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ID PMID Title PublicationDate abstract
35033752 Role of Suppressor of cytokine signaling 2 during the development and resolution of an exp 2022 Feb Rheumatoid arthritis(RA) is a debilitating chronic inflammatory disease. Suppressors of Cytokine Signaling(SOCS) proteins regulate homeostasis and pathogenesis in several diseases. The intersection between RA pathophysiology and SOCS2 is unclear. Herein, we investigated the roles of SOCS2 during the development of an experimental antigen-induced arthritis(AIA). In wild type mice, joint SOCS2 expression was reduced during AIA development. At the peak of inflammation, SOCS2(-/-) mice presented with reduced numbers of infiltrated cells in their joints. At the late phase of AIA, however, exhibited increased adhesion/infiltration of neutrophils, macrophages, CD4(+)-T cells, CD4(+)CD8(+)-T cells, and CD4(-)CD8(-)-T cells associated with elevated IL-17 and IFN-γ levels, joint damage, proteoglycan loss, and nociception. SOCS2 deficiency resulted in lower numbers of apoptotic neutrophils and reduced efferocytosis. The present study demonstrated the vital role of SOCS2 during the development and resolution of an experimental RA model. Hence, this protein may be a novel therapeutic target for this disorder.
35198304 Epicardial Fat Thickness: A Cardiometabolic Risk Marker in Rheumatoid Arthritis. 2022 Jan BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology which mainly involves synovial joints. However, the corresponding systemic inflammation may result in disorders of multiple other organ systems. Several organs and organ systems are potentially involved in RA, particularly in severe diseases. The organs most involved are the lung, heart, eyes, and nervous system. Extra-articular manifestations of RA may develop even before the onset of arthritis. Emerging epidemiological evidence shows that cardiovascular disease (CVD) accounts for near about 50% of RA-associated death. Epicardial fat thickness (EFT) has recently emerged as a new marker of cardiometabolic risk. Although Epicardial fat (EF) is needed for heart muscle function, given its intrinsic inflammatory status, EFT displays the potential to serve as a therapeutic target in patients with RA. OBJECTIVES: To evaluate EFT using echocardiography in RA patients compared to age and sex-matched control and to find the factors associated with EFT in RA patients. MATERIALS AND METHODS:  This current study was conducted in the Department of Medicine, Postgraduate Institute of Medical Education & Research. The study was conducted from November 2016 to March 2018. Patients with BMI ≥ 30 kg/m(2), diabetes mellitus, primary hyperlipidemia, and uncontrolled hypertension were particularly excluded. Thirty patients of age and sex-matched controls were also taken for the study. All the patients and controls selected for the study were subjected to detailed history taking and clinical examination. They were subjected to lab investigations and echocardiography. The 30 RA patients included in the study were diagnosed according to the 2010 ACR-EULAR criteria. Disease activity was measured by the disease activity score (DAS28) index. RESULTS:  Group 1 included 30 patients with RA and group 2 included 30 age and sex-matched controls. Pearson correlation analysis was done between EFT and other variables. Only HDL, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hS-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), DAS28, and disease duration were found to have a significant correlation with EFT. CONCLUSION:  In patients with RA, EFT, left ventricular mass, and diastolic dysfunction are increased in RA patients compared to healthy controls. Out of the conventional CVD risk factors, only HDL was associated with increased EFT in RA patients. In RA patients, DAS28, disease duration, RF, anti-CCP, and markers of inflammation (ESR, hs-CRP) were also associated with increased EFT.
35314903 Serum Uric Acid as a Diagnostic Biomarker for Rheumatoid Arthritis-Associated Interstitial 2022 Mar 22 Previous studies have suggested a correlation between uric acid (UA) and lung lesion in some diseases. However, it remains unknown whether UA contributes to the lung injury in rheumatoid arthritis (RA). Our study aimed to investigate the clinical value of the UA level in the severity of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We measured UA in serum and bronchoalveolar lavage fluid (BALF), and UA levels of subjects were compared. As for the role of UA on ILD, we incubated A549 cells with UA and the expression of EMT markers was measured by immunofluorescence staining. The concentrations and messenger RNA expression of IL-1, IL-6, and transforming growth factor-β (TGF-β) were measured by ELISA and RT-PCR, respectively. We observed that serum UA levels in RA were significantly higher than those in controls. And, higher UA was measured in both serum and BALF of patients with RA-ILD, particularly those with interstitial pneumonia (UIP) pattern. Additionally, the correlation of the serum and BALF UA levels with serum KL-6, a biomarker of ILDs, in RA was significant (r = 0.44, p < 0.01; r = 0.43, p < 0.01). And, the negative correlations of UA, in both serum and BALF, with forced vital capacity (r =  -0.61, p < 0.01; r =  -0.34, p < 0.01) and diffusing capacity for carbon monoxide (r =  -0.43, p < 0.01; r =  -0.30, p < 0.01) were measured in patients. In the ROC curve analysis, the AUC value of UA for RA-ILD was 0.744 (95% CI: 0.69-0.80; p < 0.01), and the AUC of serum UA for predicting UIP pattern of patients with RA-ILD was 0.845 (95% CI: 0.78-0.91; p < 0.01), which showed the significance of the UA in clinical settings. Also, the in vitro experiment showed that UA induced epithelial-to-mesenchymal transition (EMT) and production of IL-1, IL-6, and TGF-β in A549 cells. Therefore, the elevated UA levels may be a diagnostic marker in RA-ILD, particularly RA-UIP.
35174462 The Role of Shared Epitope in Rheumatoid Arthritis Prognosis in Relation to Anti-Citrullin 2022 Apr INTRODUCTION: Shared epitope (SE) is present in high proportions of anti-citrullinated protein antibody (ACPA) + patients with rheumatoid arthritis (RA) and is associated with poor prognosis. We assessed the role of SE in RA prognosis, in relation to ACPA positivity. METHODS: Patients enrolled in the Brigham and Women's RA Sequential Study were included. Changes from baseline in disease activity (Disease Activity Score in 28 joints using C-reactive protein [DAS28 (CRP)], Clinical Disease Activity Index [CDAI], Simplified Disease Activity Index [SDAI]) to 1 year were assessed. Baseline characteristics were compared by SE and ACPA status (±; chi-squared, Kruskal-Wallis). Association between number of SE alleles and ACPA status (logistic regression models), relationships between baseline characteristics and changes in disease activity (adjusted linear regression model), and effect of ACPA on the association between SE and changes in disease activity (mediation analysis) were studied. RESULTS: Nine hundred twenty-six patients were included. SE + versus SE - patients had significantly longer disease duration and higher disease activity scores and were more likely to have erosive disease, have higher comorbidity burden, and be RF + (all p < 0.05). Among patients with one or two SE alleles (vs. 0), odds of being ACPA + were 1.97 (p = 0.0003) and 3.82 (p < 0.0001), respectively. SE + versus SE - patients had worse disease activity scores as indicated by mean increases in DAS28 (CRP) of 0.22, CDAI of 2.07, and SDAI of 2.43 over 1 year (all p < 0.05). Direct effect of SE + accounted for 76.4-80.1% of total effect in disease activity increases. CONCLUSIONS: SE is strongly associated with ACPA positivity and higher disease activity in patients with RA. SE was associated with greater increases in disease activity over 1 year, which was partially mediated by the presence of ACPA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01793103; registration date: February 15, 2013, retrospectively registered.
35326903 Association between Rheumatoid Arthritis and Poor Self-Perceived Oral Health in Korean Adu 2022 Feb 24 BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) and oral health problems have been reported as specific disease units; however, this study was conducted to evaluate the association between RA and comprehensive oral health status. Therefore, this study aimed to assess the association between RA and oral health using self-perceived oral health (SPOH) variables that can determine the oral health status in Korean adults using representative national data. METHODS: Data from 40,186 selected participants were collected from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2007 and 2018. The prevalence relative risk (PRR) was estimated using Poisson regression analysis to obtain the risk ratio of the SPOH according to RA. RESULTS: The risk of SPOH depending on the RA status was statistically significant (odds ratio [OR] = 1.108, 95% confidence interval [CI] 1.005-1.222). In addition, the risk of SPOH depending on the RA status was higher in the group with diabetes mellitus (DM) (OR = 1.205, 95% CI 0.966-1.503) than in the group without DM (OR = 1.088, 95% CI 0.976-1.214). CONCLUSIONS: In this study, a significant association was identified between RA and SPOH. Oral health experts should identify the factors affecting the oral health of patients with RA and provide correct oral health care; however, additional research is needed.
35449236 Perspectives on applying immuno-autonomics to rheumatoid arthritis: results from an online 2022 Apr 21 The term "immuno-autonomics" has been coined to describe an emerging field evaluating the interaction between stress, autonomic nervous system (ANS), and inflammation. The field remains largely unknown among practicing rheumatologists. Our objective was to evaluate the perspectives of rheumatologists regarding the role of stress in the activity and management of rheumatoid arthritis (RA). A 31-item survey was conducted with 231 rheumatologists. Rheumatologists were asked to assess the role of stress in rheumatoid arthritis (RA) disease activity and were provided with information regarding immuno-autonomics. They were asked to consider how immuno-autonomics resonated with their patient management needs. The majority of rheumatologists are eager to better understand non-response, believe that stress biology and ANS dysfunction interfere with disease activity, and embrace the theory that measurement of ANS via next-generation HRV may be able to evaluate autonomic dysfunction and the biology of stress. Rheumatologists are open to the idea that quantitative measurement of ANS function using next-generation HRV can be a helpful tool to RA practice. The majority agree that ANS state influences RA disease control and that quantitative measures of ANS state are helpful to RA practice. Rheumatologists also agree that patients with poor ANS function may be at risk for not responding adequately to conventional, biologic, or targeted synthetic DMARDs. Almost all would use an in-office test to quantitatively measure ANS using next-generation HRV. This study shows that rheumatologists are open to embracing evaluation of ANS function as a possible tool in the management and treatment of RA.
34980014 Analysis of the first tear film break-up point in Sjögren's syndrome and non-Sjögren's s 2022 Jan 3 BACKGROUND: Tear film instability plays an important role in the course of Sjögren's Syndrome dry eye (SSDE) even though it is generally classified as aqueous-deficient dry eye. The measurement of the first tear film break-up point (FTBUP) helps to evaluate the most unstable position of the tear film on ocular surface. We aim to investigate FTBUP in Sjögren's Syndrome dry eye (SSDE) and non-Sjögren's Syndrome dry eye (NSSDE) patients, and explore its correlation with dry eye indices. METHODS: Twenty-two SSDE patients (44 eyes) and 22 NSSDE patients (44 eyes) were enrolled in the study. Oculus Keratograph K5M was used to measure FTBUP, the first and average non-invasive keratographic breakup time (f-NIKBUT and av-NIKBUT), the tear meniscus height, and meibomian gland dropout. Other tests of tear film were also performed including Ocular Surface Dryness Index (OSDI), Schirmer I test, fluorescein break-up time and corneal fluorescein staining. Dry eye indices and the locations of the FTBUP were compared between SSDE and NSSDE patients. Generalized estimating equation (GEE) was used to ajusted the correlations between right and left eyes. The correlations between the FTBUP and ocular symptoms and signs were investigated using Pearson's correlation coefficient test. RESULTS: The FTBUP occurred at the supranasal quadrant in 12/88 eyes, supratemporal quadrant in 8/88 eyes, inferonasal quadrant in 34/88 eyes, and inferotemporal quadrant in 34/88 eyes. The percentage eyes with inferior FTBUP was significantly higher in the SSDE than in the NSSDE subjects (86.3% vs 68.1%, P = .049). Moreover, in SSDE subjects, temporal breakup point was seen more often in those who presented corneal fluorescein staining in any location, while nasal breakup point was more frequent in those who did not present any corneal fluorescein staining (P = .045). CONCLUSION: The location of the FTBUP in SSDE patients had specific characteristics. However, the diagnostic potential of FTBUP in early recognition of SSDE needs further validation.
34387735 Cardiac involvement in primary SjÓ§gren's syndrome. 2022 Feb Primary SjÓ§gren's syndrome (pSS) is an autoimmune-mediated, inflammatory, and systemic connective tissue disease (CTD), especially in middle-aged women, which often involves multiple systems and organs of the body. In fact, the heart is an important target organ in patients with pSS. In recent years, it has been confirmed that the morbidity of cardiac involvement has increased in patients with pSS, and cardiovascular disease (CVD) is one of the main causes of death. The increased risk of CVD in pSS patients is associated with a great variety of risk factors, such as age, gender, hypertension, diabetes mellitus, dyslipidemia, disease duration, extra-glandular manifestations, therapeutic drugs of pSS, and so on. Early recognition and effective treatment of CVD may play a crucial role in improving adverse cardiovascular prognosis. Whereas cardiac involvement is closely related to patient prognosis and survival, the cardiac involvement of patients with pSS remains poorly studied. Therefore, this article reviews the cardiovascular risk factors, clinical manifestations of cardiac involvement, cardiovascular biomarkers, and therapeutic strategies of pSS patients.
35064306 CD30-targeted therapy induces apoptosis of inflammatory cytokine-stimulated synovial fibro 2022 Feb OBJECTIVE: It has been reported that levels of soluble CD30 in serum and joint fluid are significantly elevated in patients with rheumatoid arthritis (RA). This study aimed to investigate whether CD30 could be a therapeutic target for RA. METHODS: The expression and localization of CD30 were examined by immunohistochemical and double immunofluorescence staining on synovial tissue samples obtained from patients with RA or osteoarthritis (OA) during surgery. Changes in CD30 expression of fibroblast-like synoviocytes (FLS) from RA patients with or without TNFα and IL-1β stimulation were examined by the polymerase chain reaction (PCR) and flow cytometry. Collagen antibody-induced arthritis (CAIA) was created in DBA/1 mice, and the therapeutic effect of brentuximab vedotin (BV) was examined by clinical score, histological findings and measurement of serum levels of SAA, IL-6, and TNFα. RESULTS: CD30 expression was significantly higher in samples from patients with RA than from those with OA. Double immunofluorescence showed a low rate of co-localization of CD30 with CD20 or CD90, but a high rate of co-localization of CD30 and CD138. CD30 mRNA expression was upregulated 11.7-fold in FLS following stimulation by inflammatory cytokines. The clinical scores of CAIA mice were significantly lower following both BV treatments, however, the histological scores of CAIA mice were significantly lower only following treatment with high dose BV (70 mg/kg). CONCLUSIONS: CD30 was expressed on immunocompetent cells in synovial tissue from RA patients and in cytokine-stimulated FLS in vitro. High dose BV (70 mg/kg) showed significant therapeutic effects in ameliorating inflammation and joint destruction in CAIA mice, but low dose BV (30 mg/kg) was insufficient.
35075430 Bioinformatic Analysis Identifies Biomarkers and Treatment Targets in Primary Sjögren's S 2022 We aim to identify the common genes, biological pathways, and treatment targets for primary Sjögren's syndrome patients with varying degrees of fatigue features. We select datasets about transcriptomic analyses of primary Sjögren's syndrome (pSS) patients with different degrees of fatigue features and normal controls in peripheral blood. We identify common differentially expressed genes (DEGs) to find shared pathways and treatment targets for pSS patients with fatigue and design a protein-protein interaction (PPI) network by some practical bioinformatic tools. And hub genes are detected based on the PPI network. We perform biological pathway analysis of common genes by Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Lastly, potential treatment targets for pSS patients with fatigue are found by the Enrichr platform. We discovered that 27 DEGs are identified in pSS patients with fatigue features and the severe fatigued pSS-specific gene is RTP4. DEGs are mainly localized in the mitochondria, endosomes, endoplasmic reticulum, and cytoplasm and are involved in the biological process by which interferon acts on cells and cells defend themselves against viruses. Molecular functions mainly involve the process of RNA synthesis. The DEGs of pSS are involved in the signaling pathways of viruses such as hepatitis C, influenza A, measles, and EBV. Acetohexamide PC3 UP, suloctidil HL60 UP, prenylamine HL60 UP, and chlorophyllin CTD 00000324 are the four most polygenic drug molecules. PSS patients with fatigue features have specific gene regulation, and chlorophyllin may alleviate fatigue symptoms in pSS patients.
35006295 The relationship between the severity of oral dryness and the use of dry-mouth interventio 2022 Mar OBJECTIVE: Dry-mouth patients use different interventions to relieve their oral dryness. As recent studies showed that various subgroups of dry-mouth patients perceived different intra-oral regions as most dry, the present study investigated whether the use of dry-mouth interventions by various subgroups of dry-mouth patients was related to the perceived oral dryness as well as salivary flow rate. MATERIALS AND METHODS: Xerostomia Inventory (XI) scores, Regional Oral Dryness Score (RODI) scores and used dry-mouth interventions were extracted from the medical records of 528 patients visiting a saliva clinic. Based on their medical history, they were allocated into 6 subgroups. RESULTS: The subgroups of dry-mouth patients used a wide range of interventions to relieve their oral dryness. Sjögren's syndrome patients used most interventions more frequently than patients with oral dryness due to use of a limited number of medications and controls. Patients using medications showed associations between the total XI score and dry-mouth interventions aimed at the entire mouth. In medication using patients and controls, the locally applied intervention "using mouth gel" was associated with RODI scores of the anterior tongue. CONCLUSION: The use of dry-mouth interventions was associated with dry-mouth feelings. Use of interventions aimed to relieve dryness of the entire mouth was significantly associated with total XI score, while locally applied interventions were significantly associated with the severity of dryness at specific intra-oral regions, the anterior tongue in particular. CLINICAL RELEVANCE: The results will help clinicians to advise dry-mouth patients about the most suitable interventions for relief of oral dryness complaints.
35604471 Prevalence and characteristics of inflammatory rheumatic diseases in patients with thalass 2022 May 23 Reports of inflammatory rheumatic diseases (IRD) in thalassemia are limited. This study aimed to determine the prevalence and clinical characteristics of IRD in patients with thalassemia disease. Consecutive adult patients with thalassemia disease, confirmed by hemoglobin typing, attending the Hematology Clinic between June 2019 and May 2021 were invited to join this study. All of them had their history taken and a physical examination for IRD. Those with IRD had their medical records reviewed. Sixty-three patients (transfusion-dependent in 50) were included in this study. There was α-, β-, and co-inheritance of α- and β-thalassemia in 22.22%, 73.02%, and 4.76% of the patients, respectively, with β-thalassemia/Hb E disease in 53.97%. Twenty-three patients had IRD (rheumatoid arthritis in 9, gout in 6, systemic lupus erythematosus in 3, spondyloarthropathy in 2, and one patient each with dermatomyositis, overlap syndrome, and unclassified polyarthralgia). Clinical manifestations and laboratory findings were similar to IRD patients in general. In 40 patients without IRD, direct and indirect Coombs tests and antinuclear antibody (ANA) were positive in 51.72%, 27.59%, and 10.26%, respectively. When comparing among these 40 patients, between those with non-transfusion-dependent thalassemia (n = 10) and those with transfusion-dependent thalassemia (n = 30), the latter had non-significantly more positive direct Coombs (60.87% vs. 16.67%), indirect Coombs (30.43% vs. 16.67%), and ANA tests (13.33% vs. 0%). The prevalence of IRD in patients with thalassemia disease was rather high. Positive direct Coombs test and ANA were common in transfusion-dependent patients.
34953015 Gingival mesenchymal stem cell-derived exosomes are immunosuppressive in preventing collag 2022 Feb Due to the unsatisfied effects of clinical drugs used in rheumatoid arthritis (RA), investigators shifted their focus on the biotherapy. Although human gingival mesenchymal stem cells (GMSC) have the potential to be used in treating RA, GMSC-based therapy has some inevitable side effects such as immunogenicity and tumorigenicity. As one of the most important paracrine mediators, GMSC-derived exosomes (GMSC-Exo) exhibit therapeutic effects via immunomodulation in a variety of disease models, bypassing potential shortcomings of the direct use of MSCs. Furthermore, exosomes are not sensitive to freezing and thawing, and can be readily available for use. GMSC-Exo has been reported to promote tissue regeneration and wound healing, but have not been reported to be effective against autoimmune diseases. We herein compare the immunomodulatory functions of GMSC-Exo and GMSC in collagen-induced arthritis (CIA) model and in vitro CD4(+) T-cell co-culture model. The results show that GMSC-Exo has the same or stronger effects compared with GMSC in inhibiting IL-17A and promoting IL-10, reducing incidences and bone erosion of arthritis, via inhibiting IL-17RA-Act1-TRAF6-NF-κB signal pathway. Our results suggest that GMSC-Exo has many advantages in treating CIA, and may offer a promising new cell-free therapy strategy for RA and other autoimmune diseases.
35155468 Angiotensin Converting Enzyme Activity in Anti-TNF-Treated Rheumatoid Arthritis and Ankylo 2021 INTRODUCTION: Angiotensin-converting enzyme (ACE) and ACE2 have been implicated in the regulation of vascular physiology. Elevated synovial and decreased or normal ACE or ACE2 levels have been found in rheumatoid arthritis (RA). Very little is known about the effects of tumor necrosis factor α (TNF-α) inhibition on ACE or ACE2 homeostasis. In this study, we assessed the effects of one-year anti-TNF therapy on ACE and ACE2 production in RA and ankylosing spondylitis (AS) in association with other biomarkers. PATIENTS AND METHODS: Forty patients including 24 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 16 AS patients treated with ETN were included in a 12-month follow-up study. Serum ACE levels were determined by commercial ELISA, while serum ACE2 activity was assessed using a specific quenched fluorescent substrate. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. In addition, CRP, rheumatoid factor (RF) and ACPA were also measured. All assessments were performed at baseline and 6 and 12 months after treatment initiation. RESULTS: Anti-TNF therapy increased ACE levels in the full cohort, as well as in the RA and AS subsets. ACE2 activity increased in the full cohort, while the ACE/ACE2 ratio increased in the full cohort and in the RA subset (p < 0.05). Uni- and multivariable regression analyses determined associations between ACE or ACE/ACE2 ratios at different time points and disease duration, CRP, RF, FMD and IMT (p < 0.05). ACE2 activity correlated with CRP. The changes of ACE or ACE2 over 12 months were determined by treatment together with either RF or FMD (p < 0.05). CONCLUSIONS: Anti-TNF treatment may increase ACE and ACE2 in the sera of RA and AS patients. ACE and ACE2 may be associated with disease duration, markers of inflammation and vascular pathophysiology. The effects of TNF inhibition on ACE and ACE2 may reflect, in part, the effects of these biologics on the cardiovascular system.
35306615 Mechanistic and therapeutic links between rheumatoid arthritis and diabetes mellitus. 2022 Mar 20 Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible cartilage and bone damage. Despite its predominant osteoarticular and periarticular manifestations, RA is also a systematic disease associated with organ-specific extra-articular manifestation. Increasing evidence indicates that RA patients are susceptible to diabetes mellitus (DM), and RA aggravates metabolic disordered in DM, indicating the close association between RA and DM. Many factors involved in RA stimulate insulin resistance and DM development. These factors include proinflammatory cytokines (such as TNF-α, IL-6, IL-1β), RA autoantibodies (such as rheumatoid factor, cyclic citrullinated peptide antibodies), excess RA related adipokines (such as leptin, resistin, ANGPTL4), C-creative protein, and other protein (such as TXNDC5, NLRP3, RBP4). Furthermore, commonly used RA drugs, such as conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), and glucocorticoids, provide potential benefits in improving insulin resistance and inhibiting DM development. This review discusses the mechanistic and therapeutic links between RA and DM, aiming to provide valuable information for the prevention and treatment of DM in RA patients.
35046692 The Effects of Non-Surgical Periodontitis Therapy on the Clinical Features and Serological 2022 OBJECTIVE: The present study aims to evaluate the effects of basic periodontal disease therapy on the general condition and serum inflammatory indicators of patients with rheumatoid arthritis (RA) combined with chronic periodontitis (CP). METHODS: Forty patients with RA were enrolled in the study and, based on the results of an oral examination and in line with the 2018 periodontitis diagnostic criteria, they were divided into a group with CP (the RA + CP group) and a group without CP (the RA group). Twenty-nine patients with CP who attended the periodontal department of our hospital were recruited as a group with only CP (the CP group), and 20 volunteers without any systemic or periodontal disease were recruited as a healthy control group (the H group). The periodontal and joint conditions of the subjects in the four groups were recorded; anti-cyclic citrullinated protein antibodies, interleukin 6 (IL-6), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and rheumatoid factor levels, which reflect the severity of the RA, were detected, and the differences between the groups were analyzed. The probing depth (PD), clinical attachment loss, and sulcus bleeding index (SBI), which reflect the severity of the periodontitis, were correlated with the factor levels. The RA + CP and CP groups received therapeutic intervention, and the differences in each indicator before and six weeks after the treatment were compared, and their data were compared with those of patients in the RA group and H groups. RESULTS: Compared with the RA group, the serum expressions of ESR, CRP, and IL-6 were significantly higher in the RA + CP group. There were significant differences in the levels of PD, SBI, IL-6, and CRP in the patients receiving basic periodontal disease therapy before and after the treatment. CONCLUSION: A relatively large proportion of patients with RA have chronic periodontitis, and the local inflammatory state of CP might exacerbate the systemic inflammatory response in RA. Basic periodontal disease therapy may improve the oral condition of patients with RA and reduce the serum levels of the inflammatory factors.
35134994 Abatacept Ameliorates Both Glandular and Extraglandular Involvements in Patients With Sjö 2022 Feb 4 OBJECTIVE: To clarify the efficacy and safety of abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). PATIENTS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials) for SS with RA. The primary endpoint was the remission rate as measured by SDAI at 52 weeks after initiation of intravenous abatacept. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates during the study period were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled in this study. The mean SDAI decreased significantly from 23.6±13.2 (±SD) at baseline to 9.9±9.5 at 52 weeks (P<0.05). Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly from 2015.1±1695.4 (0 weeks) to 2311.3±1804.4 (24 weeks) mg/2 min (n=66, P<0.05). Tear volume increased significantly from 5.0±6.0 (0 weeks) to 5.6±6.3 (52 weeks) mm/5 min (n=52, P<0.05). Both ESSDAI and ESSPRI scores were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients, and 9 of these events were infections. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in patients with SS associated with RA.
35571141 Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF-1α and JAK3/STAT3 Sign 2022 Dihydroarteannuin (DHA), the primary element of artemisinin extracted from the traditional Chinese herb Artemisia annua L., has been used in malaria treatment for a long time. Recently, many studies have indicated that DHA also exhibits potent anti-rheumatoid arthritis (RA) activity. In this study, collagen-induced arthritis (CIA) in DBA/1J mice and inflammatory model in THP-1 cells were established to evaluate the modulatory effects of DHA on joint destruction and to explore the underlying mechanisms. Our results showed that DHA decreased the serum levels of IL-1β and IL-6, alleviated paw oedema, and reduced bone destruction in DBA/1J mice with CIA. Further exploration with the inflammatory model in THP-1 cells indicated that DHA reduced the protein expression of hypoxia-inducible factor (HIF)-1α and the phosphorylation in Janus kinase (JAK) 3 and signal transducer and activator of transcription (STAT) 3 protein, which resulted in a decrease in NOD-like receptor protein (NLRP) 3 expression and interleukin (IL)-1β release. Consequentially, the inflammatory activation in THP-1 cells was inhibited. Therefore, we concluded that DHA efficiently alleviated the inflammation and arthritic symptoms in CIA mice and downregulated inflammation in part by inhibiting NLRP3 expression via the HIF-1α and JAK3/STAT3 signaling pathway. Thus, DHA may be considered as a potential therapeutic agent in RA treatment.
33337813 The Risk of Presarcopenia Is Increased Among Female Patients With Primary Sjögren's Syndr 2022 Jan 1 OBJECTIVES: Sarcopenia is a progressive and generalized loss of muscle mass and function. The aim of this study was to evaluate the frequency of sarcopenia among patients with primary Sjögren's syndrome (SS) and the factors related with sarcopenia. METHODS: Forty-four female patients with primary SS and 44 female control subjects were included in this cross-sectional study between February and August 2019. Sarcopenia was evaluated by the handgrip test, Skeletal Muscle Mass Index, and gait speed test. RESULTS: Eleven patients (25.0%) had presarcopenia in the SS group and 2 (4.5%) in the control group (p = 0.007). Compared with control subjects, SS patients had lower results of hand grip and gait speed tests (p = 0.005 and p < 0.001, respectively). According to the Mini Nutritional Assessment Short Form, patients with presarcopenia had higher risk of malnutrition compared with patients without sarcopenia (p = 0.043). Patients with presarcopenia had higher scores in the European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index pain domain and patient visual analog scale for global disease activity compared with patients without sarcopenia (p = 0.044 and p = 0.036, respectively). In multivariate regression analysis, European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index pain was associated with hand grip strength (p = 0.016, R2 = 0.13) and Mini Nutritional Assessment Short Form was associated with Skeletal Muscle Mass Index (p = 0.005). CONCLUSIONS: Risk of sarcopenia is increased in patients with SS. Pain and malnutrition may contribute to presarcopenia. Evaluating pain and patient's global disease activity may help physicians to determine patients with increased risk of sarcopenia. Controlling disease activity and pain and preventing malnutrition may reduce the risk of development of sarcopenia.
35595956 MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-li 2022 May 20 Aberrant proliferation and migration of fibroblast-like synoviocytes (FLS) are major characteristics of rheumatoid arthritis (RA). MicroRNA-133 (miR-133) is a tumor-suppressive miRNA that targets various genes responsive for cell proliferation and migration. The aim of this study was to examine the effect of miR-133 on RA FLS. A high throughput miRNA microarray was performed in synovium from mice with collagen-induced arthritis (CIA). Expression levels of miR-133 and the putative targets were determined in synovium and FLS from patients with RA and mice with CIA. Overexpression of miR-133 in RA FLS was performed by lentiviral vector-mediated transfer of precursor miRNA (pre-miR). The expression of miR-133a/b was decreased in the joint tissue and FLS of CIA mice, as determined by miRNA array and qRT-PCR. Down-regulation of miR-133a/b expression could also be observed in synovium and FLS from patients with RA. Overexpression of miR-133 reduced cell viability and migration of RA FLS, with decreased levels of FSCN1, EGFR, and MET. Our findings demonstrated the inhibitory effects of miR-133 on FLS viability and migration, and might contribute to the pharmacologic development of miR-133 therapeutics in patients with RA.