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ID PMID Title PublicationDate abstract
31777818 Binding Immunoglobulin Protein (BIP) Inhibits TNF-α-Induced Osteoclast Differentiation an 2019 Aug OBJECTIVE: The association between inflammation and dysregulated bone remodeling is apparent in rheumatoid arthritis and is recapitulated in the human tumor necrosis factor transgenic (hTNFtg) mouse model. We investigated whether extracellular binding immunoglobulin protein (BiP) would protect the hTNFtg mouse from both inflammatory arthritis as well as extensive systemic bone loss and whether BiP had direct antiosteoclast properties in vitro. METHODS: hTNFtg mice received a single intraperitoneal administration of BiP at onset of arthritis. Clinical disease parameters were measured weekly. Bone analysis was performed by microcomputed tomography and histomorphometry. Mouse bone marrow macrophage and human peripheral blood monocyte precursors were used to study the direct effect of BiP on osteoclast differentiation and function in vitro. Monocyte and osteoclast signaling was analyzed by Western blotting, flow cytometry, and imaging flow cytometry. RESULTS: BiP-treated mice showed reduced inflammation and cartilage destruction, and histomorphometric analysis revealed a decrease in osteoclast number with protection from systemic bone loss. Abrogation of osteoclast function was also observed in an ex vivo murine calvarial model. BiP inhibited differentiation of osteoclast precursors and prevented bone resorption by mature osteoclasts in vitro. BiP also induced downregulation of CD115/c-Fms and Receptor Activator of NF-κB (RANK) messenger RNA and protein, causing reduced phosphorylation of the p38 mitogen-activated protein kinases, extracellular signal-regulated kinases 1/2 and p38, with suppression of essential osteoclast transcription factors, c-Fos and NFATc1. BiP directly inhibited TNF-α- or Receptor Activator of NF-κB Ligand (RANKL)-induced NF-κB nuclear translocation in THP-1 monocytic cells and preosteoclasts by the canonical and noncanonical pathways. CONCLUSION: BiP combines an anti-inflammatory function with antiosteoclast activity, which establishes it as a potential novel therapeutic for inflammatory disorders associated with bone loss.
30449652 Palliative and end-of-life care in rheumatology: High symptom prevalence and unmet needs. 2019 Aug OBJECTIVES: To determine the extent of end-of-life suffering and predictors of high symptom prevalence in the last one year of life in patients with systemic rheumatic diseases (SRDs) and the extent of supportive care received. METHODS: We identified adult patients with SRDs who died between 1 April 2006 and 1 April 2016. We collected data within 1 year before their death, on the following: (i) cumulative symptom prevalence, (ii) rates of Advance Care Planning (ACP), Do-Not-Resuscitate (DNR) orders and referral to a palliative physician. We analyzed the predictors of total symptom prevalence and palliative physician referral. RESULTS: Of the 161 patients studied, 34.2% had rheumatoid arthritis and 21.6% had systemic lupus erythematosus. Pain (81.4%), anorexia (80.1%) and dyspnea (77%) afflicted the majority of patients. On multivariate analysis, patients of the following profile had higher total symptom prevalence: (i) older age (β = 0.027, SE = 0.013, p = 0.044); (ii) more comorbidities measured by the Charlson Comorbidity Index (β = 0.192, SE = 0.159, p = 0.044); (iii) more admissions (β = 0.263, SE = 0.090, p = 0.004) and (iv) recurrent infections (β = 0.923, SE = 0.423, p = 0.031). Five patients (3.1%) received ACP and 25 (15.5%) were referred to a palliative physician. The median time between referral to palliative medicine and death was 8 days (IQR0-19). Of the 106 (67.5%) who had DNR orders, the median time between DNR and death was 3 days (IQR 0-10). CONCLUSIONS: Palliative and supportive care is relevant to patients with SRDs at the end-of-life. These patients experienced high physical suffering, particularly those who were elderly, with more comorbidities, hospital admissions and recurrent infections. Rheumatologists and physicians caring for patients with SRDs must be empowered to provide supportive care to these patients at the last phase of life, particularly by facilitating early ACP.
31308681 Urinary orosomucoid: a new marker of cardiovascular risk in psoriatic patients? 2019 PURPOSE: Psoriasis is one of the most common lifelong lasting dermatologic diseases. According to the latest studies, psoriatic patients have a higher risk of developing cardiovascular diseases. Psoriasis is considered as a systemic inflammatory disease. Several oxidative stress markers have been shown to be elevated in psoriasis. However, a panel of biomarkers has not been used yet. This study was aimed at exploring the connection between a panel of biomarkers (C-reactive protein, asymmetric dimethylarginine, uric acid, total antioxidant capacity, malondialdehyde, and orosomucoid [ORM]) and cardiovascular risk in psoriatic patients. PATIENTS AND METHODS: The inclusion criterion was the onset of psoriasis with skin lesions. Exclusion criteria were impaired renal function (eGFR<60 mL/min/1.73 m(2)), acute inflammations (urinary, respiratory, skin inflammation, etc), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, or inflammatory bowel disease), and any kind of biological antipsoriatic treatment. Patients with a medical history of myocardial infarction, coronary heart disease, stroke, transient ischemic attack, and carotid artery stenosis were also excluded. Biomarkers were measured by routine procedures, ELISA and HPLC. QRISK®2-2017 was used to assess 10-year risk of cardiovascular disease development. Psoriasis severity was measured by the Psoriasis Area and Severity Index. RESULTS: One hundred and fourteen psoriatic patients were enrolled. Only urinary orosomucoid and urinary orosomucoid/urinary creatinine (u-ORM/u-CREAT) ratio showed significant correlation with QRISK score (u-ORM, r=0.245; u-ORM/u-CREAT, r=0.309). When comparing mild psoriatic patients to moderate psoriatic patients, significant differences could only be found in u-ORM and u-ORM/u-CREAT ratio. CONCLUSION: There seems to be a connection between urinary ORM and cardiovascular risk. U-ORM and u-ORM/u-CREAT ratio could be used as an indicator of low-grade inflammation in mild and moderate psoriasis. However, it is the 10-year follow-up of cardiovascular events that will determine the usefulness of this biomarker panel.
28923429 Frequency of auditory involvement and of associated factors in patients with juvenile idio 2019 May INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by the presence of arthritis in children under 16 years of age for more than 6 weeks in the absence of any other known cause. The extra-articular manifestations, especially in the audiovestibular system, are related to the involvement of the joints of the ossicular chain as a result of the inflammatory process in the synovium. Previous clinical studies in pediatric patients have shown conductive or sensorineural hearing loss. OBJECTIVE: The aim of this study was to assess the frequency of hearing impairment and of associated factors in patients with JIA. METHODOLOGY: A prospective, analytical study was conducted from January 2013 to August 2014 in 62 patients with JIA aged between 5 and 15 years. The study was approved by the local ethics committee and parents signed their informed consent. All subjects underwent audiological examination involving otomicroscopy, audiometry, tympanometry, stapedius reflex and test for transient otoacoustic emissions (TOAE); rheumatologic evaluation included joint examination and the application of a measure of functional ability (disability) using the Childhood Health Assessment Questionnaire (CHAQ). Measures of central tendency and of dispersion were used (chi-square for associations and P<.05 for statistical significance). RESULTS: Sixty-two patients were included: 56 girls and 6 boys, mean age 11.9 years and mean disease duration of 3.4 years; 46% had rheumatoid factor (RF)- positive polyarticular JIA, 40% had RF-negative polyarticular JIA, 15% had disease of systemic onset and 3% had oligoarthritis. Active disease was found in 29 patients and 33 were in remission with medication. Of the total of 124 ears evaluated according to the Jerger classification for tympanometry, abnormal findings were observed in 78 that were type As and in 1 that was type Ad, whereas there were 45 type A ears. Hearing loss was disclosed by speech audiometry, rather than by pure tone audiometry. The TOAE were absent in 4% of those assessed and the stapedius reflex was absent in less than 10%. Factors that had a positive correlation with hearing impairment were RF-positive polyarticular JIA, disease duration, degree of disability and the erythrocyte sedimentation rate level (P<.000). CONCLUSION: The presence of an abnormal tympanogram suggested early involvement in the structure of the tympanic-ossicular complex; however, 3.4 years later, no hearing loss had been reported.
31063606 Multimodal [(18) F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitud 2019 Sep In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([(18) F]FDG) and [(18) F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [(18) F]FDG, for detecting inflammatory processes, or [(18) F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV(mean) ) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [(18) F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [(18) F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [(18) F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
30358903 Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase enzymes in relation to infl 2019 Jan OBJECTIVE: Patients with chronic kidney disease (CKD) have dysregulated cortisol metabolism secondary to changes in 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes. The determinants of this and its clinical implications are poorly defined. METHODS: We performed a cross-sectional study to characterize shifts in cortisol metabolism in relation to renal function, inflammation and glycaemic control. Systemic activation of cortisol by 11β-HSD was measured as the metabolite ratio (tetrahydrocortisol [THF]+5α-tetrahydrocortisol [5αTHF])/tetrahydrocortisone (THE) in urine. RESULTS: The cohort included 342 participants with a median age of 63 years, median estimated glomerular filtration rate (eGFR) of 28 mL/min/1.73 m(2) and median urine albumin-creatinine ratio of 35.5 mg/mmol. (THF+5αTHF)/THE correlated negatively with eGFR (Spearman's ρ = -0.116, P = 0.032) and positively with C-reactive protein (ρ = 0.208, P < 0.001). In multivariable analysis, C-reactive protein remained a significant independent predictor of (THF+5αTHF)/THE, but eGFR did not. Elevated (THF+5αTHF)/THE was associated with HbA1c (ρ = 0.144, P = 0.008) and diabetes mellitus (odds ratio for high vs low tertile of (THF+5αTHF)/THE 2.57, 95% confidence interval 1.47-4.47). Associations with diabetes mellitus and with HbA1c among the diabetic subgroup were independent of eGFR, C-reactive protein, age, sex and ethnicity. CONCLUSIONS: In summary, glucocorticoid activation by 11β-HSD in our cohort comprising a spectrum of renal function was associated with inflammation and impaired glucose control.
31260471 LL-37 alone and in combination with IL17A enhances proinflammatory cytokine expression in 2019 LL-37 is the only human cathelicidin-family host defense peptide and has been reported to interact with invading pathogens causing inflammation at various body sites. Recent studies showed high levels of LL-37 in the synovial-lining membrane of patients with rheumatoid arthritis, a common type of inflammatory arthritis. The present study aims to investigate the role of LL-37 on mechanisms associated with pathogenesis of inflammatory arthritis. The effects of LL-37 on the expression of proinflammatory cytokines, hyaluronan (HA) metabolism-related genes, cell death-related pathways, and cell invasion were investigated in SW982, a human synovial sarcoma cell line. Time-course measurements of proinflammatory cytokines and mediators showed that LL-37 significantly induced IL6 and IL17A mRNA levels at early time points (3-6 hr). HA-metabolism-related genes (i.e., HA synthase 2 (HAS2), HAS3, hyaluronidase 1 (HYAL1), HYAL2, and CD44) were co-expressed in parallel. In combination, LL-37 and IL17A significantly enhanced PTGS2, TNF, and HAS3 gene expression concomitantly with the elevation of their respective products, PGE2, TNF, and HA. Cell invasion rates and FN1 gene expression were also significantly enhanced. However, LL-37 alone or combined with IL17A did not affect cell mortality or cell cycle. Treatment of SW982 cells with both LL-37 and IL17A significantly enhanced IKK and p65 phosphorylation. These findings suggest that the chronic production of a high level of LL-37 may synchronize with its downstream proinflammatory cytokines, especially IL17A, contributing to the co-operative enhancement of pathogenesis mechanisms of inflammatory arthritis, such as high production of proinflammatory cytokines and mediators together with the activation of HA-metabolism-associated genes and cell invasion.
31814574 Platelet parameters aid identification of adult-onset Still's disease from sepsis. 2019 Oct BACKGROUND: Adult-onset Still's disease (AOSD) is a rare, chronic, and systemic inflammatory disorder. The current study aims to evaluate the ability of platelets (PLTs), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and PLT to PDW ratio (PPR) in a cohort of patients with AOSD or sepsis. METHODS: Serum samples were obtained from 82 AOSD patients, 48 sepsis patients, and 76 matched healthy controls. Platelet parameters were measured by Sysmex XE 2100 analysers. RESULTS: PPR and ferritin in AOSD patients were significantly higher than those in sepsis patients (22.18 ±; 11.12 vs. 13.80 ±; 8.97, p < 0.001; 3972.90 ±; 5134.04 μg/l vs. 518.92 ±; 382.50 μg/l, p = 0.001, respectively) and they were independent factors to differentiate AOSD from sepsis (OR: 5.86, 95%CI 1.59-21.60, p = 0.008; OR: 54.06, 95%CI 9.57-305.44, p < 0.001; respectively). Furthermore, PPR in AOSD and sepsis was significantly higher than that in matched controls. The area under the ROC curve of PPR, ferritin, and the combination were 0.733 (95%CI 0.646-0.820), 0.887 (95%CI 0.825-0.950), and 0.931 (95%CI 0.884-0.984), respectively. CONCLUSION: PPR can be used as a useful marker to differentiate AOSD from sepsis and the combined identification value of PPR and ferritin is much higher than that of any single factor.
28379880 Immunoresponsive Autonomic Neuropathy in Sjögren Syndrome-Case Series and Literature Revi 2019 Jan/Feb BACKGROUND: Sjögren syndrome (SS) is one of the most common autoimmune disorders that classically affects exocrine glands, resulting in keratoconjunctivitis sicca and xerostomia, and frequently is associated with other systemic symptoms. SS appears to have a particular predilection for involving the autonomic nervous system. STUDY QUESTION: Does immunotherapy improve signs and symptoms of autonomic nervous system impairment in SS? STUDY DESIGN: This is a retrospective review of patients seen in the autonomic clinic at our institution who underwent an evaluation for a suspected autonomic disorder that ultimately was attributed to SS. SS patients who were treated with immunotherapy and completed autonomic testing before and after treatment were included in this review. RESULTS: A total of 4 patients were identified who were treated for SS-related autonomic dysfunction with immunotherapy and underwent repeat autonomic testing after treatment. Marked clinical and functional improvement was seen after treatment with intravenous immunoglobulin in all patients and adjunctive rituximab therapy in 1 patient. The clinical improvement with immunotherapy in these patients correlated with markedly improved findings on autonomic testing in all. MEASURES AND OUTCOMES: Clinical symptoms and results of autonomic testing prior to and following immunotherapy were assessed. CONCLUSIONS: Autonomic signs and symptoms in SS are potentially immunoresponsive, but immunotherapy in these patients may require repeated, ongoing, or adjunctive therapy for optimal and sustained improvement.
31692065 Clinical significance of serum bilirubin in primary Sjögren syndrome patients. 2020 Mar OBJECTIVE: The purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS). PATIENTS AND METHODS: A total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed. RESULTS: Serum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = -.406, P < .001; r = -.206, P = .026; r = -.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR. CONCLUSIONS: This study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow-up visits of the patients with pSS.
31318961 Evaluation of macrophage activation syndrome in hospitalised patients with Kikuchi-Fujimot 2019 BACKGROUND: To evaluate the impact of macrophage activation syndrome (MAS) on clinical features in patients with Kikuchi-Fujimoto disease (KFD) and to compare the features of MAS in KFD with those of adult-onset Still's disease (AOSD) and systemic lupus erythematosus (SLE). METHODS: The medical records of febrile patients hospitalised with KFD between November 2005 and April 2017 were reviewed. Patients fulfilling the 2016 classification criteria for MAS were classified as having MAS. Clinical and laboratory features of patients with KFD with and without MAS were evaluated. Poor hospitalisation outcomes were defined as intensive care unit admission or in-hospital mortality. The treatment outcomes of MAS in KFD, AOSD, and SLE were also compared. RESULTS: Among 78 patients hospitalised with KFD, 24 (30.8%) patients had MAS during admission. Patients with KFD and MAS more frequently required glucocorticoid treatment (66.7% vs 40.7%, p = 0.036) and had longer hospital stays than patients with KFD without MAS (12.5 vs 8.5 days, p<0.001). In addition, patients with MAS had worse hospitalisation outcomes than patients without MAS (29.2% vs. 0.0%, p<0.001). Among patients with MAS in KFD, AOSD, and SLE, the number of patients requiring glucocorticoid treatment after 3 months was significantly lower among patients with MAS and KFD (KFD 33.3%, AOSD 88.9%, SLE 100%, p<0.001). CONCLUSIONS: The presence of MAS in KFD was associated with adverse clinical outcomes including higher steroid usage and worse hospitalisation outcomes. However, compared to those with AOSD and SLE, patients with MAS and KFD were less likely to require long-term glucocorticoid treatment.
30817584 Characteristics of dry eye in patients with pre-existing Sjögren's syndrome according to 2019 Mar To compare the characteristics of dry eye (DE) patients who did and did not satisfy the 2016 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (SS) among patients with pre-existing SS diagnosed according to the 2012 ACR criteriaThis cross-sectional study evaluated 91 patients with pre-existing SS and 55 with non-SS DE. Patients with SS were divided into 2 groups according to whether they met the revised 2016 ACR-EULAR classification criteria for primary SS. Group 1 (n = 71) was comprised of patients who satisfied the revised 2016 criteria and group 2 (n = 20) was comprised of patients who did not satisfy the newly revised criteria. Group 3 consisted of 55 patients with non-SS DE. The ocular surface disease index (OSDI) score, tear break-up time (TBUT), Schirmer score, tear clearance rate (TCR), and corneal and conjunctival staining scores were evaluated and compared between the groups. Laboratory profiles, including antinuclear antibodies, rheumatoid factor levels, erythrocyte sedimentation rate, and C-reactive protein levels, and focus scores were analyzed.TBUT, Schirmer, and corneal/conjunctival staining scores were significantly worse in both groups of patients with SS (groups 1 and 2) than in those with non-SS DE (group 3). However, there were no significant differences between groups 1 and 2 in laboratory findings as well as in ocular surface findings, including OSDI, TBUT, Schirmer score, TCR, and corneal/conjunctival staining scores. The focus score, which shows the level of lymphocytic infiltration in the salivary glands, was higher in group 1 than in group.Of the patients with pre-existing SS who were diagnosed according to the 2012 ACR classification, patients who did not satisfy the 2016 ACR-EULAR classification criteria for primary SS showed similar ocular surface parameters and laboratory findings to patients who did meet the revised classification, except for focus score. There is no need to change the direction of treatment of DE in patients with pre-existing SS who did not meet the revised 2016 ACR-EULAR criteria.
31769856 Anakinra in children and adults with Still's disease. 2019 Nov 1 Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these being one disease-Still's disease-with different ages of onset. Anakinra was recently approved by the European Medicines Agency for Still's disease. In this review we discuss the reasoning for considering Still's disease as one disease and present anakinra efficacy and safety based on the available literature. The analysis of 27 studies showed that response to anakinra in Still's disease was remarkable, with clinically inactive disease or the equivalent reported for 23-100% of patients. Glucocorticoid reduction and/or stoppage was reported universally across the studies. In studies on paediatric patients where anakinra was used early or as first-line treatment, clinically inactive disease and successful anakinra tapering/stopping occurred in >50% of patients. Overall, current data support targeted therapy with anakinra in Still's disease since it improves clinical outcome, especially if initiated early in the disease course.
31042125 Right ventricular thrombus in a case of neonatal lupus: case report. 2019 May Neonatal thrombosis is considered a rare manifestation with unclear aetiology. We reported a neonatal lupus of a Sjogren's syndrome mother with recurrent miscarriage secondary to antiphospholipid syndrome; seronegative to anticardiolipin antibodies, lupus anticoagulant and B2GP1. She was serologically positive to antiphosphatidylethanolamine and antiprothrombin antibodies, anti-SSA/Ro and anti-SSB/La. The neonate developed neonatal lupus complicated with right ventricular thrombus assumed to be induced by maternal transmission of antiphosphatidylethanolamine and antiprothrombin antibodies, treated successfully with tissue plasminogen activator and warfarin.
31010136 Tear Proteomics Approach to Monitoring Sjögren Syndrome or Dry Eye Disease. 2019 Apr 19 Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components to allow for SS-DED monitoring and avoid stably controlled SS-DED patients from re-entering a vicious cycle. This prospective case-control study compared stable SS-DED patients with non-SS-DED control from several aspects, including clinical indices for TF homeostasis, 2 DED diagnostic biomarkers (MMP-9 and lactoferrin), and the proteome of flush tears. Compared with non-SS-DED controls, stably controlled SS-DED subjects had less tear secretion and higher ocular surface inflammation, a higher concentration ratio of tear MMP-9/lactoferrin, a more diverse tear proteome, and lower spectral intensities of lipocalin-1, lacritin, and prolactin-inducible protein among the abundant tear proteins. For stable SS-DED patients, the concentration ratio of tear MMP-9/lactoferrin and the corrected lipocalin-1 signal was positively correlated with ocular inflammation and TF stability, respectively. MMP-9 released from stressed ocular surface epithelium and lipocalin-1 secreted from the energetic lacrimal gland are two tear biomarkers responding well to TF homeostasis. The tear proteomics approach through flush tears is a promising method for monitoring SS-DED patients with a standardized sampling procedure and lactoferrin-corrected analysis.
30936275 Considerations for Evaluating and Recommending Worker Productivity Outcome Measures: An Up 2019 Oct OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Worker Productivity Group continues efforts to assess psychometric properties of measures of presenteeism. METHODS: Psychometric properties of single-item and dual answer multiitem scales were assessed, as well as methods to evaluate thresholds of meaning. RESULTS: Test-retest reliability and construct validity of single item global measures was moderate to good. The value of measuring both degree of difficulty and amount of time with difficulty in multiitems questionnaires was confirmed. Thresholds of meaning vary depending on methods and external anchors applied. CONCLUSION: We have advanced our understanding of the performance of presenteeism measures and have developed approaches to describing thresholds of meaning.
30813268 Chronic Hepatitis E in Rheumatology and Internal Medicine Patients: A Retrospective Multic 2019 Feb 22 Objectives: Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine patients, are at risk of developing chronic HEV infection is unclear. Methods: We conducted a retrospective European multicenter cohort study involving 21 rheumatology and internal medicine patients with HEV infection between April 2014 and April 2016. The underlying diseases included rheumatoid arthritis (n = 5), psoriatic arthritis (n = 4), other variants of chronic arthritis (n = 4), primary immunodeficiency (n = 3), systemic granulomatosis (n = 2), lupus erythematosus (n = 1), Erdheim⁻Chester disease (n = 1), and retroperitoneal fibrosis (n = 1). Results: HEV infection lasting longer than 3 months was observed in seven (33%) patients, including two (40%) patients with rheumatoid arthritis, three (100%) patients with primary immunodeficiency, one (100%) patient with retroperitoneal fibrosis and one (100%) patient with systemic granulomatosis. Patients with HEV infection lasting longer than 3 months were treated with methotrexate without corticosteroids (n = 2), mycophenolate mofetil/prednisone (n = 1), and sirolimus/prednisone (n = 1). Overall, 8/21 (38%) and 11/21 (52%) patients cleared HEV with and without ribavirin treatment, respectively. One patient experienced an HEV relapse after initially successful ribavirin therapy. One patient (5%) was lost to follow-up, and no patients died from hepatic complications. Conclusion: Rheumatology and internal medicine patients, including patients treated with methotrexate without corticosteroids, are at risk of developing chronic HEV infection. Rheumatology and internal medicine patients with abnormal liver tests should be screened for HEV infection.
30219766 Presence of Autoantibodies in Erosive Hand Osteoarthritis and Association with Clinical Pr 2019 Jan OBJECTIVE: To investigate whether 3 rheumatoid arthritis-associated antibodies [rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) or anticarbamylated protein (anti-CarP) antibodies] are present in hand osteoarthritis (HOA) and associate with erosive OA (EOA). METHODS: Anti-CarP IgG was measured by ELISA in baseline sera of patients with HOA from 3 cohorts: HOSTAS (n = 510, 27.2% EOA), ECHO (n = 47), and EHOA (n = 23), and in sera of healthy controls (HC; n = 196, mean age 44.1 yrs, 51.0% women). Moreover, ACPA-IgG and RF-IgM were additionally determined in HOSTAS and HC. The prevalence of autoantibodies was compared between HOA and HC and between erosive and nonerosive HOA. In HOSTAS, hand radiographs were scored (Kellgren-Lawrence, Osteoarthritis Research Society International osteophyte and joint space narrowing) and C-reactive protein (CRP) levels, representing inflammation, were assessed. Groups were compared using nonparametric tests. RESULTS: The prevalence of anti-CarP was low and not significantly different between the total HOA group and HC (6.6% vs 3.6%, p = 0.12). In HOSTAS, the prevalence of all tested autoantibodies was low (anti-CarP 7.1%, ACPA 0.8%, RF 6.1%), and there were no significant differences observed between HOA patients and HC or between erosive and nonerosive HOA. Further, radiographic damage and CRP levels were similar in anti-CarP+ and anti-CarP-, and RF+ and RF- HOSTAS patients. CONCLUSION: The prevalence of autoantibodies is similar in HOA patients and HC, and these autoantibodies are not associated with erosive disease, structural damage, or inflammation in patients with HOA, indicating that another mechanism is driving erosive disease.
31234141 Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans. 2019 Jul Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n = 101) and polymyalgia rheumatica (PMR, n = 21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and sex-matched controls (-40%, P < 0.01 and -26.5%, P < 0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.
31024609 Genome-Wide DNA Methylation Profiles Reveal Common Epigenetic Patterns of Interferon-Relat 2019 Graves' disease (GD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are complex autoimmune diseases sharing common clinical, genetic and pathogenetic features. However, the commonalities of the DNA methylation profiles for these diseases are still unknown. We conducted an integrative analysis of the multiple-autoimmune disease methylation dataset including GD, RA, SLE, and SSc samples, to identify the common methylation patterns of autoimmune diseases. We identified 15,289 differentially methylated sites between multiple-autoimmune disease patients and controls in CD4+ T cells. We found that the most significant differentially methylated sites had a remarkable enrichment in type I interferon (IFN) pathway genes. Similarly, we identified 9,295 differentially methylated sites between GD/SSc patients and controls in CD8+ T cells. The overall IFN-related gene panel annotated by gene ontology (GO) showed an excellent diagnostic capacity in CD4+ T cells (Sensitivity = 0.82, specificity = 0.82 and AUC = 0.90), while IFI44L, another IFN-related gene not annotated by GO, showed high prediction ability in both CD4+ (AUC = 0.86) and CD8+ (AUC = 0.75) T cells. In conclusion, our study demonstrated that hypomethylation of IFN-related genes is a common feature of GD/RA/SLE/SSc patients in CD4+ T cells, and the DNA methylation profile of IFN-related genes could be promising biomarkers for the diagnosis of GD, RA, SLE, and SSc.