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ID PMID Title PublicationDate abstract
32740860 A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeu 2021 Oct Activated neutrophils release neutrophil extracellular traps (NETs) in response to a variety of stimuli. NETosis is driven by protein-arginine deiminase type 4, with the release of intracellular granule components that function by capturing and destroying microbes, including viral, fungal, bacterial, and protozoal pathogens. The positive effects of pathogen control are countered by pro-inflammatory effects as demonstrated in a variety of diseases. Components of NETS are non-specific, and other than controlling microbes, they cause injury to surrounding tissue by themselves or by increasing the pro-inflammatory response. NETs can play a role in enhancement of the inflammation seen in autoimmune diseases including psoriasis, rheumatoid arthritis, and systemic lupus erythematosis. In addition, autoinflammatory diseases such as gout have been associated with NETosis. Inhibition of NETs may decrease the severity of many diseases improving survival. Herein, we describe NETosis in different diseases focusing on the detrimental effect of NETs and outline possible therapeutics that can be used to mitigate netosis. There is a need for more studies and clinical trials on these and other compounds that could prevent or destroy NETs, thereby decreasing damage to patients.
34239010 A myostatin-CCL20-CCR6 axis regulates Th17 cell recruitment to inflamed joints in experime 2021 Jul 8 The interactions of fibroblast-like synoviocyte (FLS)-derived pro-inflammatory cytokines/chemokines and immune cells support the recruitment and activation of inflammatory cells in RA. Here, we show for the first time that the classical myokine myostatin (GDF-8) is involved in the recruitment of Th17 cells to inflammatory sites thereby regulating joint inflammation in a mouse model of TNFalpha-mediated chronic arthritis. Mechanistically, myostatin-deficiency leads to decreased levels of the chemokine CCL20 which is associated with less infiltration of Th17 cells into the inflamed joints. In vitro, myostatin alone or in combination with IL-17A enhances the secretion of CCL20 by FLS whereas myostatin-deficiency reduces CCL20 secretion, associated with an altered transmigration of Th17 cells. Thus, the communication between activated FLS and Th17 cells through myostatin and IL-17A may likely contribute to a vicious cycle of inflammation, accounting for the persistence of joint inflammation in chronic arthritis. Blockade of the CCL20-CCR6 axis by inhibition of myostatin may, therefore, be a promising treatment option for chronic inflammatory diseases such as arthritis.
33103383 Biofunctionalized Liposomes to Monitor Rheumatoid Arthritis Regression Stimulated by Inter 2021 Jan Even after the revolution of rheumatoid arthritis (RA) treatment with biologic agents, this debilitating disease remains a major clinical problem. The outstanding outcomes of the systemic administration of antibodies (Abs) are narrowed by the risk of serious side effects and limited efficacy due to their short half-life. Interleukin-23 (IL-23) is a crucial pro-inflammatory cytokine involved in inflammation that potently enhances the generation of T-helper type-17 (Th17) cells. Hence, in this work, anti-IL-23 Abs are immobilized at the surface of liposomes to increase their therapeutic efficacy, being gold nanoparticles (AuNPs) incorporated to allow monitoring the biodistribution of the liposomes after systemic administration as well as due to their anti-inflammatory and antioxidant effects. A stable monodispersed liposomes' suspension with around 130 nm is produced and efficiently biofunctionalized with anti-IL-23 Abs. IL-23 capture and neutralization capacity are confirmed using activated macrophages. Biological assays demonstrate their hemocompatibility and cytocompatibility with human articular chondrocytes, macrophages, and endothelial cells. Moreover, the neutralization of IL-23 by the biofunctionalized liposomes efficiently decreases the production of IL-17A by peripheral blood mononuclear cells of healthy donors and RA patients who are activated to Th17 differentiation. Therefore, the developed formulation may be a promising strategy to treat RA.
32403900 Association of body composition with disease activity and disability in rheumatoid arthrit 2021 Jan BACKGROUND/AIMS: To explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA). METHODS: The study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined as BMI ≥ 25 kg/m2. RESULTS: The median (interquartile range) disease duration was 6 years (3.5 to 9) and the mean DAS28 score was 3.6 ± 1.1. The mean BMI was 23.6 ± 3.6 kg/m2 and 109 patients (32.5%) were obese. Compared with non-obese patients, obese patients had a higher C-reactive protein (1.68 mg/dL vs. < 0.1 mg/dL, p = 0.013), higher pain VAS score (40 vs. 35, p = 0.031), and higher DAS28-erythrocyte sedimentation rate score (3.75 ± 1.18 vs. 3.46 ± 1.11, p = 0.031). In multivariate regression analysis, the DAS28 score in females was positively associated with the current steroid dose, body fat mass, and HAQ score, while the HAQ score in females was associated with older age, DAS28, lower skeletal muscle mass, and higher body fat/skeletal muscle ratio. In the multivariate regression analysis, the DAS28-P score in females was positively associated with body fat/skeletal muscle ratio and HAQ. CONCLUSION: Body composition, such as the body fat mass and body fat/skeletal muscle ratio, is significantly associated with disease activity and disability in female RA patients.
34263635 A systematic review and meta-analysis: effects of glucocorticoids on rheumatoid arthritis 2021 Jul BACKGROUND: Meta-analysis was performed to explore the efficacy of glucocorticoids in the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to provide a theoretical basis for the clinical treatment of patients. METHODS: Relevant literatures from the establishment of the database to December 31, 2020, were searched from databases such as PubMed. The literatures with randomized controlled trial of the clinical efficacy of glucocorticoids in the treatment of RA and SLE were screened for meta-analysis. RESULTS: Eleven documents were included, including 1,298 participants. It was found that the cardiovascular system [mean difference (MD) =1.23; 95% confidence interval (CI): 0.64 to 2.34; Z=0.62; P=0.53], respiratory system (MD =1.87; 95% CI: -0.66 to 5.29; Z=1.18; P=0.24), nervous system (MD =1.22; 95% CI: 0.25-5.84; Z=0.25; P=0.8), visual impairment (MD =1.41; 95% CI: 0.79-2.52; Z=1.15; P=0.25), endocrine system (MD =8.53; 95% CI: 2.71-26.88; Z=3.66; P=0.0003), digestive system (MD =1.41; 95% CI: 0.76-2.63; Z=1.09; P=0.28), genitourinary system (MD =1.06; 95% CI: 0.35-3.17; Z=0.1; P=0.92), blood system (MD =2.96; 95% CI: 0.62-14.26; Z=1.35; P=0.18), Z=0.48; P=0.63), infection status (MD =1.36; 95% CI: 0.98-1.87; Z=1.86; P=0.06), clinical efficacy (MD =1.79; 95% CI: 1.27-2.52; Z=3.32; P=0.0009), pain (MD =1.16; 95% CI: 0.76-1.78; Z=0.68; P=0.5), and joint swelling score (MD =0.03; 95% CI: -0.38 to 0.45; Z=0.15; P=0.88) of experimental group after treatment were all superior versus controls. However, the skin and mucous membranes (MD =0.87; 95% CI: 0.55-1.37; Z=0.61; P=0.54), musculoskeletal (MD =0.85; 95% CI: 0.43-1.66; Z=0.48; P=0.63), radiation injury (MD =-1.93; 95% CI: -3.68 to -0.18; Z=2.17; P=0.03), and C-reactive protein (CRP) level (MD =-8.66; 95% CI: -10.16 to -7.16; Z=11.34; P<0.00001) of experimental group were inferior to those of control group. DISCUSSION: Glucocorticoids in the treatment of RA and SLE can improve the clinical efficacy, but it was easy to cause multiple system adverse reactions. Therefore, the clinical treatment should follow the doctor's advice.
34462262 Joint inflammation tends to recur in the same joints during the rheumatoid arthritis disea 2022 Feb OBJECTIVES: We investigated whether local joint swelling recurs in the same joints over time in patients with rheumatoid arthritis (RA) who are treated to target. METHODS: Patients with newly diagnosed RA participating in the Behandel-Strategieën, "treatment strategies" (BeSt) study (n=508) were followed for median 10 years while receiving Disease Activity Score (DAS) ≤2.4 steered treatment. Every 3 months 68 joints were assessed for the presence of swelling. We evaluated whether baseline local joint swelling was predictive for swelling in the same joint during follow-up using a multilevel mixed-effect logistic regression model. Different strategies were used to account for missing data. A permutation test was performed to assess if joint swelling was better predicted by baseline swelling of the joint itself than by baseline swelling of randomly selected other joints. RESULTS: In 46% of the joints that were swollen at baseline, joint swelling later recurred at least once during follow-up. Joint swelling at baseline was statistically significantly associated with swelling in the same joint during follow-up (OR 2.37, 95% CI 2.30 to 2.43, p<0.001), and also specifically with recurrent swelling in the same joint (OR 1.73, 95% CI 1.37 to 1.59, p<0.001). Local joint swelling was better predicted by baseline swelling of that particular joint than by baseline swelling of other joints (p<0.001). CONCLUSION: Joint swelling tends to recur locally in the joints swollen at RA onset. This suggests that local factors influence the manifestation of joint inflammation over time.
33004534 Tofacitinib Persistence in Patients with Rheumatoid Arthritis: A Retrospective Cohort Stud 2021 Jan 1 OBJECTIVE: To compare medication persistence of tofacitinib with persistence of injectable biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA). METHODS: We performed a retrospective new-user cohort study of patients with RA in the IBM MarketScan Research Databases. New users of tofacitinib or bDMARD were identified between November 2012 and December 2016. Persistence, in number of years, was the time between treatment initiation and the earliest occurrence of discontinuation or switching from the medication prescribed at cohort entry. Persistence of tofacitinib was compared with bDMARD persistence using Cox proportional hazards regression with adjustment for high-dimensional propensity scores. Similar methods were used for an analysis of post first-line therapy in patients who switched to tofacitinib from a bDMARD. RESULTS: New tofacitinib users (n = 1031) were 56 years of age, on average, and 82% were women. New bDMARD users (n = 17,803) were 53 years of age, on average, and 78% were women. New tofacitinib users had shorter medication persistence (median 0.81 yrs) compared to bDMARD patients (1.02 yrs). After adjustment, the HR for discontinuation of tofacitinib compared with bDMARD was 1.14 (95% CI 1.05-1.25). Patients who switched to tofacitinib from a bDMARD had longer persistence than patients who switched to a bDMARD (adjusted HR for discontinuation 0.90, 95% CI 0.83-0.97). CONCLUSION: Further research is warranted to understand the reasons for discontinuation of tofacitinib despite its ease of administration and to understand the observed differences between switchers and new users.
33540963 [Clinical characteristics and prognosis of sudden sensorineural hearing loss with rheumato 2021 Jan 5 Objective:To analyze the clinical features and prognosis of sudden sensorineural hearing loss（SSNHL） with rheumatoid arthritis（RA）, and evaluate the effect of the course of RA on the hearing recovery. Methods:We collected the clinical data of 43 SSNHL patients（46 ears） with RA（RA group） who were hospitalized in our hospital, and compared their clinical characteristics and prognosis with 386 SSNHL patients（400 ears） without RA（non-RA group）. 43 SSNHL patients with RA were further grouped into <5 years group, 5-10 years group and >10 years group, and the hearing recovery was compared among three groups. Results:In the RA group, the initial pure tone average（PTA） of SSNHL and non-SSNHL ears were （64.53±12.77） dB HL and （31.28±8.53） dB HL, which were higher than those in the non-RA group（54.31±13.45） dB HL and（24.83±6.06） dB HL（P<0.05）. After treatment, in the RA group, posttreatment PTA of SSNHL and non-SSNHL ears were （48.26±13.49） dB HL and （27.93±10.22） dB HL, which were higher than those in the non-RA group （33.65±9.22） dB HL and （21.86±6.88） dB HL（P<0.05）, and the hearing gains of SSNHL ear and the rate of overall recovery were （16.27±6.01） dB HL and 52.17%, which were lower than those in the non-RA group （20.66±6.21） dB HL and 75.00%. No statistic difference was observed in the hearing gains of non-SSNHL ear between the two groups（P>0.05）. The hearing gains in the <5 years group, 5-10 years group and >10 years group were （20.77±8.63） dB HL, （17.00±6.81） dB HL and （11.94±5.73） dB HL, statistic differences were observed among the three groups（P=0.010）, but no statistic difference was observed in the rate of complete recovery, marked recovery, recovery and no recovery（P>0.05）. Conclusion:SSNHL patients with RA often suffers a severe hearing loss, and the hearing recovery is poor. The longer the course of RA, the worse the prognosis.
33277938 Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection. 2021 Mar Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.
32475009 Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice. 2021 Sep OBJECTIVE: To show the safety and efficacy of subcutaneous (SC) methotrexate (MTX) compared to oral MTX, alternative disease-modifying antirheumatic drugs (DMARDs) monotherapy, biologic monotherapy, and combinations (conventional and biologic combination groups) in routine clinical practice. METHODS: Clinical and laboratory data were retrospectively analyzed for rheumatology clinic attendances at a large Northeast England hospital trust between January 2014 and January 2018. Rates of adverse events and stop events (transaminitis [serum alanine aminotransferase level of >80 units/liter] or neutropenia [neutrophil count of <2.0 × 10(9) /liter]) were calculated, with adjustment for duration of DMARD exposure. RESULTS: In the present study, 8,394 patients received DMARDs, with 2,093 patients receiving oral MTX and 949 patients receiving SC MTX. The median dose was 15 mg (interquartile range [IQR] 10-20 mg) for oral MTX, and 20 mg (IQR 15-25 mg) for SC MTX (P < 0.0001). Continuation rates were higher for SC MTX therapy when adjusted for follow-up duration, with a rate ratio (RR) of 1.54 (95% confidence interval [95% CI] 1.40-1.70) (P < 0.0001). For the time period assessed, 2,382 patients experienced 4,358 adverse events, with 1,711 incidents of transaminitis and 2,647 incidents of neutropenia recorded. Significantly fewer adverse events were observed in patients who received SC MTX monotherapy versus those who received biologic and combination DMARD therapies (P < 0.01). Compared to oral MTX, SC MTX was associated with a nonsignificant trend toward lower rates of neutropenia, but only a slightly higher rate of transaminitis (RR 1.26 [95% CI 1.07-1.48]) (P = 0.006), despite significantly higher doses of MTX. CONCLUSION: Subcutaneous MTX is safe in routine clinical practice. This is the largest study yet reported on SC MTX and provides observational data that SC MTX is continued longer and better tolerated in patients compared to other therapy groups, especially oral MTX.
34774696 Transdermal release of methotrexate by cationic starch/poly(vinyl alcohol)-based films as 2022 Jan 5 Methotrexate (MTX) is a common drug used for rheumatoid arthritis (RA) treatment; however, a series of adverse effects associated with its oral or subcutaneous administration is reported. Transdermal delivery of MTX is an alternative to abate these issues, and the use of drug delivery systems (DDS) based on polymeric films presents an impressive potential for this finality. Based on this, in this study, we report the preparation of films made by cationic starch (CSt), poly(vinyl alcohol) (PVA), and chondroitin sulfate (ChS) to incorporate and release MTX, as well as the in vivo evaluation in model of rheumatoid arthritis in mice. CSt/PVA and CSt/PVA/ChS-based films (with and without MTX) were prepared using a simple protocol under mild conditions. The films loaded with 5 w/w-% of MTX exhibited appreciable drug loading efficiency and distribution. The MTX permeation through the layers of porcine skin demonstrated that most of the drug permeated was detected in the medium, suggesting that the formulation can provide a systemic absorption of the MTX. In vivo studies performed in an arthritis-induced model in mice demonstrated that the MTX-loaded films were able to treat and attenuate the symptoms and the biochemical alterations related to RA (inflammatory process, oxidative stress, and nociceptive behaviors). Besides, the pharmacological activity of MTX transdermally delivery by the CSt/PVA and CSt/PVA/ChS films was comparable to the MTX orally administered. Based on these results, it can be inferred that both films are prominent materials for incorporation and transdermal delivery of MTX in a practical and non-invasive manner.
34915341 Omega 3 polyunsaturated fatty acids: Potential anti-inflammatory effect in a model of ovar 2022 Feb OBJECTIVE: To evaluate the effect of polyunsaturated fatty acid-type omega 3 (ω3) on the temporomandibular joint (TMJ) of ovariectomized rats (OVX) with rheumatoid arthritis (RA). DESIGN: Rheumatoid arthritis was induced using complete Freund's adjuvant and type II bovine collagen injected at the base of the tail. Twenty-four adult female rats were treated by gavage and divided into four groups: G1: Sham, treated with 0.9% NaCl; G2: OVX, treated with 0.9% NaCl; G3: OVX+RA treated with 0.9% NaCl; G4: OVX+RA+ω3 treated with omega 3 (300 mg/kg/day). The induction of rheumatoid arthritis in groups G3 and G4 was performed 21 days after OVX, treatments were started 15 days after the induction of rheumatoid arthritis, maintained for 7 days, and killed. Bilateral TMJs were removed and assigned to morphometric analysis by micro-computed tomography and immunoassay to assess levels of cytokines IL-1β, IL-6, TNF-α, and IL-10. RESULTS: Higher levels of inflammatory cytokines were found in the G2 and G3 (P < 0.05) and anti-inflammatory cytokines in the G1 and G4. TMJ analysis by micro-computed tomography showed a higher percentage of bone volume (median - interquartile deviation) in G1 (96.2-1.1) than in the G2 (91.5-2.0, P = 0.0374) and G3 (85.1-5.2, P = 0.0001) but showed no statistically significant differences with the G4 (93.1-1.7, P = 0.79). CONCLUSIONS: Omega 3 successfully reduced TMJ damage in rats caused by ovariectomy and induced rheumatoid arthritis, and is a promising alternative for bone repair and attenuation of inflammatory processes.
33704594 High serum IgA and activated Th17 and Treg predict the efficacy of abatacept in patients w 2021 Sep OBJECTIVE: To identify the predictive biomarkers for achieving remission with abatacept in patients with seropositive rheumatoid arthritis (RA). METHODS: We enrolled patients with RA who were treated with abatacept. We compared the baseline laboratory results and longitudinal immune-phenotyping data between patients who achieved remission and those who did not achieve remission at 6 months according to the clinical disease activity index. RESULTS: One hundred and twenty RA patients were enrolled. In the seropositive patients with early RA (n = 24), high serum IgA levels, anti-citrullinated peptide (CCP) titers, and neutrophil counts before treatment were predictors of remission (area under the curve [AUC], 0.659, 0.741, and 0.704, respectively). Additionally, activated Th17 (aTh17) cells and activated Treg (aTreg) cells before treatment were found to be significantly higher in patients with remission compared to those without remission (2.9% vs 1.1%, P = 0.02; 34.3% vs 17%, P = 0.03, respectively). The measurement of longitudinal cell subpopulation revealed a decrease in the effector CD4 T cell population after abatacept treatment, which correlated with anti-CCP titers and neutrophil counts, and was associated with remission achievement. In seropositive patients with established RA (n = 79), high RF titers and low IFN-γ levels were associated with the good response to abatacept. CONCLUSION: Our study has shown that serum IgA levels, anti-CCP titer, and neutrophil counts are predictive biomarkers for predicting the response to abatacept in patients with seropositive and early RA and may reflect the inhibition of effector CD4 T cell subpopulations by abatacept. Key Points • Serum IgA levels and neutrophil counts are novel biomarkers for predicting the efficacy of abatacept. • Those may reflect the inhibition of effector CD4 T cell subpopulations by abatacept.
34142326 Towards Personalising the Use of Biologics in Rheumatoid Arthritis: A Discrete Choice Expe 2022 Jan INTRODUCTION: There have been promising developments in technologies and associated algorithm-based prescribing ('stratified approach') to target biologics to sub-groups of people with rheumatoid arthritis (RA). The acceptability of using an algorithm-guided approach in practice is likely to depend on various factors. OBJECTIVE: This study quantified preferences for an algorithm-guided approach to prescribing biologics (termed 'biologic calculator'). METHODS: An online discrete choice experiment (DCE) was designed to elicit preferences from patients and the public for using a 'biologic calculator' compared with conventional prescribing. Treatment approaches were described by five attributes: delay to starting treatment; positive and negative predictive value (PPV/NPV); risk of infection; and cost saving to the UK national health service. Each survey contained six choice sets asking respondents to select their preferred option from two hypothetical biologic calculators or conventional prescribing. Background questions included sociodemographics, health status and healthcare experiences. DCE data were analysed using mixed logit models. RESULTS: Completed choice data were collected from 292 respondents (151 patients with RA and 142 members of the public). PPV, NPV and risk of infection were the most highly valued attributes to respondents deciding between prescribing strategies. CONCLUSION: Respondents were generally receptive to personalised medicine in RA, but researchers developing personalised approaches should pay close attention to generating evidence on both the PPV and the NPV of their technologies.
33550047 'Methyl palmitate attenuates adjuvant induced arthritis in rats by decrease of CD68 synovi 2021 May The study was designed to investigate the potential anti-arthritic effects of methyl palmitate in an adjuvant arthritis model in rats that shares many histopathological similarities with human RA. The underlying mechanism and its effect on CD68 macrophages were investigated, as a further argument to its possible efficacy in RA treatment. A normal control group was injected only with saline, arthritic group, and three treatment groups with CFA induced arthritis received methyl palmitate (MP) at three different doses (75, 150, 300 mg/kg/week for 3 weeks, intraperitoneal). The degree of ipsilateral paw swelling, ankle diameter, spleen index, thymus index and the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β were measured. In addition, the underlying molecular mechanism was investigated using CD68 expression. Methyl palpitate significantly and dose dependently decreased the arthritic symptoms as measured by ipsilateral paw volume and ankle diameter. It showed no effect on body weight but significantly decreased splenic, thymus index, serum TNF-α and IL-1β. CD68 macrophages expression and the overall synovial inflammatory cellularity were halted. Methyl palmitate exhibits significant anti-inflammatory and exerts a potential anti-arthritic effect in a rat model of adjuvant induced arthritis. Furthermore, it inhibits expression of synovial CD68 macrophage that validate its therapeutic potential adjuvant arthritis.
32964298 Comparison of the analytical and clinical performances of four anti-cyclic citrullinated p 2021 Feb INTRODUCTION/OBJECTIVES: Anti-cyclic citrullinated peptide antibody (anti-CCP) is one of the most important serologic markers for diagnosing rheumatoid arthritis (RA). This study aimed to compare the analytical and clinical performances of the second- and third-generation anti-CCP assays. METHODS: Four automated anti-CCP assays were evaluated: Chorus anti-CCP (Diesse Diagnostica), Elecsys anti-CCP (Roche Diagnostics), Atellica® IM anti-CCP IgG (Siemens Healthineers), and Quanta Flash® CCP3 (Inova Diagnostics Inc.). Analytical performance included the precision, linearity, correlation, and concordance rate. For evaluating the clinical performance, 240 patient samples (120 positive and 120 negative samples, determined by the Chorus anti-CCP assay) were used, including those with a diagnosis of RA (n = 132) and non-RA (n = 108). Using receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity were evaluated. RESULTS: All four assays that were evaluated showed good precision and linearity, and their correlation and concordance rates were in acceptable ranges. The area under the curve (AUC) values ranged from 0.888 to 0.914, showing a good diagnostic performance. The sensitivity and specificity of all assays were similar (88.0-97.2%). CONCLUSIONS: All four anti-CCP assays showed good analytical and diagnostic performances for diagnosing RA. After adjusting the cutoff values, these assays are expected to show enhanced sensitivity and specificity. Key Points • Previous studies have described the diagnostic performance of a few immunologic markers in RA diagnosis, but nothing has been proven to be sufficiently good in clinical practice. • All four automated anti-CCP assays showed good analytical and diagnostic performances for diagnosing RA in clinical practice. • After adjusting the cutoff values, these assays are expected to show enhanced sensitivity and specificity. • The present study provides reassuring evidence that any of the studied commercially available anti-CCP tests for detecting rheumatoid arthritis provide similar diagnostic information to institutions that adopt these specific testing systems.
33612101 A meta-analysis of HDL cholesterol efflux capacity and concentration in patients with rheu 2021 Feb 21 BACKGROUND: Poor cholesterol efflux capacity (CEC) has been proposed to be an independent risk factor for cardiovascular diseases. However, current evidence is inconsistent, especially in rheumatoid arthritis (RA) patients. This meta-analysis aims to identify whether CEC is impaired or altered by drug therapy in RA. METHODS: The PubMed/MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases were browsed to identify studies on CEC in RA patients. The searches mainly focused on studies in human subjects that were published before November 14, 2020, without any language restrictions. The effect size was pooled by the standardized mean differences and mean differences (SMD & MD) as well as the corresponding 95% confidence intervals (CIs) in a random or fixed effect model. Heterogeneity across the studies was tested using Cochran's Q test and I(2) statistic. Newcastle-Ottawa Scale and the Downs and Black scale (D&B) were applied to evaluate the quality of included studies. The GRADE-system with its 4-grade evidence scale was used to assess the quality of evidence. RESULTS: A total of 11 eligible articles, including 6 observational and 5 interventional studies, were retrieved. The pooled results showed that in patients with RA, CEC was not significantly different than in healthy controls (SMD: -0.34, 95% CI: - 0.83 to 0.14), whereas the plasma HDL-C levels was significantly lower (MD: -3.91, 95% CI: - 7.15 to - 0.68). Furthermore, in the before-after studies, the CEC of RA patients (SMD: 0.20, 95% CI: 0.02 to 0.37) increased, but the plasma HDL-C levels (MD: 3.63, 95% CI: - 0.13 to 7.39) remained at a comparable quantity after anti-rheumatic treatment comparing with the baseline. In addition, the funnel plot of included studies displayed a lightly asymmetry, while Egger's and Begg's test did not suggest the existence of publication bias. The quality of evidence was rated according to GRADE as moderate to very low. CONCLUSION: The current meta-analysis demonstrated that HDL-mediated CEC can be improved by the early control of inflammation and anti-rheumatic treatment in RA patients, which is independent of the plasma HDL-C levels. However, the results should be interpreted with caution because of low-quality and limited quantity of evidence. Future randomized controlled trials are needed to determine whether therapeutic strategies to enhance CEC in RA patients have beneficial effects for preventing CVD.
34423050 Citrullinated Antigens with Multiple Citrulline Similar Motif in the Diagnosis of Rheumato 2021 The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.
34596590 Association of Three Functional Polymorphisms in the NLRP3 Gene with Susceptibility to Rhe 2021 Sep BACKGROUND: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA. OBJECTIVE: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk. METHOD: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real‑time polymerase chain reaction high‑resolution melting (HRM) method. RESULTS: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05). CONCLUSION: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.
34569543 PhosSNPs-Regulated Gene Network and Pathway Significant for Rheumatoid Arthritis. 2021 OBJECTIVES: Peripheral blood mononuclear cells (PBMCs) are critical for immunity and participate in multiple human diseases, including rheumatoid arthritis (RA). PhosSNPs are nonsynonymous SNPs influencing protein phosphorylation, thus probably modulate cell signaling and gene expression. We aimed to identify phosSNPs-regulated gene network/pathway potentially significant for RA. METHODS: We collected genome-wide phosSNP genotyping data and transcriptome-wide mRNA expression data from PBMCs of a Chinese sample. We discovered and verified with public datasets differentially expressed genes (DEGs) associated with RA, and replicated RA-associated SNPs in our study sample. We performed a targeted expression quantitative trait locus (eQTL) study on significant phosSNPs and DEGs. RESULTS: We identified 29 nominally significant eQTL phosSNPs and 83 target genes, and constructed comprehensive regulatory/interaction networks, highlighting the vital effects of two eQTL phosSNPs (rs371513 and rs4824675, FDR <0.05) and four critical node genes (HSPA4, NDUFA2, MRPL15, and ATP5O). Besides, two node/key genes NDUFA2 and ATP5O, regulated by rs371513, were significantly enriched in mitochondrial oxidative phosphorylation pathway. Besides, four pairs of eQTL effects were replicated independently in whole blood and/or transformed fibroblasts. CONCLUSIONS: The findings delineated a potential role of protein phosphorylation and genetic variations in RA and warranted the significant roles of phosSNPs in regulating RA-associated genes expression in PBMCs. The results pointed out the relevance and significance of oxidative phosphorylation pathway to RA.