusted for coders' age, gender, race, and years of coding experience. RESULTS: The final analytic sample included 586 respondents who coded at least one clinical scenario. Higher mean level of service was assigned to clinical scenarios describing seniors compared to middle-aged patients in two otherwise identical scenarios, one a patient with type II diabetes mellitus (Coef: 0.28, SE: 0.15) and the other with rheumatoid arthritis (Coef: 0.30, SE: 0.13). Charts describing women were assigned lower level of service than men in patients with asthma exacerbation (Coef: -0.25, SE: 0.13) and rheumatoid arthritis (Coef: -0.20, SE: 0.12). There were no other significant differences in mean complexity score by patient demographics or social needs. CONCLUSION: We found limited evidence of bias in professional medical coding practice by patient age and gender, though findings were inconsistent across medical conditions. Low levels of observed bias may reflect medical coding workflow and training practices. Future research is needed to better understand bias in coding and to identify effective and generalizable bias prevention practices.
32096930 Pulmonary Manifestations of Systemic Diseases. 2019 Systemic diseases are characterized by typical manifestations in more than one organ system. The most common systemic diseases to affect the lungs include sarcoidosis, connective tissue disease, and vasculitis. Imaging, and in particular computed tomography, plays a key role in several respects including (1) formulating a diagnosis, (2) determining the pattern of injury present, and (3) the serial evaluation of patients with progressive or acute symptoms. The goal of this chapter is to describe the typical imaging features of systemic diseases that involve the lungs and to delineate the role of imaging in the multidisciplinary diagnosis of systemic disorders.
31621563 Knee and hip osteoarthritis as predictors of premature death: a review of the evidence. 2019 Sep Rheumatic and musculoskeletal diseases (RMDs) are common, with osteoarthritis (OA) being the most prevalent. RMDs, including OA, are associated with significant pain and functional limitations, as well as mortality rates up to 1.6-fold higher than in the general population. Most studies of OA and mortality have focused on knee and hip OA. Some, but not all, of these studies suggest an increased risk of death, however risks may differ by region. Reasons for discordant findings may be due to methodological considerations including definition of OA, study design, length of follow-up, and whether variables that can change and develop over time, such as measures of OA, body mass index (BMI) and comorbidities, were re-assessed during the follow-up period. Research has shown that the prognosis of OA is similar to that seen in rheumatoid arthritis (RA) patients, in many respects. In RA, disability and comorbidities are the most important predictors of mortality, although pain may be more prominent in the prognosis of OA mortality. The data suggest that addressing functional limitations and pain seen with OA could potentially reduce the increased mortality that has been observed in these individuals. Further study is needed concerning the potential excess mortality attributable to lower body OA, as well as associated disability, pain and comorbidities.
31114679 Contribution of pulmonary function tests (PFTs) to the diagnosis and follow up of connecti 2019 INTRODUCTION: Connective Tissue Diseases (CTDs) are systemic autoimmune conditions characterized by frequent lung involvement. This usually takes the form of Interstitial Lung Disease (ILD), but Obstructive Lung Disease (OLD) and Pulmonary Artery Hypertension (PAH) can also occur. Lung involvement is often severe, representing the first cause of death in CTD. The aim of this study is to highlight the role of Pulmonary Function Tests (PFTs) in the diagnosis and follow up of CTD patients. MAIN BODY: Rheumatoid Arthritis (RA) showed mainly an ILD with a Usual Interstitial Pneumonia (UIP) pattern in High-Resolution Chest Tomography (HRCT). PFTs are able to highlight a RA-ILD before its clinical onset and to drive follow up of patients with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DL(CO)). In the course of Scleroderma Spectrum Disorders (SSDs) and Idiopathic Inflammatory Myopathies (IIMs), DL(CO) appears to be more sensitive than FVC in highlighting an ILD, but it can be compromised by the presence of PAH. A restrictive respiratory pattern can be present in IIMs and Systemic Lupus Erythematosus due to the inflammatory involvement of respiratory muscles, the presence of fatigue or diaphragm distress. CONCLUSIONS: The lung should be carefully studied during CTDs. PFTs can represent an important prognostic tool for diagnosis and follow up of RA-ILD, but, on their own, lack sufficient specificity or sensitivity to describe lung involvement in SSDs and IIMs. Several composite indexes potentially able to describe the evolution of lung damage and response to treatment in SSDs are under investigation. Considering the potential severity of these conditions, an HRCT jointly with PFTs should be performed in all new diagnoses of SSDs and IIMs. Moreover, follow up PFTs should be interpreted in the light of the risk factor for respiratory disease related to each disease.
31872182 Palindromic Rheumatism Frequently Precedes Early Rheumatoid Arthritis: Results From an Inc 2019 Dec BACKGROUND: This multicenter incident cohort aimed to characterize how often early rheumatoid arthritis (ERA) patients self-report episodic joint inflammation (palindromic rheumatism) preceding ERA diagnosis and which characteristics differentiate these patients from those without prior episodic symptoms. METHODS: Data were from patients with early confirmed or suspected RA (more than 6 weeks and less than 12 months) enrolled in the Canadian Early ArThritis CoHort (CATCH) between April 2017 to March 2018 who completed study case report forms assessing joint pain and swelling prior to ERA diagnosis. Chi-square and t tests were used to compare characteristics of patients with and without self-reported episodic joint inflammation prior to ERA diagnosis. Multivariable logistic regression was used to identify sociodemographic and clinical measures associated with past episodic joint inflammation around the time of ERA diagnosis. RESULTS: A total of 154 ERA patients were included; 66% were female, and mean (SD) age and RA symptom duration were 54 (15) years and 141 (118) days. Sixty-five (42%) ERA patients reported a history of episodic joint pain and swelling, half of whom reported that these symptoms preceded ERA diagnosis by over 6 months. ERA patients with past episodic joint inflammation were more often female, had higher income, were seropositive, had more comorbidities, fewer swollen joints, and lower Clinical Disease Activity Index (CDAI) around the time of ERA diagnosis (P < 0.05). These associations remained significant in multivariable regression adjusting for other sociodemographic and RA clinical measures. CONCLUSION: Almost half of ERA patients experienced episodic joint inflammation prior to ERA diagnosis. These patients were more often female, had higher income, and presented with milder disease activity at ERA diagnosis.
31882624 Experimental arthritis and Porphyromonas gingivalis administration synergistically decreas 2019 Dec 27 Porphyromonas gingivalis infection can lead to periodontitis and dysbiosis, which are known risk factors for rheumatoid arthritis (RA). We investigated whether P. gingivalis administration affected bone regeneration in mice with or without arthritis. We administered P. gingivalis to male DBA/1 J mice that were or were not sensitised to type II collagen-induced arthritis (CIA). All mice underwent drilling of bilateral femurs. We histologically evaluated new bone regeneration (bone volume of the defect [BVd]/tissue volume of the defect [TVd]) using micro-computed tomography (micro-CT), osteoclast number/bone area, and active osteoblast surface/bone surface (Ob.S/BS). We measured serum cytokine levels and bone mineral density of the proximal tibia using micro-CT. CIA resulted in significantly reduced bone regeneration (BVd/TVd) at all time-points, whereas P. gingivalis administration showed similar effects at 2 weeks postoperatively. CIA resulted in higher osteoclast number/bone area and lower Ob.S/BS at 2 and 3 weeks postoperatively, respectively. However, P. gingivalis administration resulted in lower Ob.S/BS only at 2 weeks postoperatively. During later-stage bone regeneration, CIA and P. gingivalis administration synergistically decreased BVd/TVd, increased serum tumour necrosis factor-α, and resulted in the lowest bone mineral density. Therefore, RA and dysbiosis could be risk factors for prolonged fracture healing.
31112005 Changes in Lipid Levels and Incidence of Cardiovascular Events Following Tofacitinib Treat 2019 Oct OBJECTIVE: The risk of cardiovascular disease (CVD) is higher in patients with psoriatic arthritis (PsA) compared to the general population. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Because tofacitinib increases circulating lipid levels in some patients, we evaluated CVD risk factors and major adverse cardiovascular events (MACE) in patients with active PsA receiving tofacitinib 5 or 10 mg twice daily plus conventional synthetic disease-modifying antirheumatic drugs. METHODS: Data were pooled from 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond]) and 1 ongoing long-term extension (Open-Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance], data cutoff January 2017; database not locked). Outcomes included fasting lipid levels, blood pressure, hypertension-related adverse events (AEs; including hypertension, high blood pressure, and increased blood pressure), and MACE. RESULTS: Overall, 783 tofacitinib-treated patients were included. Percentage increases from baseline in low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels ranged from 9% to 14% for tofacitinib 5 mg and 10 mg at 3 and 6 months; no meaningful changes in LDL-c:HDL-c or total cholesterol:HDL-c ratios were observed. Blood pressure remained stable for 24 months. Fifty-eight patients (7.4%) had hypertension-related AEs; none were fatal (incidence rate [IR] per 100 patient-years 4.81 [95% confidence interval (95% CI) 3.65-6.22]). Five patients (0.6%) had MACE (IR 0.24 [95% CI 0.05-0.70]); 2 were fatal. CONCLUSION: Serum lipid level increases at month 3 following tofacitinib treatment in PsA were consistent with observations in rheumatoid arthritis and psoriasis. The IR of hypertension-related AEs and MACE was low; long-term follow-up is ongoing.
31102126 Co-Nanoencapsulation of Vitamin D(3) and Curcumin Regulates Inflammation and Purine Metabo 2019 Oct We analyzed the effects of a nanoencapsulated association of curcumin and vitamin D(3) on purine metabolism enzymes in neutrophils, lymphocytes, and platelets in a model of adjuvant-induced arthritis (AIA) in rats. Following AIA induction, the animals were treated for 15 days with free and nanoencapsulated curcumin (4 mg/kg), nanocapsules of vitamin D(3) (VD3) (15.84 IU/day), a nanoencapsulated combination of curcumin and VD3, vehicle, or blank nanocapsules. The animals were euthanized, and blood was collected to evaluate the activities of E-NTPDase, adenosine deaminase (ADA), and myeloperoxidase (MPO), as well as reactive oxygen species (ROS) levels and biochemical parameters. Also, the liver and kidney were collected for histological analysis. The changes in the activities of purinergic enzymes indicated that inflammation was significantly reverted by vitamin D(3) and curcumin co-nanoencapsulation treatments in the arthritic rats. The reduction of inflammation was confirmed by the reduction in the signs and symptoms of AIA, as well as in MPO activity by all formulations. The treatments with nanocapsules reverted histological alterations in the kidney. Serum parameters were not altered by the induction or treatments. Our results suggest that co-nanoencapsulation of vitamin D(3) and curcumin is an efficient alternative adjuvant treatment for rheumatoid arthritis as it reverts the changes in the purine metabolism and reduces arthritis-associated inflammation.
30221487 Incidence, Clinical Manifestations, and Severity of Juvenile Idiopathic Arthritis Among Ma 2019 Sep OBJECTIVE: To describe the incidence, demographics, diagnostic clinical manifestations, and severity of juvenile idiopathic arthritis (JIA) in Maori and Pacific Island children compared to European children. METHODS: A chart review was conducted of all children with JIA seen by Auckland pediatric and rheumatology services between the years 2000 and 2015. Demographic data and diagnostic clinical manifestations, including poor prognostic features, were collated. The incidence, diagnostic, clinical manifestations, and severity of JIA were determined and compared between ethnic groups, in particular Maori, Pacific Island, and European children. RESULTS: The overall incidence in a New Zealand cohort of children with JIA was 5.1/100,000 children per year, which was significantly higher among European children (7.2/100,000 children per year) compared to all other ethnic groups. Poor prognostic features at diagnosis were present in 36% of children with JIA, with significantly more Maori and Pacific Island children presenting with poor prognostic features compared to European children (58% versus 27%; P = 0.0001). Maori and Pacific Island children had significantly more poor prognostic features per child associated with JIA (1.10 versus 0.37; P < 0.0001) and in oligoarticular and polyarticular JIA (1.28 versus 0.40; P < 0.0001), which was independent of socioeconomic status. Significant features included cervical involvement (25% versus 9%; P = 0.03), erosive changes (22% versus 8%; P = 0.05), joint space narrowing (13% versus 2%; P = 0.02), and positive rheumatoid factor polyarticular disease (47% versus 14%; P = 0.01). CONCLUSION: Maori and Pacific Island children were more likely to present with poor prognostic features at diagnosis, although the incidence of JIA was demonstrated to be significantly higher among European children compared to all ethnic groups.
31830591 Baseline self-report 'central mechanisms' trait predicts persistent knee pain in the Knee 2020 Feb OBJECTIVES: We investigated whether baseline scores for a self-report trait linked to central mechanisms predict 1 year pain outcomes in the Knee Pain in the Community cohort. METHOD: 1471 participants reported knee pain at baseline and responded to a 1-year follow-up questionnaire, of whom 204 underwent pressure pain detection thresholds (PPTs) and radiographic assessment at baseline. Logistic and linear regression models estimated the relative risks (RRs) and associations (β) between self-report traits, PPTs and pain outcomes. Discriminative performance for each predictor was compared using receiver-operator characteristics (ROC) curves. RESULTS: Baseline Central Mechanisms trait scores predicted pain persistence (Relative Risk, RR = 2.10, P = 0.001) and persistent pain severity (β = 0.47, P < 0.001), even after adjustment for age, sex, BMI, radiographic scores and symptom duration. Baseline joint-line PPTs also associated with pain persistence (RR range = 0.65 to 0.68, P < 0.02), but only in univariate models. Lower baseline medial joint-line PPT was associated with persistent pain severity (β = -0.29, P = 0.013) in a fully adjusted model. The Central Mechanisms trait model showed good discrimination of pain persistence cases from resolved pain cases (Area Under the Curve, AUC = 0.70). The discrimination power of other predictors (PPTs (AUC range = 0.51 to 0.59), radiographic OA (AUC = 0.62), age, sex and BMI (AUC range = 0.51 to 0.64), improved significantly (P < 0.05) when the central mechanisms trait was included in each logistic regression model (AUC range = 0.69 to 0.74). CONCLUSION: A simple summary self-report Central Mechanisms trait score may indicate a contribution of central mechanisms to poor knee pain prognosis.
31420809 Altered expression of circular RNA in primary Sjögren's syndrome. 2019 Dec OBJECTIVES: This study evaluated expression of circRNA in primary Sjögren's syndrome (pSS) patients so as to find novel biomarkers for pSS screening and discussed possible role of circRNA in pSS. We also evaluated expression profile of circRNA in systemic lupus erythematosus (SLE) patients. METHODS: Microarray analysis detected circRNA expression in PBMCs from five paired pSS, SLE patients, and controls. Then, differentially expressed circRNAs were validated in 30 pSS patients as compared to 30 SLE patients, healthy controls. CircRNAs interacting with miRNAs were discussed by Arraystar's homemade miRNA target prediction software. ROC analysis assessed the diagnostic value. RESULTS: We identified 234 differentially expressed circRNAs in pSS patients and verified five selected circRNAs (including hsa_circRNA_001264, hsa_circRNA_104121, hsa_circRNA_045355, hsa_circRNA_103461, hsa_circRNA_105034). Expression of hsa_circRNA_001264, hsa_circRNA_104121, and hsa_circRNA_045355 was strongly related to some clinical, laboratory parameters, and disease activity index in pSS patients. ROC analysis indicated potential diagnostic ability for the three circRNAs in pSS patients. One hundred and forty-eight circRNAs were differently expressed between lupus patients and controls. CONCLUSION: This study provides evidence that hsa_circRNA_001264, hsa_circRNA_104121, and hsa_circRNA_045355 might be biomarkers for pSS, correlate with pSS etiology.Key Points• Many circRNAs were dysregulated in pSS patients.• Differentially expressed circRNAs correlated with pSS clinical, laboratory features.• CircRNAs may be biomarkers for pSS.
31287407 Evaluation of salivary gland ultrasonography in primary Sjögren's syndrome: does it refle 2019 May OBJECTIVES: To evaluate associations between salivary gland ultrasonography (SGUS) and clinical characteristics, disease activity and outcome in patients with primary Sjögren's syndrome (pSS). METHODS: The parotid and submandibular salivary glands were examined by ultrasonography using two different scoring systems proposed by Hocevar et al. and Milic et al. on 85 pSS patients. Patients with inhomogeneity/hypoechoic areas with scores ≥2 in parotid and submandibular glands were classified as severe parotid or severe submandibular involvements, respectively. Disease activity and patient-reported severity were evaluated using the European League Against Rheumatism Sjögren's Disease Activity Index (ESSDAI) and the European League Against Rheumatism Sjögren's Patient Reported Index (ESSPRI). Salivary gland functional capacity was investigated by unstimulated whole saliva flow rate (U-WSFR). RESULTS: Of the activity scores, ESSPRI dryness component was higher in pSS patients who had scores above the cut-off values for Hocevar (6.1±2.3 vs. 4.9±2.6, p=0.026). The patients with any type of systemic involvement more frequently showed higher SGUS scores, according to both Hocevar (72.4 vs. 44.6%, p=0.013) and Milic (75.9 vs. 51.8%, p=0.026). These patients also showed a higher percentage of severe parotid/submandibular changes on US imaging (65.5 vs. 33.9%, p=0.005 and 75.9 vs. 51.8%, p=0.026 respectively). Higher SGUS scores according to cut-off values of both scoring systems and severe parotid/submandibular involvements were associated with both anti-Ro or double anti-Ro/La autoantibodies and inversely associated with U-WSFR. CONCLUSIONS: SGUS may be a useful imaging modality for the selection of patients with more severe disease status or who may require a tight follow-up schedule.
30805374 Shared Medical and Environmental Risk Factors in Dry Eye Syndrome, Sjogren's Syndrome, and 2019 OBJECTIVES: To assess whether there are shared exposures associated with Sjogren's syndrome (SS), dry eye syndrome (DES), and B-cell non-Hodgkin lymphoma (B-NHL), in order to determine whether they are etiologically related. METHODS: In a clinic-based case-control study, 702 participants (91 SS, 120 DES, 211 (age and sex frequency-matched) controls, and 280 B-NHL cases) were recruited and interviewed regarding exposures, medical history, and family history. RESULTS: Female predominance was noted in SS (ratio 9.2 : 1). Eye dryness was severest in SS compared to DES and controls (P < 0.001). Compared to controls, alcohol consumption was inversely associated with NHL, DES, and SS (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.31-0.71; OR = 0.54, 95% CI: 0.33-0.88; and OR = 0.26, 95% CI: 0.14-0.49, respectively), while a previous history of infection requiring hospitalization was positively associated with all three conditions: NHL (OR = 1.92; 95% CI: 1.23-2.99), DES (OR = 3.29; 95% CI: 1.97-5.47), and SS (OR = 4.74; 95% CI: 2.66-8.44). NHL patients were more likely to report first-degree relatives with hematologic cancer, while having first-degree relatives with an autoimmune disease (AID) was associated with SS (OR = 5.25; 95% CI: 2.59-10.63) and DES (OR = 3.55; 95% CI: 1.83-6.91) compared to controls. CONCLUSIONS: Some exposures are associated with all three conditions (such as an inverse association with alcohol consumption and a positive association with serious past infection), while a family history of AID appears to be shared by DES and SS, but not NHL subjects. Shared risk factors for all three conditions indicate possible mutual etiological pathways.
30763687 Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between 2019 Oct OBJECTIVE: Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. METHODS: Outpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. RESULTS: Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76-1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42-0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. CONCLUSION: Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.
30401509 Comparative Assessment of Hand Joint Ultrasound Findings in Symptomatic Patients with Syst 2019 Feb Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) can be associated with inflammatory arthritis, which is underdiagnosed by clinical examination. The aim of this cross-sectional, observational study was to compare, for the first time, the ultrasound (US)-detected joint abnormalities in these two diseases and to define the role of US in patient management. Participants had SLE (n = 18) and SS (n = 23), symptoms of hand joint pain and no previous diagnosis of arthritis. Data on disease activity, duration, damage scores, inflammatory and serologic markers, treatment and clinical and ultrasound parameters (derived from the assessment of 902 joints) were analysed and correlated using descriptive statistics, correlation tests and regression models. Subclinical synovitis/tenosynovitis was detected in 44.4% of SLE patients and 21.7% of SS patients (p = 0.23). There was no significant correlation between either the total Power Doppler score or the total grey-scale score and disease activity scores (British Isles Lupus Assessment Group index and European League Against Rheumatism Sjögren's syndrome disease activity index). Both damage scores (Systemic Lupus International Collaborating Clinics index and Sjögren's syndrome disease damage index) correlated with the total grey-scale synovitis score. Significant proportions of the participants with SLE and SS had erosions (55.6% and 34.8%, respectively, p = 0.184) and osteophytes (61.1% vs. 60.9%, p = 0.98) in at least one joint. The lack of correlation between disease activity scores and US outcome measures indicated their limitations in diagnosing subclinical synovitis in SLE and SS patients. Future research is needed to determine if the development of erosions could be prevented by early diagnosis and prompt treatment of inflammatory arthritis associated with SLE and SS.