Browse

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

ID PMID Title PublicationDate abstract
34209508 Angiogenic Properties of NK Cells in Cancer and Other Angiogenesis-Dependent Diseases. 2021 Jun 29 The pathogenesis of many serious diseases, including cancer, is closely related to disturbances in the angiogenesis process. Angiogenesis is essential for the progression of tumor growth and metastasis. The tumor microenvironment (TME) has immunosuppressive properties, which contribute to tumor expansion and angiogenesis. Similarly, the uterine microenvironment (UME) exerts a tolerogenic (immunosuppressive) and proangiogenic effect on its cells, promoting implantation and development of the embryo and placenta. In the TME and UME natural killer (NK) cells, which otherwise are capable of killing target cells autonomously, enter a state of reduced cytotoxicity or anergy. Both TME and UME are rich with factors (e.g., TGF-β, glycodelin, hypoxia), which support a conversion of NK cells to the low/non-cytotoxic, proangiogenic CD56(bright)CD16(low) phenotype. It is plausible that the phenomenon of acquiring proangiogenic and low cytotoxic features by NK cells is not only limited to cancer but is a common feature of different angiogenesis-dependent diseases (ADDs). In this review, we will discuss the role of NK cells in angiogenesis disturbances associated with cancer and other selected ADDs. Expanding the knowledge of the mechanisms responsible for angiogenesis and its disorders contributes to a better understanding of ADDs and may have therapeutic implications.
33811177 Impact of assessing patient-reported outcomes with mobile apps on patient-provider interac 2021 Apr OBJECTIVE: To explore the effect of apps measuring patient-reported outcomes (PROs) on patient-provider interaction in the rheumatic diseases in an observational setting. METHODS: Patients in the Swiss Clinical Quality Management in Rheumatic Diseases Registry were offered mobile apps (iDialog and COmPASS) to track disease status between rheumatology visits using validated PROs (Rheumatoid Arthritis Disease Activity Index-5 score, Bath Ankylosing Spondylitis Disease Activity Index score, Routine Assessment of Patient Index Data-3 score and Visual Analogue Scale score for pain, disease activity and skin symptoms). We assessed two aspects of patient-provider interaction: shared decision making (SDM) and physician awareness of disease fluctuations. We used logistic regressions to compare outcomes among patients who (1) used an app and discussed app data with their physician (app+discussion group), (2) used an app without discussing the data (app-only group) or (3) did not use any app (non-app users). RESULTS: 2111 patients were analysed, including 1799 non-app users, 150 app-only users and 162 app+discussion users (43% male; with 902 patients with rheumatoid arthritis, 766 patients with axial spondyloarthritis and 443 patients with psoriatic arthritis). App users were younger than non-app users (mean age of 47 vs 51 years, p<0.001). Compared with non-app users, the app+discussion group rated their rheumatologist more highly in SDM (OR 1.7, 95% CI 1.1 to 2.4) and physician awareness of disease fluctuations (OR 2.0, 95% CI 1.3 to 3.1). This improvement was absent in the app-only group. CONCLUSION: App users who discussed app data with their rheumatologist reported more favourably on patient-provider interactions than app users who did not and non-app users. Apps measuring PROs may contribute little to patient-provider interactions without integration of app data into care processes.
34859072 Comparative Risk of Incident Coronary Heart Disease Across Chronic Inflammatory Diseases. 2021 Background: Chronic inflammatory diseases (CIDs) are considered risk enhancing factors for coronary heart disease (CHD). However, sparse data exist regarding relative CHD risks across CIDs. Objective: Determine relative differences in CHD risk across multiple CIDs: psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), systemic sclerosis (SSc), and inflammatory bowel disease (IBD). Methods: The cohort included patients with CIDs and controls without CID in an urban medical system from 2000 to 2019. Patients with CIDs were frequency-matched with non-CID controls on demographics, hypertension, and diabetes. CHD was defined as myocardial infarction (MI), ischemic heart disease, and/or coronary revascularization based on validated administrative codes. Multivariable-adjusted Cox models were used to determine the risk of incident CHD and MI for each CID relative to non-CID controls. In secondary analyses, we compared CHD risk by disease severity within each CID. Results: Of 17,049 patients included for analysis, 619 had incident CHD (202 MI) over an average of 4.4 years of follow-up. The multivariable-adjusted risk of CHD was significantly higher for SLE [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.2, 3.2] and SSc (HR 2.1, 95% CI 1.2, 3.9). Patients with SLE also had a significantly higher risk of MI (HR 3.6, 95% CI 1.9, 6.8). When CIDs were categorized by markers of disease severity (C-reactive protein for all CIDs except HIV, for which CD4 T cell count was used), greater disease severity was associated with higher CHD risk across CIDs. Conclusions: Patients with SLE and SSc have a higher risk of CHD. CHD risk with HIV, RA, psoriasis, and IBD may only be elevated in those with greater disease severity. Clinicians should personalize CHD risk and treatment based on type and severity of CID.
34064447 Synovial Fluid Fatty Acid Profiles Are Differently Altered by Inflammatory Joint Pathologi 2021 May 4 Anomalies of fatty acid (FA) metabolism characterize osteoarthritis (OA) and rheumatoid arthritis (RA) in the knee joint. No previous study has investigated the synovial fluid (SF) FA manifestations in these aging-related inflammatory diseases in the shoulder. The present experiment compared the FA alterations between the shoulder and knee joints in patients with end-stage OA or end-stage RA. SF samples were collected during glenohumeral or knee joint surgery from trauma controls and from OA and RA patients (n = 42). The FA composition of SF total lipids was analyzed by gas chromatography with flame ionization and mass spectrometric detection and compared across cohorts. The FA signatures of trauma controls were mostly uniform in both anatomical locations. RA shoulders were characterized by elevated percentages of 20:4n-6 and 22:6n-3 and with reduced proportions of 18:1n-9. The FA profiles of OA and RA knees were relatively uniform and displayed lower proportions of 18:2n-6, 22:6n-3 and total n-6 polyunsaturated FAs (PUFAs). The results indicate location- and disease-dependent differences in the SF FA composition. These alterations in FA profiles and their potential implications for the production of PUFA-derived lipid mediators may affect joint lubrication, synovial inflammation and pannus formation as well as cartilage and bone degradation and contribute to the pathogeneses of inflammatory joint diseases.
34216315 Polycystic ovary syndrome: epidemiologic assessment of prevalence of systemic rheumatic an 2021 Dec BACKGROUND: Polycystic ovary syndrome (PCOS) causes anovulation and hyperandrogenism. Hormonal imbalance is known to contribute to systemic autoimmune diseases. OBJECTIVE: To examine the frequency of certain rheumatic diseases in PCOS. METHODS: This retrospective study utilized and analyzed electronic medical records from January 2004 through February 2020. A diagnosis of PCOS and specified rheumatic diseases was searched using ICD-9 and ICD-10 codes. A total of 754 adult patients with PCOS and 1,508 age- and body mass index-matched patients without PCOS were included. Frequencies of the rheumatic diseases were compared between PCOS and non-PCOS subjects or literature data. RESULTS: The prevalence of rheumatoid arthritis (RA) was found to be 2.25% (17/737) in the PCOS patients, numerically higher than 1.26% (19/1489) in the non-PCOS subjects. The difference was significant with a confidence level of 90% (1.04-3.15) but not at 95% with an odds ratio of 1.808 (95% CI = 0.934-3.4, p = 0.0747). When compared with the literature data from the US female population, the prevalence of RA in PCOS patients was significantly higher (2.25% vs. 1.40%, p < 0.0001). Among the autoimmune diseases examined, both systemic sclerosis (0.40% vs. 0.0%, p = 0.0369) and undifferentiated connective tissue disease (0.53% vs. 0.0%, p = 0.0123) were significantly more frequent in the PCOS patients than the non-PCOS. Additionally, PCOS patients had a significantly higher frequency of osteoarthritis than non-PCOS patients (5.44% vs. 2.92%, p = 0.0030) with an odds ratio of 1.913 (95% CI = 1.239-2.955). CONCLUSION: We have shown unprecedentedly that certain rheumatic diseases are more prevalent in PCOS. This study provides important insight into autoimmunity in association with PCOS. Key Points • Polycystic ovary syndrome is postulated to cause systemic autoimmune disease due to its hormonal imbalance. • We conducted the first epidemiologic assessment of the prevalence of systemic autoimmune diseases. • Certain autoimmune and rheumatic diseases are more prevalent in polycystic ovary syndrome.
33547685 DBA/1 mice display equivalent cardiac function to C57BL/6J mice. 2021 Apr NEW FINDINGS: What is the central question of this study? Do normal adult DBA/1 mice have cardiac function and performance equal to those of C57BL/6J mice? What is the main finding and its importance? Male adult DBA/1 mice show equivalent cardiac function to C57BL/6J mice up to 8 months old. Therefore, cardiac dysfunction could be investigated in an autoimmune diseases model established with DBA/1 mice. ABSTRACT: Cardiovascular mortality has been increasing, and in particular, cardiovascular damage caused by some chronic autoimmune diseases accounts for a large proportion of this. C57BL/6J mice have been used mostly in studies of cardiovascular diseases. However, for purposes of modelling, this strain of mouse has a very low incidence of some chronic immune diseases such as rheumatoid arthritis, to which instead DBA/1 mice are more susceptible. Basic cardiac function differs between mice with different genetic backgrounds. Therefore, we monitored cardiac function and structure of normal male C57BL/6J and DBA/1 mice for six consecutive months. Echocardiography was used to monitor cardiac functions once a month and cardiac systolic function was measured upon isoproterenol challenge at the end of observation. The Excitation-contraction coupling-related proteins were measured by western blotting. Heart tissue sections were subject to haematoxylin-eosin, TUNEL and Alizarin red staining. The results demonstrated that systolic and diastolic function did not vary significantly and both strains were indistinguishable in appearance and structure of hearts. DBA/1 mice showed a good cardiac β-adrenergic response comparable to C57BL/6J mice with isoproterenol treatment. The phosphorylation of phospholamban at either its protein kinase A or its Ca(2+) /calmodulin-dependent protein kinase II site, as well as the activation of troponin I showed no significant difference between strains. These findings suggested that there was no obvious difference in the heart structure and function of normal male DBA/1 mice compared with C57BL/6J mice. The DBA/1 mouse is a strain applicable to investigating autoimmune disease-induced heart dysfunction and exploring potential interventions.
34726121 Characteristics of participants and decliners from a randomized controlled trial on physic 2021 Nov 2 OBJECTIVE: A randomized controlled trial [Joint Resources - Sedentary Behaviour (JR-SB) intervention] aimed to reduce sedentary behaviour and increase light-intensity physical activity in patients with rheumatoid arthritis (RA) through motivational counselling and text messages. Since a large proportion of invited patients declined to participate, this study aims to compare sociodemographic, clinical, and lifestyle factors between included patients and patients declining to participate (non-participants) in the JR-SB study and to investigate which characteristics were associated with participation. METHOD: A register-based cross-sectional study was conducted. All patients invited to participate in the JR-SB study were identified in the DANBIO registry, from which patients' clinical and lifestyle data were also retrieved. Data on sociodemography and comorbidity were extracted from national registers. Differences between participants and non-participants were determined by an independent t-test or a chi-squared test. Logistic regression analyses adjusted for various confounders tested the association of patient characteristics with the likelihood of participation in the JR-SB study. RESULTS: A total of 467 (58%) declined participation in the JR-SB study. Non-participants were older and less educated, more were smokers, fewer performed regular physical activity, and more had comorbidity compared to participants. Regression analyses showed that a higher educational level and absence of comorbidity in particular were associated with participation in the JR-SB study. CONCLUSION: Patients with RA who are less educated and with certain types of comorbidity are less motivated to participate in a physical activity intervention. The findings may inform the recruitment process and implementation of physical activity interventions in rheumatology clinical practice.
34596027 Trajectories in early rheumatoid arthritis related fatigue over 10 years: results from the 2021 Sep 21 OBJECTIVES: In a cohort of early rheumatoid arthritis (RA) patients, we aimed to determine and characterise fatigue trajectories over 10 years of follow-up and identify predictors of trajectory membership. METHODS: We selected patients fulfilling the 2010 ACR/EULAR criteria for RA included in the ESPOIR cohort. We used a cluster analysis to obtain fatigue (assessed by fatigue visual analogue scale) trajectories over the course of 10 years from enrolment. Chi-square tests or ANOVA were performed to evaluate differences of baseline variables between fatigue trajectories. Using a multinomial logistic regression we were able to identify predictors of trajectory membership. RESULTS: We analysed 598 patients with mean disease duration at enrolment of 26.2±40.9 days. Cluster analysis revealed 3 trajectories: high (18%), moderate (52%) and low fatigue (30%). Compared to patients with moderate or low fatigue trajectory, patients with high fatigue trajectory were predominantly women and reported significantly higher duration and intensity of morning stiffness, HAQ score, tender joints count, levels of pain, number of awakenings due to arthritis, frequency of fibromyalgic RA, levels of physician and patient global assessment, more frequent sleep problems, and increased psychological distress. Female patients with pain, psychological distress and presence of sicca symptoms had a higher risk of being in the high trajectory group. CONCLUSIONS: These findings suggest that levels of fatigue are rather stable over time in each trajectory. Baseline clinical measures and baseline patient-reported measures of functional status better distinguished the three fatigue trajectories. We did not find any differences between trajectories in baseline laboratory measures. Inflammatory activity was not a predictor of being in the high trajectory fatigue group.
33650196 Examining the Relationship Between Rheumatoid Arthritis, Multimorbidity, and Adverse Healt 2021 Mar 1 OBJECTIVE: Multimorbidity (the coexistence of two or more long-term conditions) is highly prevalent in people who have rheumatoid arthritis (RA). The present work systematically reviewed the literature to determine the effect of multimorbidity on all-cause mortality, functional status, and quality of life in RA. METHODS: Six electronic databases were searched: CINAHL, The Cochrane Library, Embase, Medline, PsycINFO, and Scopus. Full-text longitudinal observational studies in English were selected. Quality appraisal of studies was undertaken using the Cochrane-developed QUIPS tool and a narrative synthesis of findings conducted. RESULTS: The search strategy identified 5,343 articles, with 19 studies meeting the inclusion criteria. Nine studies had mortality as an outcome, 9 reported functional status and/or quality of life, and 1 study reported both mortality and functional status. The number of participants ranged from 183 to 18,485, with studies conducted between 1985 and 2018. The mean age of participants ranged from 52.0 to 66.6 years, and 60.0-88.0% were female. Nine studies showed a significant association between multimorbidity and higher risk of mortality in people with RA. Ten studies reported significant associations between multimorbidity and reduced functional status in RA. Three studies also showed a further association with reduced quality of life. Only one study investigated the influence of mental health comorbidities on outcomes. CONCLUSION: Our review findings indicate that multimorbidity is a significant predictor for higher mortality and poorer functional status/quality of life in people with RA and should be considered in clinical management plans.
34535968 Effect of Training on Patient Self-Assessment of Joint Counts in Rheumatoid Arthritis: A S 2021 Dec OBJECTIVE: Patient self-assessed joint counts, if accurate and reliable, could potentially serve as a useful clinical assessment tool in rheumatoid arthritis (RA). This systematic review examines the effect of patient training on the inter-rater reliability of joint counts between patients and clinicians. METHODS: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was performed in PubMed, Embase, Cochrane Library, and CINAHL for articles that incorporated patient training and measured the reliability of patient self-assessed joint counts in RA. Articles were included if they reported on the inter-rater reliability between patient and clinician joint counts in both trained and untrained patients with RA. Data were extracted on characteristics of patients, structure and components of the training interventions, joint count reliability of patients with and without training, and patient feedback on training interventions. The relevant data were summarized and described. RESULTS: Multiple training methods have been studied (n = 5), including in-person sessions run by rheumatologists and instructional videos on the joint examination. Overall, training improved the reliability of patient self-joint counts, with more marked improvement in reliability of swollen joint counts than tender joint counts. Patients had positive feedback when surveyed on their experiences with training. CONCLUSION: Various training modalities (in-person and video-based) may be effective at improving reliability of patient self-joint counts. More research is needed on this topic, with potential areas for future research including 1) comparison between the efficacy of different modalities of training, and 2) impact of patient factors (education level and disease severity) on the efficacy of training.
33595914 A scoping Review of tools used to assess patient Complexity in rheumatic disease. 2021 Apr OBJECTIVE: Patients with rheumatic diseases often have multiple comorbidities which may impact well-being leading to high psychosocial complexity. This scoping review was undertaken to identify complexity measures/tools used in rheumatology that could help in planning and coordinating care. METHODS: MEDLINE, EMBASE and CINAHL were searched from database inception to 14 December 2019 using keywords and Medical Subject Headings for "care coordination", "complexity" and selected rheumatic diseases and known complexity measures/tools. Articles describing the development or use of complexity measures/tools in patients with adult rheumatologic diagnoses were included regardless of study design. Included articles were evaluated for risk of bias where applicable. RESULTS: The search yielded 407 articles, 37 underwent full-text review and 2 were identified during a hand search with 9 included articles. Only 2 complexity tools used in populations of adult patients with rheumatic disease were identified: the SLENQ and the INTERMED. The SLENQ is a 97-item patient needs questionnaire developed for patients with systemic lupus (n = 1 study describing tool development) and applied in 5 cross-sectional studies. Three studies (a practice article, trial and a cross-sectional study) applied the INTERMED, a clinical interview to ascertain complexity and support coordinated care, in patients with rheumatologic diagnoses. CONCLUSIONS: There is limited information on the use of patient complexity measures/tools in rheumatology. Such tools could be applied to coordinate multidisciplinary care and improve patient experience and outcomes. PATIENT CONTRIBUTION: This scoping review will be presented to patient research partners involved in co-designing a future study on patient complexity in rheumatic disease.
34208031 Emerging Role of microRNAs and Long Non-Coding RNAs in Sjögren's Syndrome. 2021 Jun 11 Sjögren's Syndrome (SS) is a chronic autoimmune inflammatory disease. It is considered a multifactorial pathology, in which underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to development. The epigenetic regulations represent a link between genetic predisposition and environmental factors. Recent studies suggested a regulatory role for non-coding RNAs in critical biological and disease processes. Among non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a critical role in the post-transcriptional mRNA expression, forming a complex network of gene expression regulation. This review aims to give an overview of the latest studies that have investigated the role of miRNAs and lncRNAs in the SS. We included papers that investigated the expression of non-coding RNAs on different tissues, in particular on peripheral blood mononuclear cells and salivary glands. However, regarding the involvement of non-coding RNAs genetic variability in SS susceptibility very few data are available. Further research could help to elucidate underlying pathogenic processes of SS and provide new opportunities for the development of targeted therapies.
33420523 Discovery® elbow system arthroplasty: results of 10-year follow-up. 2021 Aug BACKGROUND: The semi-constrained Discovery® Elbow System (LimaCorporate, San Daniele del Friuli, Italy) allows varus-valgus laxity of 7° [8]. It has been reported to provide good pain relief and increased range of motion [5, 9] on mid-term follow-up. The aim of the study was to evaluate long-term outcomes of total elbow arthroplasty using the Discovery® Elbow System (LimaCorporate, San Daniele del Friuli, Italy). MATERIALS AND METHODS: The Mayo Elbow Performance Score (MEPS) and elbow range of motion (ROM) were assessed. Plain radiographs were obtained to assess radiolucency in the humerus and ulna. The data were extracted from electronic patient records. RESULTS: During the follow-up period of 105.4 (range 24.6-179.9) months, 132 patients (153 elbows) underwent surgery. The cause of surgery was rheumatoid arthritis in 105 (71%) cases, posttraumatic or primary arthritis in 17 (13%) and fracture in 10 (6%) patients. The total MEPS increased on average by 35.0 points. Elbow extension deteriorated by 5.0°. Respectively, flexion improved by 10.0° and pronation by 5.0°. The difference in supination was 0.0°. Pain severity improved by 2.5 points in motion and by 5.5 points at rest. During follow-up, 24 (16%) patients needed revision surgery. The most common cause for revision was periprosthetic fracture. Radiolucent lines were seen in all zones in both the ulna and the humerus. The Kaplan-Meier survival at 5 years was 88% and 79% at 10-14 years. CONCLUSION: The Discovery® Elbow System provides good results in ROM and pain relief of the elbow. The revision rate was relatively high (16% of patients). LEVEL OF EVIDENCE: IV.
33704905 Reactivity of human labial glands in response to cevimeline treatment. 2021 Dec Among the pathologies affecting the salivary glands, the Sjögren's syndrome (SS), an autoimmune disease, causes progressive destruction of the glandular tissue. The effect of SS is particularly evident on the labial glands and the morphological analysis of these minor glands is considered useful for diagnosis. Cevimeline hydrochloride (SNI), a selective muscarinic agonist drug, is one of the elective treatments for the hyposalivation due to SS, acting not only on major salivary glands, but also on labial glands since their secretion is primarily under parasympathetic control. Aim of this study is to describe the morphology of human labial glands treated with SNI by light, transmission, and high-resolution scanning electron microscopy. Moreover, a morphometric analysis was applied to the light and transmission electron microscopy micrographs to obtain data that were then compared with analogous data collected on control and carbachol-treated labial glands. Following SNI administration, the mucous tubules exhibited enlarged lumina, which were filled with a dense mucous secretion. Occasionally, small broken debris of the cells were retrieved into the lumen. In the mucous secretory cells, some mucous droplets fused to form a large vacuole-like structure. Similarly, the seromucous acini showed both dilated lumina and canaliculi. These above reported signs of secretion were confirmed through morphometric analysis and a milder action of SNI than carbachol on labial parenchyma was observed. This study confirmed that SNI also evoked secretion on labial glands and that its effect is more physiologic than that of the pan-muscarinic agonists.
33683769 Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicen 2021 Jun AIMS: The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey. METHODS: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated. RESULTS: The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P < .05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P < .001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71). CONCLUSIONS: Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services.
33381895 Association of the Leukocyte Immunoglobulin-like Receptor A3 Gene With Neutrophil Activati 2021 Jun OBJECTIVE: Adult-onset Still's disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin-like receptor A3 (LIR-A3; gene name LILRA3) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD. METHODS: The LILRA3 deletion polymorphism and its tagging single-nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR-A3 were detected using enzyme-linked immunosorbent assay (ELISA), and the correlation between LIR-A3 plasma levels and disease activity and levels of circulating NET-DNA was investigated. LIR-A3-induced NETs were determined using PicoGreen double-stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil-like differentiated NB4 cell line transfected with LIR-B2 small interfering RNA. RESULTS: The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030-4.291], P = 0.034), and associated with leukocytosis (P = 0.039) and increased levels of circulating neutrophils (P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells (P < 0.0001) and neutrophils (P < 0.001) of LILRA3(+/+) patients. Plasma levels of LIR-A3 were elevated in patients with AOSD (P < 0.0001) and correlated with disease activity indicators and levels of circulating NET-DNA complexes. Finally, enhanced NET formation was identified in neutrophils from healthy controls and patients with inactive AOSD after stimulation of the neutrophils with LIR-A3. Moreover, NET formation was impaired in NB4 cells after knockdown of LILRB2 gene expression. CONCLUSION: Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR-A3 may play a pathogenic role by inducing formation of NETs.
33782287 The Appearance of Sjögren Syndrome on 68Ga-PSMA-11 PET/CT. 2021 Jun 1 Significant 68Ga-PSMA-11 activity is commonly observed in the lacrimal and salivary glands on PSMA PET/CT. An 80-year-old man after radical prostatectomy was evaluated with 68Ga-PSMA-11 PET/CT. There was no obvious PSMA uptake in the bilateral lacrimal, parotid, and submandibular glands. Subsequently, based on laboratory examination results and 99mTcO4 salivary gland scintigraphy, this patient was diagnosed with Sjögren syndrome, which accounted for the absence of uptake by the glands. This case showed the potential of 68Ga-PSMA-11 PET/CT in the evaluation of the lacrimal glands and major salivary glands.
34431892 Tear Lysozyme in Sjögren´s syndrome, Meibomian gland dysfunction, and non-dry-eye. 2021 PURPOSE: To evaluate the concentration of tear lysozyme in individuals with Sjogren´s syndrome, meibomian gland dysfunction, and non-dry-eye disease. METHODS: Ninety subjects were recruited for this study, including 30 with Sjogren´s syndrome, 30 with meibomian gland dysfunction, and 30 with non-dry-eye disease. All subjects were referred to participate in the study based on a "dry eye" investigation. They underwent a complete ocular surface ophthalmic examination encompassing ocular surface disease index, biomicroscopy, tear break-up time, Schirmer test type I, conjunctival vital staining with fluorescein and lissamine green, tear lysozyme concentration, and impression cytology. RESULTS: Clinical tests yielded the following results: ocular surface disease index Sjogren´s syndrome: 64.5 ± 22.6 meibomian gland dysfunction: 43.5 ± 21.4, non-dry-eye disease: 6.7 ± 4.3 (p=0.02 between groups); Schirmer I test (mm/5 min): Sjogren´s syndrome: 4.95 ± 2.25, meibomian gland dysfunction: 13.28 ± 1.53, non-dry-eye disease 13.70 ± 1.39 (p<0.01 Sjogren´s syndrome vs. non-dry-eye disease and p<0.01 meibomian gland dysfunction vs. non-dry-eye disease); tear break-up time (seconds): Sjogren´s syndrome: 3.97 ± 1.47, meibomian gland dysfunction: 3.95 ± 0.86, non-dry-eye disease: 7.25 ± 1.90 (p<0.01 Sjogren´s syndrome vs. non-dry-eye disease and p<0.01 meibomian gland dysfunction vs. non-dry-eye disease); Lissamine green score: Sjogren´s syndrome-dry-eye: 6.18 ± 2.14, meibomian gland dysfunction-dry-eye: 5.27 ± 1.27, non-dry-eye disease: 1.52 ± 0.97 (p<0.01 Sjogren´s syndrome vs. non-dry-eye disease and p<0.01 meibomian gland dysfunction vs. non-dry-eye disease); impression cytology score: Sjogren´s syndrome: 1.88 ± 0.92, meibomian gland dysfunction: 1.67 ± 0.56, non-dry-eye: 0.45 ± 0.44 (p<0.01 Sjogren´s syndrome vs. non-dry-eye disease and p<0.01 meibomian gland dysfunction vs. non-dry-eye disease) and; tear lysozyme concentration (µg/mL): Sjogren´s syndrome: 751.25 ± 244.73, meibomian gland dysfunction: 1423.67 ± 182.75, non-dry-eye disease: 1409.90 ± 188.21 (p<0.01 Sjogren´s syndrome vs. non-dry-eye disease and p<0.01 Sjogren´s syndrome vs. meibomian gland dysfunction). CONCLUSION: The concentration of lysozyme in the tears was lower in Sjögren's syndrome patients than in meibomian gland dysfunction and non-dry-eye disease groups. Hence, the lacrimal lysozyme could be considered as a simple, non-invasive, and economical biomarker to differentiate between Sjögren's syndrome dry eye disease and meibomian gland dysfunction dry eye disease.
34245687 Anti-Ro52 antibody is highly prevalent and a marker of better prognosis in patients with o 2021 Oct BACKGROUND AND AIMS: Anti-Ro52 antibody (Ab) reactivity is highly prevalent in autoimmune rheumatic diseases (ARDs), mainly Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE), but also in other inflammatory disorders. Thorough assessment of the prevalence, clinical significance and epitope specificity of Ro52-autoAbs in cancerous diseases is still lacking. MATERIAL AND METHODS: Anti-Ro52 Ab reactivity was tested in a large cohort of 490 patients with various malignant diseases. Ro52-autoAb epitope mapping by an in house line immunoassay was carried out using 5 recombinant Ro52 polypeptides spanning Ro52. RESULTS: Anti-Ro52 abs were significantly more prevalent in patients with ovarian cancer (30%) compared to patients with 6 other malignant diseases (median 8.1%, range 5.9-15.8%). The presence of anti-Ro52 abs in patients with ovarian cancer was strongly associated with better overall survival. Ro52 epitope mapping of patients with ovarian cancer was dissimilar to that of SLE and SjS ARDs, less frequently recognizing Ro52-1 and Ro52-4 fragments compared to patients with SLE and SjS. CONCLUSION: We demonstrate for first time an unexpectedly high frequency of anti-Ro52 abs in patients with ovarian cancer, their presence indicating better overall survival. Their distinguishing epitope profile may suggest a non-SLE or SjS-related stimulus for autoAb production.
33970381 Efficacy of tight control strategy in the treatment of adult-onset Still disease. 2021 Oct BACKGROUND: Adult-onset Still's disease (AOSD) characterized by a high spiking fever, skin rash, arthritis, and leukocytosis. The aim of the present study was considering the long-term outcomes of patients with AOSD who were treated with tight control strategy with disease modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-six patients with AOSD treated with tight control strategy were included. Four levels of remission were defined. Remission on-treatment was defined as the clinical remission, patient global assessment (PGA) ≤ 1, and prednisolone dose ≤ 5 mg/day for at least 6 months. Remission off-treatment was defined as the clinical remission and PGA ≤ 1 for at least 6 months as well as discontinuation of prednisolone, DMARDs, and biologics. Sustained remission on-treatment was defined as the clinical remission, PGA ≤ 1, and prednisolone dose ≤ 5 mg/day for ≥ 5 years. Sustained remission off-treatment was defined as the clinical remission and PGA ≤ 1 for ≥ 5 years as well as discontinuation of prednisolone, DMARDs, and biologics. RESULTS: Throughout a median follow-up of 47 months, remission on-treatment and off-treatment were obtained in 94.6% and 44.6% of patients, respectively. Sustained remission on-treatment and off-treatment were obtained in 79.2 and 8.3% of patients, respectively. Glucocorticoids (GCs) and DMARDs were discontinued in 66.1% and 48.2% of the patients, respectively. Apart from the older age of the patients in the on-GCs group, no significant differences were observed between the groups. CONCLUSION: Our study showed that using DMARDs with tight control strategy at the presentation of AOSD may control disease activity successfully. Key Points • Using DMARDs with tight control strategy at the presentation of adult-onset Still's disease may control disease activity successfully.