Browse

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

ID PMID Title PublicationDate abstract
34306188 ZFAS1 knockdown inhibits fibroblast-like synoviocyte proliferation, migration, invasion a 2021 Sep Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by joint disorders. Long non-coding RNA zinc finger antisense 1 (ZFAS1) is aberrantly expressed in numerous human diseases, including RA. The present study aimed to investigate the functions and underlying mechanisms of ZFAS1 in RA. Reverse transcription-quantitative PCR was performed to determine the expression levels of ZFAS1, microRNA (miR)-3926 and follistatin-like protein 1 (FSTL1). MTT assay, flow cytometric analysis and Transwell assay were performed to examine the proliferation, apoptosis, migration and invasion of fibroblast-like synoviocytes (FLSs), respectively. Western blotting was employed to measure the protein expression levels of cleaved caspase-3, interleukin (IL)-6, IL-1β, tumor necrosis factor-α and FSTL1. Dual-luciferase reporter assay was performed to verify the interaction between miR-3926 and ZFAS1 or FSTL1. The results demonstrated that ZFAS1 and FSTL1 were upregulated, and miR-3926 was downregulated in RA synovial tissues and RA-FLSs. ZFAS1 knockdown suppressed cell proliferation, migration, invasion and inflammatory cytokine production, and induced apoptosis in RA-FLSs. ZFAS1 acted as a sponge for miR-3926, and ZFAS1 overexpression abolished the impact of miR-3926 on the development of RA-FLSs. FSTL1 was a direct target of miR-3926, and the effect of FSTL1 knockdown on the progression of RA-FLSs was rescued by miR-3926 inhibition. Furthermore, ZFAS1 regulated FSTL1 expression levels via sponging miR-3926 in RA-FLSs. In conclusion, ZFAS1 knockdown inhibited RA-FLS proliferation, migration, invasion and inflammatory cytokine production, and induced apoptosis in RA via the miR-3926/FSTL1 axis.
34268230 Single nucleotide polymorphism rs5029937 in TNFAIP3 gene is correlated with risk of rheuma 2021 Background: Rheumatoid arthritis (RA) is a progressive and common autoimmune disease with multifactorial etiology. Several pieces of research show that genetic factors play a major role in the incidence of RA. Several genome-wide association studies (GWAS) have identified the tumor necrosis factor alpha inducible protein 3 (TNFAIP3) genes as one of the candidate loci. The TNFAIP3 gene encoding ubiquitin-editing protein A20 witch restricts B cell survival and prevents autoimmunity. Previous studies have indicated that single nucleotide polymorphisms (SNPs) in the TNFAIP3 gene are correlated with several autoimmune disorders. In the present study, we assessed the possible association between SNP rs5029937 (intronic variant) in the TNFAIP3 gene with RA risk in the Iranian population. Methods: A case-control study using 50 RA patients and 50 control subjects was undertaken to evaluate rs5029937 (G>T) genotypes using real-time PCR high resolution melting method (HRM). The SPSS22 was used for statistical analyses and the significance level was set at P<0.05. Results: Logistic regression analysis demonstrates that homozygous TT + heterozygous TG genotypes compared with GG genotype increase the risk of RA (TT+TG vs GG; P= 0.004, OR= 3.46; 95%CI [1.492-8.075]). Also, individuals with allele T were more frequently affected with RA than subjects with G allele (T vs G; P= 0.004, OR= 2.61; 95%CI [1.382-4.919]). Conclusion: Our findings propose a substantial correlation between rs5029937 (G>T) polymorphism and RA risk in Iranian population.
34195135 Evaluation of levels of oxidative stress as a potential biomarker in patients with rheumat 2021 May OBJECTIVES: One of the most prevalent autoimmune disease globally, rheumatoid arthritis (RA) is caused by interplay of multiple inflammatory mediators in specific joints. Altered redox balance is one of the key factors in pathophysiology of RA. This study aims to find whether oxidative stress in peripheral blood neutrophil correlates with the disease activity and disability associated with it. METHODS: Ten healthy controls and 29 RA patients with moderate to severe disease activity (DAS28 score >3.2) were recruited and reactive oxygen species (ROS) level in peripheral blood neutrophil was measured using flow cytometry at baseline visit and after 6 months follow-up. Functional status of RA patients was measured using Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: RA patients showed significantly higher level of ROS in compared to healthy control. DAS28 correlated well with ROS at baseline visit (Pearson's r = +0.63) as well as follow-up visit (Pearson's r = +0.75). HAQ-DI showed weak positive correlation at baseline visit (Pearson's r = 0.1) but it was negative at follow-up visit (Pearson's r = -0.19). CONCLUSIONS: Oxidative stress mirrors the disease activity in RA and can be considered as a biomarker, but it is not related with functional ability of the patients.
34093746 Treatment expectations as a possible prognostic factor for DMARD response in rheumatoid ar 2021 BACKGROUND: The prediction of the individual's response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is challenging and often limited. Here we evaluated the influence of patients' expectations towards a change in treatment with DMARD on clinical outcome in RA. METHODS: One hundred patients (74 female) with RA (2010 ACR/EULAR classification criteria) and an upcoming change in DMARD treatment due to non-response or adverse effects were included. Patients' treatment beliefs, health-related quality of life and treatment expectations were measured using the Beliefs about Medicines Questionnaire (BMQ), the Short Form 36, and self-designed questions about expectations before treatment initiation (T0), and DAS28-CRP was calculated at T0 and after 4 months (T4). Associations between patients' beliefs and expectations and changes in DAS28-CRP (T0 to T4, ΔDAS28-CRP) were explored by regression analyses after multiple imputation. RESULTS: A total of 99 patients were included, of whom 84 completed all questionnaires. Thirty-six percent of all variability in treatment response (ΔDAS28-CRP) was explained by expectations assessed with the questionnaires and the C-reactive protein (CRP)-value at T0. Among these, the expected improvement rate, with 10.5%, as well as the CRP-value at T0, with 10.6%, had the greatest positive effect whereas the fear of adverse effects, with 11.4%, and the BMQ.concern scale, with 9.0%, had the greatest negative impact on ΔDAS28. CONCLUSION: Patients' expectations towards newly induced DMARD therapies influence clinical response and may serve as possible explanatory factors for treatment response affecting subjective and objective outcome parameters. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00017005.
33921836 Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activatio 2021 Apr 19 Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators-the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker-C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA.
33796022 Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal 2021 Rheumatoid arthritis (RA) acts as one of the most common, agnogenic and chronic inflammatory-autoimmune disorder which is characterized by persistent synovitis, cartilage destruction, and joint deformities, leads to a wide range of disabilities, and increased mortality, thus imposing enormous burdens. Several drugs with anti-inflammatory and immunomodulatory properties such as celecoxib, diclofenac and methotrexate are being selected as conventional drugs in the allopathic system of medicine for the treatment of RA in clinic. However, there are some serious side effects more or less when using these drugs because of their short poor bioavailability and biological half-life for a long time. These shortcomings greatly promote the exploration and application of new low- or no-toxicity drugs for treating the RA. Meanwhile, a growing number of studies demonstrate that several herbs present certain anti-inflammatory and anti-arthritic activities through different enzymes and their derivatives, which indicate that they are promising therapeutic strategies when targeting these mediators based on herbal medicinal products in RA research. This review article summarizes the roles of the main enzymes and their derivatives during the pathogenesis of RA, and clearly clarifies the explicit and potential targeted actions of herbal medicinal products that have anti-RA activity. Our review provides timely and critical reference for the scientific rationale use of herbal medicinal products, with the increasing basic research and clinical application of herbal medicinal products by patients with RA.
33783764 Outcome of a metaphyseal reverse total shoulder replacement in rheumatoid arthritis. 2021 Mar 30 AIM: To assess the clinical and radiological results of a metaphyseal reverse total shoulder arthroplasty (rTSA) without diaphyseal stem, in rheumatoid arthritis (RA) patients. METHODS: Forty-five shoulders in 36 consecutive RA patients (2005-2015) underwent rTSA with a bone impaction technique. Patients were assessed clinically and radiographically preoperatively, at 3 weeks, 3 months, 6 months, 12 months post-operatively, and yearly thereafter, using constant score (CS), pain score, subjective shoulder value (SSV) and patient satisfaction score. RESULTS: Forty-four shoulders with mean follow-up of 67 months (range 24 m-146 m (12y)) were available for follow-up. Mean age at surgery was 68.7 years (range 39-86). CS improved from 17.5 ± 10.5(SD) (age/sex adjusted 23.9 ± 14.5(SD)) preoperatively to 60.9 ± 17.4 (SD) (age/sex adjusted 86.5 ± 24.5 (SD)) at last follow-up (P < 0.001). Pain score and SSV also significantly improved (p < 0.001). Mean range of movement improved to 140°active forward flexion, 134°active abduction, 47°active external rotation (AER) and 70°active internal rotation (AIR). The results were maintained over time. Combined early and late complication rate was 15.6%, which is lower than described in the literature for RA. No lucencies, loosening, subsidence or stress shielding were evident radiographically. CONCLUSION: Metaphyseal rTSA without a diaphyseal stem is successful and safe in RA patients. Patients achieve good function and have high satisfaction rates. LEVEL OF EVIDENCE: Case series: Level IV.
33478279 New frontiers in precision medicine for Sjogren's syndrome. 2021 Feb Introduction: Sjögren's syndrome is a unique systemic autoimmune disease, placed in the center of systemic autoimmunity and at the crossroads of autoimmunity and lymphoproliferation. The diverse clinical picture of the disease, the inefficacy of current biologic treatments, and the co-existence with lymphoma conferring to the patients' morbidity and mortality force the scientific community to review disease pathogenesis and reveal the major implicated cellular and molecular elements.Areas covered: Biomarkers for early diagnosis, prediction, stratification, monitoring, and targeted treatments can serve as a tool to interlink and switch from the clinical phenotyping of the disease into a more sophisticated classification based on the underlying critical molecular pathways and endotypes. Such a transition may define the establishment of the so-called precision medicine era in which patients' management will be based on grouping according to pathogenetically related biomarkers. In the current work, literature on Sjogren's syndrome covering several research fields including clinical, translational, and basic research has been reviewed.Expert opinion: The perspectives of clinical and translational research are anticipated to define phenotypic clustering of high-risk pSS patients and link the clinical picture of the disease with fundamental molecular mechanisms and molecules implicated in pathogenesis.
32407572 Illness Experiences of Chilean Women With Sjögren's Syndrome: The Patient Perspective. 2021 Aug OBJECTIVE: Sjögren's syndrome (SS) challenges everyday functioning and well-being. The aim of this study was to structure and summarize the life experiences of Chilean women with SS in an integrated model. METHODS: Interviews from a previous study yielded 75 experiences of living with SS. A sample of 30 women with SS sorted these experiences by content and rated their level of agreement with each experience. A hierarchical cluster analysis was used to structure the experiences of the participants with SS in a comprehensive overview. A team-based consensus analysis was used to define the number of clusters. The level of agreement was examined with Wilcoxon's signed rank test. RESULTS: Ten clusters were identified and grouped into 6 main categories: symptoms (clusters: mucosal dryness and related symptoms), social environment, emotion management (clusters: fears and sadness), information (clusters: uncertainty and lack of knowledge), coping strategy (clusters: resilience and self-care), and health staff relationship. The clusters that describe the more common experiences among patients were resilience, self-care, uncertainty, lack of knowledge, health staff relationship, and mucosal dryness. CONCLUSION: This study provided an integrated and structured overview of disease experiences comprising both biomedical and psychosocial aspects as being of vital importance for the health of patients with SS. The overview can be used to get a quick impression of disease experiences that are important for an individual patient, in a therapeutic goal setting, and in the construction and evaluation of medical and nonmedical interventions or education.
34874832 Practical guidelines for the early diagnosis of Sjögren's syndrome in primary healthcare. 2021 Nov Primary care physicians can play a crucial role by recognising Sjögren's syndrome (SS) in the early stages identifying those patients with the greatest probability of being diagnosed with SS. SS has a very specific epidemiological profile at presentation (female aged 30-50 years), which may aid an early diagnosis. Although the disease may be expressed in many guises, there are three predominant clinical presentations that should be considered as key clues to increased clinical suspicion (multiple symptoms of dryness, asthenia-polyalgia syndrome and systemic organ-specific manifestations). The physical examination may provide important clues to systemic involvement (parotid gland enlargement, skin lesions suggestive of purpura or annular erythema, respiratory crackles, arthritis, neurological sensory or motor deficits). Simple laboratory studies may be very useful in reinforcing the clinical suspicion of SS, and the triad of cytopenia, raised erythrocyte sedimentation rate and high serum gamma globulin levels is a very specific "biological" pattern suggesting SS. A solid clinical suspicion of SS requires both the patient reporting sicca symptoms and objective evidence that these symptoms are associated with dysfunction of the lachrymal and salivary glands. Ultrasonography of the parotid glands, a non-invasive method, may be a major advance in the diagnostic approach to SS in primary care. Primary care physicians must be considered essential members of the multidisciplinary team in charge of the follow-up of SS patients, due to their key role in the continuum of patient care and their cross-sectional knowledge of common diseases that frequently coexist in patients with SS.
33886458 COVID-19 shares clinical features with anti-melanoma differentiation-associated protein 5 2021 May OBJECTIVES: To investigate the similarities and differences between Coronavirus disease 2019 (COVID-19) and autoimmune and autoinflammatory rheumatic diseases characterised by hyperferritinaemia, such as antimelanoma differentiation-associated protein 5 (MDA5) autoantibody-positive dermatomyositis and adult Still's disease. METHODS: We reviewed consecutive, newly diagnosed, untreated patients with COVID-19, anti-MDA5 dermatomyositis, or adult Still's disease. We compared their clinical, laboratory, and radiological characteristics, including the prevalence of macrophage activation syndrome and lung involvement in each disease. RESULTS: The numbers of patients with COVID-19, anti-MDA5 dermatomyositis, and adult-onset Still's disease with hyperferritinaemia (serum ferritin ≥500ng/dL) who were included for main analysis were 22, 14, and 59, respectively. COVID-19 and adult Still's disease both featured hyperinflammatory status, such as high fever and elevated serum C-reactive protein, whereas COVID-19 and anti-MDA5 dermatomyositis both presented with severe interstitial lung disease and hypoxaemia. While two-thirds of the patients in each group met the criteria for macrophage-activated syndrome that is used in systemic juvenile idiopathic arthritis, the HScore, an indicator of haemophagocytic lymphohistiocytosis, was low in anti-MDA5 dermatomyositis and COVID-19 even in severe or critical cases. The findings of chest computed tomography were similar between COVID-19 and anti-MDA5 dermatomyositis. CONCLUSIONS: COVID-19 shared clinical features with rheumatic diseases characterised by hyperferritinaemia, including anti-MDA5 dermatomyositis and adult Still's disease. These findings should be investigated further in order to shed light on the pathogenesis of not only COVID-19 but also the aforementioned rheumatic diseases.
34933686 Association of lifestyle and disease characteristics with self-rated wellness/health score 2021 Dec 22 OBJECTIVE: To study the relationship of self-rated wellness/health and lifestyle in patients with rheumatoid arthritis. METHODS: Self-rated wellness/health, demographics, smoking, mood, sleep, physical activity, diet, symptoms/signs, body mass index and laboratory findings in 142 patients with rheumatoid arthritis were collected in the current cross-sectional study. Multivariable generalized additive model (GAM) was employed to study the association of self-rated wellness/health score and lifestyle factors. RESULTS: Female/male ratio was 116/26 and the mean (SD) age of sample was 52 (13) years. Mean (SD) self-rated wellness/health score out of 10 was 7.2 (1.63). Mean (SD) number of tender joints and swollen joints were 4.42 (4.55) and 4.00 (4.26), respectively. The mean sleep score was 29.5 out of 70. Patients went to bed more than one hour earlier during the weekdays compared to weekends (22:45 vs. 23:52 PM, respectively, p < 0.0001). They also woke up more than one hour earlier during the weekdays compared to the weekends (6:08 vs. 7:20 AM, respectively, p < 0.0001). Their nap duration during weekdays was about half an hour shorter than the nap duration on weekends (19.75 vs. 48.02 minutes, respectively, p < 0.0001). The mean mood and diet scores were 18.5/35 and 22.5/42, respectively. By backward elimination in multivariable regression model (GAM), disease duration, mood, sleep quality, weekdays sleep characteristics (sleep duration, time to go to bed, wake-up time, time to fall asleep and nap duration), and sleep duration on weekends remained in the final model (R(2) = 0.225, p = 0.01). Sleep quality, nap duration on weekdays, night sleep duration on weekends and mood status were the significant variables associated with self-rated wellness/health score. CONCLUSION: In patients with rheumatoid arthritis, the low self-rated wellness/health score was associated with the low sleep quality, long sleep duration on weekends, and long nap duration on weekdays.
34636022 Impact of smoking habit on adult-onset Still's disease prognosis, findings from a multicen 2022 Mar The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still's disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45-14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46-15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43-11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36-11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33-13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis. Key points • Smoking habit resulted to be a negative prognostic factor on AOSD. • Smokers were characterised by an increased frequency of serositis and higher values of systemic score. • Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.
34321337 Childhood-Onset Sjögren Syndrome Presenting as Pulmonary Hemorrhage. 2021 Aug Primary Sjögren syndrome is an autoimmune disease characterized by inflammation of the salivary and lacrimal exocrine glands but can also present with systemic extraglandular manifestations, including pulmonary disease. Commonly described pulmonary manifestations of Sjögren syndrome include airway disease, interstitial lung disease, pulmonary arterial hypertension, and lymphoproliferative disorders. However, diffuse alveolar hemorrhage as a sequela of Sjögren syndrome has rarely been described in the adult literature and has never been described in a child. Here we report the case of an 11-year-old girl who presented with diffuse alveolar hemorrhage and was diagnosed with childhood-onset Sjögren syndrome who otherwise lacked typical clinical features, such as sicca symptoms, at the time of presentation. She was successfully treated with corticosteroids and rituximab, with sustained pulmonary remission 1 year post diagnosis. Our case highlights the heterogenous presentation of Sjögren syndrome in the pediatric population and the need for increased awareness among pediatric providers to recognize potential systemic manifestations of this disease to avoid delayed diagnosis.
34251315 Clinical characteristics of macrophage activation syndrome in adult-onset Still's disease. 2021 Sep OBJECTIVES: Macrophage activation syndrome (MAS) is considered the most severe complication of adult-onset Still's disease (AOSD). This retrospective observational study was conducted to explore the clinical characteristics of AOSD-MAS patients, the risk factors for MAS in AOSD and prognostic factors in AOSD. Early changes in the clinical characteristics of AOSD-MAS were also studied. METHODS: 111 hospitalised AOSD patients were included in this retrospective analysis and analysed for the features of AOSD-MAS, selecting independent risk factors associated with MAS and the correlations between clinical characteristics and patient survival. RESULTS: Nine subjects (8.1%) developed MAS. AOSD-MAS patients had a higher incidence of jaundice (33.3% vs. 2.9%, p=0.007) and aspartate aminotransferase (AST) greater than 5-fold (33.3% vs. 2.9%, p=0.007). Jaundice was associated with an increased risk of MAS (OR=16.50, 95% CI: 2.73-99.82, p=0.002). The AOSD-MAS group had a higher mortality rate (55.6% vs. 8.0%, p=0.001). MAS (HR=11.22, 95% CI: 3.46-36.38, p<0.001), and white blood cell (WBC) greater than 20 109/L (HR=5.80, 95% CI: 1.09-30.92, p=0.040) were independent prognostic factors for death in AOSD patients. In the AOSD-MAS group, transaminase, triglycerides (TGs) and serum ferritin (SF) were elevated in the early disease stage, sometimes earlier than changes in blood cells in MAS. CONCLUSIONS: MAS occurrence significantly reduced the survival rate of patients with AOSD. The presence of jaundice was associated with MAS occurrence. MAS and a WBC count >20 109/L were associated with a high risk of AOSD-related death. AOSD should alert the possibility of MAS when elevated transaminase, TGs and SF cannot be explained.
33822710 Factors associated with delayed diagnosis of Sjögren's syndrome among members of the Japa 2021 Nov OBJECTIVES: The heterogeneous nature of the signs and symptoms of Sjögren's syndrome (SS) often causes delays in diagnosis. The reasons for these delays have not been investigated in Japan and need to be determined. METHODS: We conducted a questionnaire survey of members of the Japanese Sjögren's Association for Patients (JSAP). Questionnaire items were demographic (sex, age at diagnosis and current age) and factors associated with delayed diagnosis (age at first visit to hospital or clinic, medical department first attended, and initial symptoms). Patients were classified into those diagnosed in <1 year and those diagnosed in ≥1 year. RESULTS: Of the 510 patients questioned, 276 returned the questionnaire, and 255 questionnaires were assessed. The average time to diagnosis was 3.47 years. After adjustment, risk factors for delayed diagnosis were initial visit to an internal medicine department [adjusted odds ratio (aOR) 3.13, 95% confidence interval (CI) 1.42-6.92] or ophthalmology department (aOR, 2.63, 95% CI 1.07-6.50), younger age at initial visit to hospital or clinic (aOR, 0.96, 95% CI 0.94-0.99), and having symptoms of only dry eye (aOR, 2.69, 95% CI 1.09-6.64). Diagnosis was faster when patients had a dry mouth (aOR, 0.55, 95% CI 0.30-1.00) or cutaneous symptoms (aOR, 0.29, 95% CI 0.11-0.82). CONCLUSIONS: Risk factors for delayed SS diagnosis were younger age, initial visit to internal medicine or ophthalmology department, and having only dry eye. We need to raise awareness of SS among doctors and the general public to improve early diagnosis and therapeutic potential.
33833871 New Studies of Pathogenesis of Rheumatoid Arthritis with Collagen-Induced and Collagen Ant 2021 Much public research suggests that autoimmune diseases such as rheumatoid arthritis (RA) are induced by aberrant "self" immune responses attacking autologous tissues and organ components. However, recent studies have reported that autoimmune diseases may be triggered by dysbiotic composition changes of the intestinal bacteria and an imbalance between these bacteria and intestinal immune systems. However, there are a few solid concepts or methods to study the putative involvement and relationship of these inner environmental factors in RA pathogenesis. Fortunately, Collagen-Induced Arthritis (CIA) and Collagen Antibody-Induced Arthritis (CAIA) models have been widely used as animal models for studying the pathogenesis of RA. In addition to RA, these models can be extensively used as animal models for studying complicated hypotheses in many diseases. In this review, we introduce some basic information about the CIA and CAIA models as well as how to apply these models effectively to investigate relationships between the pathogenesis of autoimmune diseases, especially RA, and the dysbiosis of intestinal bacterial flora.
35087513 High Dimensional Analyses of Circulating Immune Cells in Psoriatic Arthritis Detects Eleva 2021 Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, affecting up to 40% of patients with psoriasis. Constitutive expression by CD4+ T cells of an active form of STAT3, a signal transducer and transcription factor, has been shown to induce many of the major features of PsA in an animal model. We used high dimensional mass cytometry (CyTOF) to probe ex-vivo levels of phosphorylated STAT3 (pSTAT3) in circulating immune cell subpopulations from PsA patients during active and inactive states. We evaluated the frequency of 16 immune cell populations and the levels of the activated forms of STAT3 (pSTAT3) and, for comparison, STAT1 (pSTAT1) and Src (pSrc) in whole blood fixed shortly after collection. In addition to PsA patients, we studied active rheumatoid arthritis (RA) patients. Increased levels of pSTAT3 were found in all the CD4+ T cell subsets analyzed, specifically, Th1, Th2, Th17, T follicular helper (Tfh) and T regulatory (Treg) as well as in CD14+CD16- (classical) monocytes from active PsA patients compared to inactive patients. After correcting for body mass index (BMI), smoking and conventional disease modifying antirheumatic drugs (c-DMARDs), levels of pSTAT3 levels remained increased in Th1 and Tfh CD4+ T cells, and in CD14+CD16- monocytes from active patients compared to inactive patients. No differences between the patient groups were observed for pSTAT1 or pSrc. No differences were found between the active PsA and active RA groups after correction for multiple testing. During active PsA, circulating Th1 and Tfh CD4+ T cells, and CD14+CD16- monocytes expressing high levels of pSTAT3 may play a role in PsA pathophysiology, perhaps by migration to inflamed sites.
34224070 Pharmacological support to anti-arthritic prospective of physostigmine: a new approach. 2021 Aug Rheumatoid arthritis (RA) is a slowly progressing inflammatory autoimmune disease. Several features are involved in the RA pathogenesis in addition to environmental and genetic factors. Previously it has been reported that acetyl cholinesterase (AChE) activity is enhanced in old age and may contribute in the progression of RA. The current experimental work was projected to assess the activity of physostigmine (a cholinesterase inhibitor) for treatment of RA. In vitro and in vivo approaches were used for such evaluation. However, enzyme linked immunosorbent assays (ELISA) was performed to determine the concentrations of Prostaglandins E2 (PGE2) and tumor necrosis factor-α in arthritic rats after treatment with physostigmine. Moreover, anti-oxidant assays were employed to calculate the level of super oxide dismutase (SOD) and catalase peroxidase (CAT) in tissue of treated animals. The results claimed the dose dependent protective and stabilizing effect of physostigmine on denaturation of albumin (egg and bovine serum) protein and human red blood cell membrane, respectively, through in vitro studies. Furthermore, the physostigmine (10 and 20 mg/kg) significantly (p < 0.001) reduced the swelling of paw after induction of arthritis with formaldehyde or complete Freund's adjuvant (CFA) as compared to arthritic control animals. Moreover, significant (p < 0.001) reduction in the levels of inflammatory markers (PGE2 and TNF-α) at doses of 10 and 20 mg/kg of physostigmine has been observed in ELISA test. Likewise, there was a prominent rise in levels of SOD and CAT in animals treated with physostigmine. These findings pharmacologically conclude the anti-arthritic effect of physostigmine.
33397417 The burden of depressive disorders in musculoskeletal diseases: is there an association be 2021 Jan 4 IMPORTANCE: Evidence emerged concerning how inflammatory arthritis and mood disorders can often occur in the same patient and show a similar clinical pattern. An overview of the rheumatological and psychiatric aspects of these diseases can certainly be useful for the improvement of patients' clinical and therapeutic management. OBJECTIVE: The aim of this narrative review was to summarize existing literature about common pathogenetic and clinical aspects as a means of improving management and therapeutic approach in patients affected by rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. Outcomes such as disease activity indexes and patient reported outcomes (PROs) were considered. FINDINGS: Common pathogenetic pathways emerged between inflammatory arthritis and mood disorders. Pro-inflammatory mechanisms, such as TNFα, IL-6, IL-17 and oxidative stress factors as well as neurotransmitter alterations at the level of CNS and blood-brain barrier (BBB) cells are involved. The activation of these common pathogenetic pathways is, also, affected by the same triggers, such as smoking, stress, lifestyle, and evidence has emerged concerning the possibility of the clinical efficacy of using the same therapeutic approaches. CONCLUSIONS: The main causes of the variability in clinical studies outcomes are the rheumatological diseases considered, the prevalence of depression in the general population and in patients with rheumatological diseases and the type of depressive symptom examined. Patients affected by inflammatory arthritis can present symptoms and signs in common with mood disorders, leading to possible clinical overlap. There are still few studies analyzing this concept: they are extremely heterogeneous, both in the characteristics of the population taken into consideration and in the methods used for the definition of depressive disorder, but the suggestions of the data obtained so far are promising and deserve to be pursued.