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ID PMID Title PublicationDate abstract
34185454 Forkhead Box P3 (Foxp3) serum level and Foxp3 Gene-Promoter polymorphisms in Egyptian rheu 2021 Apr Regulatory T (Treg) cells are the chief player in induction of autotolerance and the transcription factor, Forkhead Box P3 (Foxp3), is the master regulator of their development and function. Polymorphisms in Foxp3 locus affect Foxp3 expression and can influence Treg cell function. This study aimed to determine the frequency of -3279C/A and -924A/G polymorphisms in the promoter region of the Foxp3 gene in Egyptian rheumatoid arthritis (RA) patients in comparison to apparently healthy controls, to test their association with Foxp3 serum levels as well as with patients' clinical and laboratory features. Also, to evaluate Foxp3 serum level as a putative measure of Foxp3+ Treg cells-mediated immune regulation and disease activity. A total of 136 subjects (68 RA patients and 68 controls) were studied for determining the frequency of both -3279 C/A and -924 A/G polymorphisms in the Foxp3 promoter region by PCR-RFLP and measuring their Foxp3 protein serum levels by ELISA. Our results indicated that; -3279 Foxp3 CA and AA genotypes were significantly higher in patients than controls (OR (95% CI) = 2.86 (1.31-6.26) and 2.79 (1.11-7.07), P= 0.008 and p = 0.03, respectively). Similarly, -924 AG genotype was significantly higher in patients than controls (OR (95% CI) = 2.92 (1.35-6.34); P=0.006). A significantly higher risk of RA was associated with the Foxp3 polymorphic variants -3279 A and -924 G. There was a statistically significant elevation in Foxp3 serum levels among patients, which was positively correlated to disease activity score and disease grade. In conclusion, Foxp3 polymorphisms influenced the risk of developing RA, but did not influence disease severity or activity. Serum level of Foxp3 is not a reliable indicator of Treg-mediated immune regulation in RA patients.
32979413 Sesquiterpene lactones; Damsin and neoambrosin suppress cytokine-mediated inflammation in 2021 Feb 10 ETHNOPHARMACOLOGIAL RELEVANCE: Although Damsissa (Ambrosia maritima) is traditionally used as anti-inflammatory and diuretic, the biological activity and mechanism of action of its major constituents are to be elucidated. AIM: to decipher the anti-arthritic potential of damsin (DMS) and neoambrosin (NMS) and to unfold their molecular signaling in complete Freund's adjuvant (CFA)-induced arthritis model. MATERIALS AND METHODS: the right hind paw was inoculated with CFA (0.1 ml) at day 0 and 7 while treatments were started from the 14(th) day and continued for 2 weeks. Rats were randomly assigned into 4 groups; normal group (NRML), CFA-induced arthritis group, CFA-induced arthritis treated with DMS and NMS (10 mg/kg/day) as 3(rd) and 4(th) group; respectively. RESULTS: Throughout experimental period, treatments ameliorated the increase of paw volume, knee joint diameter and nociception tests as reflected in open field arena. Also, DSM and NMS suppressed phosphorylation of Akt, STAT-3, ERK1/2 which was further mirrored by inactivation of GSK3β and downregulation of MCP-1 together with CCN1 and NF-kβ in hind paw tissue. Concomitantly, inflammation markers; TNF-α, IL-6, -12 were lowered as confirmed microscopically during examination of hind paw tissue. CONCLUSION: DSM and NMS-induced suppression of NF-kβ subdues clinical features of RA most probably through repression of Akt/ERK1/2/STAT3 pathway. Therefore, DMS and NMS can serve as safe and effective treatment for rheumatoid arthritis, one of the most disabling chronic, inflammatory and painful autoimmune disease.
33060309 Benefits of Methotrexate Use on Cardiovascular Disease Risk Among Rheumatoid Arthritis Pat 2021 Jun OBJECTIVE: Methotrexate (MTX) has been associated with reduced risk for cardiovascular disease (CVD) events among patients with rheumatoid arthritis (RA) not exposed to biologic disease-modifying antirheumatic drugs (bDMARDs). The effect of concomitant MTX on CVD risk among RA patients initiating bDMARDs remains unknown. METHODS: A retrospective cohort study was conducted to assess the effect of MTX on CVD risk using 2006-2015 Medicare claims data for patients with RA initiating bDMARD. The main exposure was current use of MTX, updated in a time-varying fashion. The primary outcome was a composite of incident myocardial infarction (MI), stroke, and fatal CVD. Secondary outcomes were each event that comprised the primary outcome. Incidence rates (IR) and 95% CI were calculated using Poisson regression. Associations between MTX and risk of CVD were assessed using Cox regression. RESULTS: A total of 88,255 bDMARD initiations and 1861 CVD events were included in this study. Mean age was 64.6 (12.3) years, 84.0% were female, and 68.2% were non-Hispanic White. The crude IRs (95% CI) for CVD were 17.9 (16.9-18.8) and 12.1 (11.1-13.2) per 1000 patient-years among MTX unexposed and exposed, respectively. The multivariable adjusted HR (95% CI) for CVD events associated with MTX was 0.76 (0.68-0.85). Multivariable adjusted HRs were 0.78 (0.66-0.91), 0.74 (0.62-0.88), 0.77 (0.68-0.86), and 0.82 (0.73-0.93) for MI, stroke, MI or stroke, and a composite CVD outcome, respectively. Results were robust in sensitivity and subgroup analyses. CONCLUSION: Among patients with RA receiving biologics, concomitant MTX use was associated with a 24% lower risk for CVD events.
33452171 Use of Hydroxychloroquine and Risk of Heart Failure in Patients With Rheumatoid Arthritis. 2021 Oct OBJECTIVE: To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA). METHODS: In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. RESULTS: The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). CONCLUSION: Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA.
35046954 Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatmen 2021 BACKGROUND: The goal of this study was to identify potential predictive biomarkers for the therapeutic effect of infliximab (IFX) in Rheumatoid arthritis (RA) and explore the potential molecular mechanism of nonresponse to IFX treatment to achieve individualized treatment of RA. METHODS: Differential gene expression between IFX responders and nonresponders in the GSE58795 and GSE78068 datasets was identified. Coexpression analysis was used to identify the modules associated with nonresponse to IFX therapy for RA, and enrichment analysis was conducted on module genes. Least absolute shrink and selection operator (LASSO) regression was used to develop a gene signature for predicting the therapeutic effect of IFX in RA, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the signature. Correlation analysis and single-sample gene set enrichment analysis (ssGSEA) were used to explore the potential role of the hub genes. Experimental validation was conducted in synovial tissue and RA fibroblast-like synoviocytes (RA-FLSs). RESULTS: A total of 46 common genes were obtained among the two datasets. The yellow-green module was identified as the key module associated with nonresponse to IFX therapy for RA. We identified a 25-gene signature in GSE78068, and the AUC for the signature was 0.831 in the internal validation set and 0.924 in the GSE58795 dataset(external validation set). Derlin-1 (DERL1) was identified as the hub gene and demonstrated to be involved in the immune response and autophagy regulation. DERL1 expression was increased in RA synovial tissue compared with OA synovial tissue, and DERL1-siRNA partially inhibited autophagosome formation in RA-FLSs. CONCLUSION: The 25-gene signature may have potential predictive value for the therapeutic effect of IFX in RA at the beginning of IFX treatment, and autophagy may be involved in nonresponse to IFX treatment. In particular, DERL1 may be associated with the regulation of autophagy.
32588130 [Association of physical activity with fatigue and functional capacity in patients with rh 2021 Mar BACKGROUND: Patients with rheumatoid arthritis (RA) tend to be less physically active. Physical activity has been shown to have a positive impact on disease activity and quality of life and is recommended by the European League Against Rheumatism (EULAR) as an integral component of standard treatment. OBJECTIVE: A cross-sectional analysis of RA patients was carried out assessing disease activity, functional capacity and fatigue associated with physical activity. MATERIAL AND METHODS: Physical activity, functional capacity and the global fatigue index (GFI) were examined using standardized questionnaires: the international physical activity questionnaire short form (IPAQ-SF), the functional questionnaire Hannover (FFbH) and the multidimensional assessment of fatigue (MAF). The data were evaluated using SPSS 26 (IBM, Armonk, NY, USA). The level of significance was tested with bivariate and partial correlations and nonparametric tests. RESULTS: In total 164 patients were included in the study. The majority of the patients were female (127/164; 77%) and the median age of the cohort was 58.3 years (range 21-86 years). The median duration of disease-related symptoms at inclusion was 169 months (range 0-713 months). Physical activity was low in 39%, moderate in 37% and high in 24%. Patients reporting higher levels of physical activity reported significantly lower GFI (p < 0.001), functional limitations (p < 0.001) and disease activity (p = 0.045) scores than those with less physical activity. CONCLUSION: Physical activity in RA patients was significantly correlated with functional capacity and levels of fatigue. In order to reduce the proportion of patients with low physical activity, the possibilities for functional training should be expanded and the patients should be encouraged to undertake sporting activities.
34779007 Metabolic reprogramming of macrophages instigates CCL21-induced arthritis. 2022 Feb This study was designed to delineate the functional significance of CCL21 in metabolic reprogramming in experimental arthritis and differentiated rheumatoid arthritis (RA) macrophages (MΦs). To characterize the influence of CCL21 on immunometabolism, its mechanism of action was elucidated by dysregulating glucose uptake in preclinical arthritis and RA MΦs. In CCL21 arthritic joints, the glycolytic intermediates hypoxia-inducible factor 1α (HIF1α), cMYC and GLUT1 were overexpressed compared with oxidative regulators estrogen-related receptor γ and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1)-α. Interestingly, 2-deoxy-D-glucose (2-DG) therapy mitigated CCL21-induced arthritis by restraining the number of joint F4/80(+) iNOS(+) MΦs without impacting F4/80(+) Arginase(+) MΦs. Similar to the preclinical findings, blockade of glycolysis negated CCL21-polarized CD14(+) CD86(+) GLUT(+) MΦ frequency; however, CD14(+) CD206(+) GLUT(+) MΦs were not implicated in this process. In CCL21-induced arthritis and differentiated RA MΦs, the inflammatory imprint was uniquely intercepted by 2-DG via interleukin-6 (IL-6) downregulation. Despite the more expansive inflammatory response of CCL21 in the arthritic joints relative to the differentiated RA MΦs, 2-DG was ineffective in joint tumor necrosis factor-α, IL-1β, CCL2 and CCL5 enrichment. By contrast, disruption of glycolysis markedly impaired CCL21-induced HIF1α and cMYC signaling in arthritic mice. Notably, in RA MΦs, glycolysis interception was directed toward dysregulating CCL21-enhanced HIF1α transcription. Nonetheless, in concurrence with the diminished IL-6 levels, CCL21 differentiation of CD14(+) CD86(+) GLUT1(+) MΦs was reversed by glycolysis and HIIF1α inhibition. Moreover, in the CCL21 experimental arthritis or differentiated RA MΦs, the malfunctioning metabolic machinery was accompanied by impaired oxidative phosphorylation because of reduced PGC1α or peroxisome proliferator-activated receptor-γ expression. CCL21 reconfigures naïve myeloid cells into glycolytic RA CD14(+) CD86(+) GLUT(+) IL-6(high) HIF1α(high) MΦs. Therefore, inhibiting the CCL21/CCR7 pathway may provide a promising therapeutic strategy.
33258021 [Calcium, phosphate and the calcium-sensing receptor : A proinflammatory combination in r 2021 Feb Calcium and phosphate are necessary for the functionality of the organism and the cellular metabolism. In the form of hydroxyapatite, calcium and phosphate stabilize bone and teeth, but deposition of calcium phosphate in soft tissue or the vasculature can have devastating consequences. To prevent ectopic calcification, calcium and phosphate are stabilized by fetuin-A/alpha-2-HS-glycoprotein as non-crystalline, 60-100 nm-sized calciprotein particles (CPP) in extracellular fluids. An increase of the CPP concentration in the extracellular fluid beyond a certain threshold results in pro-inflammatory responses in monocytes and macrophages, which includes the activation of the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome resulting in the release of interleukin-1β and interleukin-18. The release of pro-inflammatory cytokines as a result of increased CPPs is enhanced in rheumatoid arthritis (RA). The calcium-sensing receptor plays a major role in this mechanism by modulating the uptake (macropinocytosis) of CPPs and thereby increasing the pro-inflammatory potential. Bone erosion and subsequent release of calcium and phosphate during the etiopathology of RA can therefore aggravate the joint inflammation in this disease.
33243069 Detection of human cytomegalovirus in synovial neutrophils obtained from patients with rhe 2021 May Objectives: To examine whether signs of an active human cytomegalovirus (HCMV) infection are present in affected joints of patients with rheumatoid arthritis (RA).Method: Polymorphonuclear leucocytes (PMNLs) were obtained from synovial fluid (SF) of 17 RA patients and were analysed for HCMV-pp65 and HCMV-immediate early (IE) proteins using the antigenemia assay. Peripheral blood (PB) and SF obtained from these 17 patients and from 17 additional RA patients (n = 34) were tested for HCMV-IE and pp150 DNA with Taqman polymerase chain reaction. Plasma samples from the patients were analysed for HCMV-immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay and compared to 71 healthy gender-matched blood donors.Results: HCMV-pp65 protein was detected in 65% of synovial PMNL samples, but in only 18% of PMNLs from PB. In contrast, HCMV IE protein was not found in any of the analysed PMNL samples. On the DNA level, HCMV-IE and pp150 DNA was detected in SF of 13/32 (41%) and 14/23 (61%) of RA patients, respectively. HCMV-IE and pp150 DNA was also found in 24/33 (73%) and in 16/24 (67%) of PB samples obtained from RA patients, respectively. HCMV IgG seroprevalence was 76% in RA patients as well as in healthy controls, while only one RA patient was positive for specific IgM.Conclusions: HCMV pp65 antigen was found in PMNLs from SF of RA patients, indicating an active infection in the affected joint. Future studies are needed to determine whether HCMV infection can aggravate the inflammatory process in these patients.
34664264 Azithromycin alleviates the severity of rheumatoid arthritis by targeting the unfolded pro 2022 Mar BACKGROUND AND PURPOSE: Azithromycin is a macrolide antibiotic with anti-inflammatory properties. We aim to substantiate the treatment potential of azithromycin in rheumatoid arthritis. EXPERIMENTAL APPROACH: Gene expression profiles were collected by RNA sequencing and the effects of azithromycin were assessed by in vitro and in vivo assays on the effects of azithromycin-mediated blockade of glucose-regulated protein 78 (GRP78). Anti-inflammatory activity of azithromycin was measured in fibroblast-like synoviocytes from rheumatoid arthritis patients and in collagen-induced arthritis in DBA/1 mice. Characterization of the binding of azithromycin to GRP78 was performed using drug affinity responsive target stability, proteomics and cellular thermal shift assays. Azithromycin-mediated inhibition of GRP78 and its relationship to its anti-arthritic activity was assessed. KEY RESULTS: Azithromycin reduced proinflammatory factor production, cell migration, invasion and chemoattraction and enhanced apoptosis, reducing the deleterious inflammatory response of rheumatoid arthritis fibroblast-like synoviocytes in vitro. Azithromycin ameliorated the severity of collagen-induced arthritis lesions as efficiently as the TNFα inhibitor etanercept. Transcriptional analyses suggested that azithromycin treatment impairs signalling cascades associated with cholesterol and lipid biosynthesis. GRP78 was identified as a novel target of azithromycin. Azithromycin-mediated activation of the unfolded protein response via the inhibition of GRP78 activity is required not only for inducing the expression of C/EBP-homologous protein (ChOP) but also for the activating sterol-regulatory element binding protein (SREBP) and its targeted genes involved in cholesterol and lipid biosynthetic processes. Furthermore, deletion of GRP78 abolished the anti-arthritic activity of azithromycin. CONCLUSION AND IMPLICATIONS: These findings indicate that azithromycin can used to treat rheumatoid arthritis.
33169172 Expression profile and diagnostic value of circRNAs in peripheral blood from patients with 2021 Jan Circular RNAs (circRNAs) have gained attention due to their performance in disease diagnosis. However, the characteristics of circRNAs in peripheral blood from patients with systemic lupus erythematosus (SLE) remain unknown. Therefore, the aim of the present study was to determine the expression profile and diagnostic potential of circRNAs in peripheral blood from patients with SLE. The global circRNA expression in the peripheral blood of patients with SLE and healthy controls (HCs) was detected using a circRNA microarray. Then, the expression levels of three upregulated circRNAs were selected for further validation by reverse transcription‑quantitative PCR (RT‑qPCR) in a training set. Moreover, the diagnostic value of these circRNAs was assessed by constructing a receiver operating characteristic curve, and then verified in a blind testing set. In total, 1,566 circRNAs were identified to be dysregulated between patients with SLE and HCs (≥2 fold change, P<0.05). Furthermore, the RT‑qPCR results were consistent with the microarray data, in that all three selected circRNAs, hsa_circ_0082688, hsa_circ_0082689 and hsa_circ_0008675, were significantly upregulated in patients with SLE (P<0.05). Results from the training set demonstrated that the combination of hsa_circ_0082688‑hsa_circ_0082689 may provide the most beneficial diagnostic potential. Moreover, the blind test results indicated that the combination model of hsa_circ_0082688‑hsa_circ_0082689 could effectively discriminate between patients with SLE from patients with rheumatoid arthritis and HCs, with a sensitivity of 91.30%, a specificity of 78.57% and an accuracy of 82.28%. Moreover, the combination model of hsa_circ_0082688‑hsa_circ_0082689 + anti‑dsDNA could more effectively discriminated the SLE group from the control groups, with a sensitivity of 95.65%, a specificity of 100.00% and an accuracy of 98.73%. In addition, correlation analysis results suggested that all three circRNAs in patients with SLE did not correlate with the SLE disease activity index. In conclusion, the expression levels of hsa_circ_0082688‑hsa_circ_0082689 may serve as potential biomarkers for SLE diagnosis.
34333352 Imaging of facet joint diseases. 2021 Dec Facet joints are the important articular pillars of the spine. Several pathologies can occur in and around the facet joint, including extra ossicles, traumatic dislocation, osteoarthritis, synovial cyst, axial spondyloarthritis, rheumatoid arthritis, calcium pyrophosphate deposition disease, septic arthritis, and malignant and benign neoplasms. Imaging is the mainstay to detect and characterize these diseases. In this review, we discuss the anatomy and function of facet joints, imaging techniques, and the imaging findings of several facet joint diseases. This information may be helpful to radiologists to make the correct diagnosis and optimize the management of patients with facet joint diseases.
34351967 Influence of dietary habits on depression among patients with rheumatoid arthritis: A cros 2021 OBJECTIVE: Although mental disorder is one of the most common comorbidities of rheumatoid arthritis (RA) and is known as a critical influence on RA remission rates, there is little knowledge regarding a possible therapeutic strategy for depression or anxiety in a RA population. Most recently, clinical evidence of dietary improvement for depression has emerged in a general population, but the relationship between dietary habits and mental disorder has not been investigated in RA. The purpose of this study is to elucidate clinical associations between mental disorder (depression/anxiety), dietary habits and disease activity/physical function in patients with RA. METHODS: A cross-sectional study was performed with 267 female outpatients from the KURAMA database. Using the Hospital Anxiety and Depression Scale (HADS), we classified the participants into three groups by depression state, and their characteristics were compared. Using the 20-items on the self-reported food frequency questionnaire, we investigated the relationship between dietary habits and depression or anxiety, adopting a trend test and a multivariate standardized linear regression analysis for the HADS score of depression or that of anxiety as a dependent variable. RESULTS: According to the classified stage of depression, current disease activity (DAS28-CRP: 28-Joint RA Disease Activity Score-C-reactive protein) and the health assessment questionnaire disability Index (HAQ-DI) were significantly increased. Trend analyses revealed that the depression score was inversely associated with the consumption of three food (fish, vegetables and fruit) out of twenty as was the anxiety score with only fish intake. Furthermore, multiple linear regression analysis revealed that the depression score was negatively associated with frequent fish intake (≥ 3 times per week) (Estimate -0.53, p = 0.033), HAQ-DI score within normal range (Estimate -0.88, p ≤ 0.001) and MTX use (Estimate -0.60, p ≤ 0.023). For the anxiety score, multivariate analysis showed similar but not significant associations with variables except for HAQ-DI score. CONCLUSIONS: In a RA population, both depression and anxiety had a significant and negative association with HAQ-DI score, and depression rather than anxiety had negative association with frequent fish intake. Modification of dietary habits such as increased fish consumption may have a beneficial effect on the depression state in RA patients.
33583939 Polymorphisms in IRF5 and TYK2 Genes Are Associated with Rheumatoid Arthritis in a Chinese 2021 Feb 15 BACKGROUND The IRF5 and TYK2 gene polymorphisms are associated with autoimmune diseases. However, the relationship between the IRF5 and TYK2 gene polymorphisms and RA risk in the Chinese Han population was inconsistent. MATERIAL AND METHODS A total of 578 RA patients (case group) and 578 healthy controls (control group) were assessed in a case-control study. Genotyping of IRF5 (Exon 6 insertion/deletion (in/de), rs2004640, rs2070197, rs10954213) and TYK2 (rs280500, rs280519, rs280521, rs8108236, rs12720253) was performed by direct sequencing method. Data analysis was performed by SHEsis. RESULTS The rs2004640T allele (P=0.0003) and the dominant (P=0.001) and recessive (P=0.01) models of rs2004640 were associated with RA risk after stringent Bonferroni correction (0.05/4). The IRF5 exon 6 (in), rs2070197 and rs10954213 were not associated with RA (P>0.05). Two haplotypes of IRF5 (DTAT and DTGG) were associated with RA susceptibility (P<0.05). In addition, the frequencies of TYK2 rs280500A, rs280521A, and rs8108236A were significantly higher in the RA group compared with the control group (P<0.05). TYK2 rs280500, rs280521, and rs8108236 were associated with RA susceptibility in the dominant model, but the same was not observed for rs280519 and rs12720253 (P<0.05). Furthermore, 3 risk haplotypes (AAAGT, AGGAT, and GAAAT) and a protective haplotype (GAGGT) of TYK2 gene were associated with RA susceptibility (P<0.05). CONCLUSIONS Our results suggest that IRF5 rs2004640, TYK2 rs280500, rs280521, rs8108236, and haplotypes IRF5 (DTAT and DTGG) and TYK2 (AAAGT, AGGAT, GAAAT, and GAGGT) are susceptible factors for RA in a Chinese Han population.
34128788 Catastrophisation, chronic pain and sexuality: a cross-sectional investigation in fibromya 2021 May OBJECTIVES: In the present study we investigate the putative differences in pain catastrophising (PC), pain perception (PP), sexual functioning (SF), satisfaction (SS), and overall quality of life between fibromyalgia (FM) and rheumatoid arthritis (RA) patients as compared to healthy controls (HC). METHODS: Fifty-seven native Italian-speaking female individuals suffering either from FM or RA and thirty-eight healthy female controls (FM = 40; RA = 17; HC = 38) were submitted to a semi-structured interview aimed at assessing PP intensity (Visual Analog Scale; VAS), general health conditions (36-items Short-Form Health Survey; SF-36), PC (Pain Catastrophising Scale; PCS), SF and SS (Index of Sexual Satisfaction; ISS/ Female Sexual Function Index; FSFI). RESULTS: FM patients had a significantly higher PP both as compared to RA and HC (p<0.002 for both), and higher PC as compared to HC but not as compared to RA patients (p<0.03 and p<0.64). When compared to RA patients and HC, they showed a lower quality of life (p<0.002 for both comparisons), a compromised SF (p<0.003 and p<0.002, respectively) and a lower index of SS with respect to HC (p<0.002). RA patients had higher PP (VAS; p<0.002), lower quality of life and SF as compared to HC (p<0.002 and p<0.003, respectively). CONCLUSIONS: FM and RA patients showed a significantly lower quality of life, SF and SS as compared to HC. PC was significantly related to PP and low quality of life in FM patients while in RA patients it negatively affected quality of life and especially the sexual sphere both when considering SF and SS.
33316402 Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic diseas 2021 Apr OBJECTIVES: Early in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ. METHODS: We conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, χ(2), and Student's t-tests. RESULTS: As of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200-400 mg/day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86). CONCLUSIONS: HCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.
33976334 Increased disease activity in early arthritis patients with anti-carbamylated protein anti 2021 May 11 The initial management of rheumatoid arthritis (RA) has a high impact on disease prognosis. Therefore, we need to select the most appropriate treatment as soon as possible. This goal requires biomarkers of disease severity and prognosis. One such biomarker may be the presence of anti-carbamylated protein antibodies (ACarPA) because it is associated with adverse long term outcomes as radiographic damage and mortality. Here, we have assessed the ACarPA as short-term prognostic biomarkers. The study was conducted in 978 prospective early arthritis (EA) patients that were followed for two years. Our results show the association of ACarPA with increased levels of all the disease activity measures in the first visit after arthritis onset. However, the associations were more significant with the high levels in local measures of inflammation and physician assessment than with the increases in systemic inflammation and patient-reported outcomes. More notably, disease activity was persistently increased in the ACarPA positive patients during the two years of follow-up. These differences were significant even after accounting for the presence of other RA autoantibodies. Therefore, the ACarPA could be considered short-term prognostic biomarkers of increased disease activity in the EA patients.
33408335 Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibr 2021 Jan Histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses, but the role of HRF/TCTP in rheumatoid arthritis (RA) remains undefined. In this study, we explored the pathogenic significance of HRF/TCTP and evaluated the therapeutic effects of HRF/TCTP blockade in RA. HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine the experimental phenotypes of RA. HRF/TCTP levels in the sera of RA patients were measured and compared to those from patients with osteoarthritis (OA), ankylosing spondylitis, Behçet's disease, and healthy controls. HRF/TCTP expression was also assessed in the synovium and fibroblast-like synoviocytes (FLSs) obtained from RA or OA patients. Finally, we assessed the effects of HRF/TCTP and dimerized HRF/TCTP-binding peptide-2 (dTBP2), an HRF/TCTP inhibitor, in RA-FLSs and CIA mice. Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels in the sera, synovial fluid, synovium, and FLSs were higher in patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with RA disease activity. The tumor-like aggressiveness of RA-FLSs was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice and had no detrimental effects in a murine tuberculosis model. Our results indicate that HRF/TCTP is a novel biomarker and therapeutic target for the diagnosis and treatment of RA.
34238376 Pathogenic implications, incidence, and outcomes of COVID-19 in autoimmune inflammatory jo 2021 Jul 8 As the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly, there are still many unresolved questions of how this virus would impact on autoimmune inflammatory joint diseases and autoinflammatory disorders. The main aim of this paper is to describe the main studies focusing their attention on COVID-19 incidence and outcomes of rheumatoid arthritis (RA), spondylarthritis (SpA), and autoinflammatory disease cohorts. We also revised possible pathogenic mechanisms associated with. Available data suggest that, in patients with RA and SpA, the immunosuppressive therapy, older age, male sex, and the presence of comorbidities (hypertension, lung disease, diabetes, CVD, and chronic renal insufficiency/end-stage renal disease) could be associated with an increased risk of infections and high rate of hospitalization. Other studies have shown that lower odds of hospitalization were associated with bDMARD or tsDMARDs monotherapy, driven largely by anti-TNF therapies. For autoinflammatory diseases, considering the possibility that COVID-19 could be associated with a cytokine storm syndrome, the question of the susceptibility and severity of SARS-CoV-2 infection in patients displaying innate immunity disorders has been raised. In this context, data are very scarce and studies available did not clarify if having an autoinflammatory disorder could be or not a risk factor to develop a more severe COVID-19. Taking together these observations, further studies are likely to be needed to fully characterize these specific patient groups and associated SARS-CoV-2 infection.
34624807 Anti-inflammatory natural products as potential therapeutic agents of rheumatoid arthritis 2021 Dec BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing severe locomotor disability and deterioration in the quality of life. Existing treatments for RA mainly focus on the use of immunomodulators and the suppression of synovial inflammation, and many have significant side effects. Medicinal plants are regarded as important alternative sources for treating RA. PURPOSE: This review summarizes the bioactive compounds of medicinal plants, which have been shown to modulate the immune response by regulating interleukins in vitro and in vivo experimental models, and that may be promising substances for use in the treatment of RA. METHODS: Articles on natural products used for the management of arthritis were retrieved from PubMed, Embase, Scopus, and Web of Science through electronic and manual search in English. In total, 576 publications were identified, and 34 were included in this systematic review. RESULTS: Two articles presented findings on the role of natural components in the treatment of arthritis in both in vitro and in vivo studies. Nine reports defined the role of plant-derived natural molecules in the treatment of arthritis using cell lines, and 27 in vivo studies assessed the anti-arthritic efficacy and immunomodulation effects of phytoconstituents on interleukin production and inflammatory responses. CONCLUSION: This systematic review broadly reports that, in contrast to other classes of phytochemicals, flavonoids have the greatest therapeutic potential against arthritis by modulating the expression of pro-inflammatory TNF-α, IL-1β, IL-6, IL-8, and IL-17, as well as anti-inflammatory IL-2 and IL-10 cytokines, through the suppression of dynamic inflammatory biomarkers.