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ID PMID Title PublicationDate abstract
31602546 A Lipid Micellar System Loaded with Dexamethasone Palmitate Alleviates Rheumatoid Arthriti 2019 Oct 10 Glucocorticoids have been confirmed to be effective in the treatment of a variety of inflammatory diseases. However, their application encounters limitations in terms of tissue distribution and bioavailability in vivo. To address these key issues, we designed and developed a nanopreparation by using egg yolk lecithin/sodium glycocholate (EYL/SGC) and utilize such mixed micelles (MMs) to encapsulate dexamethasone palmitate (DMP) for the treatment of rheumatoid arthritis (RA). The prepared DMP-MMs had an average particle size of 49.18 ± 0.43 nm and were compared with an emulsion-based dexamethasone palmitate. Pharmacokinetic and in vivo fluorescence imaging showed that mixed micelles had higher bioavailability and targeting efficiency in inflammatory sites. An arthritis rat model was established via induction by Complete Freund's Adjuvant (CFA), followed by the efficacy studies by the observations of paw volume, histology, spleen index, pro-inflammatory cytokines, and CT images. It was confirmed that intravenous injection of DMP-MMs exhibited advantages in alleviating joint inflammation compared with the emulsion system. Composed of pharmaceutical adjuvants only, the nanoscale mixed micelles seem a promising carrier system for the RA treatment with lipophilic drugs.
31859893 Evaluation of the Health Assessment Questionnaire Disability Index in Chilean patients wit 2019 May BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQDI) is one of the main instruments used to evaluate functional status in rheumatoid arthritis (RA). AIM: To assess the reliability and validity of the Spanish version of HAQDI in Chilean RA population. MATERIALS AND METHODS: The questionnaire was applied to 98 patients with RA aged 44 ± 12 years (90% women). Reliability was assessed using Cronbach's alpha statistic for internal consistency. Construct validity was assessed by comparing total HAQDI value and eight HAQDI domains with multiple parameters of disease activity. Discriminant validity was evaluated by classifying disease activity in low, medium or high and evaluating HAQDI value in each category. Floor and ceiling effects were evaluated. To assess construct validity, principal components analysis was performed using varimax rotation. RESULTS: There were no issues in the comprehensibility of the questionnaire. Mean HAQDI score was 1.57 ± 0.66. Standardized Cronbach's Alpha was 0.883. Correlations between Chilean HAQ domains had a p value less than 0.001, and values ranged from 0.317 to 0.597. Activity parameters, DAS 28 and CDAI were significantly correlated with HAQDI domains. Mean HAQDI values were 0.98 ± 0.59,1.45 ± 0.57, and 1.90 ± 0.56 for mild, moderate and severe disease activity. A principal components analysis identified two factors that accounted for 70.0% of total variability. CONCLUSIONS: This study shows that the Spanish version of HAQDI is reliable and valid and can be used in Chilean patients with RA.
30877218 Identifying Rheumatoid Arthritis Cases within the Quebec Health Administrative Database. 2019 Dec OBJECTIVE: Our objective was to calculate rheumatoid arthritis (RA) point prevalence estimates in the CARTaGENE cohort, as well as to estimate the sensitivity and specificity of our ascertainment approach, using physician billing data. We investigated the effects of using varying observation windows in the Régie de l'assurance maladie du Québec (RAMQ) health services administrative databases, alone or in combination with self-reported diagnoses and drugs. METHODS: We studied subjects enrolled in the CARTaGENE cohort, which recruited 19,995 participants from 4 metropolitan regions in Québec from August 2009 to October 2010. A series of Bayesian latent class models were developed to assess the effects of 3 factors: the number of years of billing data, the addition of self-reported information on RA diagnoses and drugs, and the adjustment for misclassification error. RESULTS: The 3-year 2010 point prevalence estimate among cohort members aged 40-69 years, using physician billing plus self-report, adjusting for misclassification error in each source, was 0.9% [95% credible interval (CrI) 0.7-1.2] with RAMQ sensitivity of 84.0% (95% CrI 74.0-93.7) and a specificity of 99.8% (95% CrI 99.6-100.0). Our results show variations in the prevalence point estimates related to all 3 factors investigated. CONCLUSION: Our study illustrates that multiple data sources identify more RA cases and thus a higher prevalence estimate. RA point prevalence estimates using billing data are lower if fewer years of data are used.
31052493 Discovery of Novel Potential Reversible Peptidyl Arginine Deiminase Inhibitor. 2019 May 2 Citrullination, a posttranslational modification, is catalyzed by peptidylarginine deiminases (PADs), a unique family of enzymes that converts peptidyl-arginine to peptidyl-citrulline. Overexpression and/or increased PAD activity is observed in rheumatoid arthritis (RA), Alzheimer's disease, multiple sclerosis, and cancer. Moreover, bacterial PADs, such as Porphyromonas gingivalis PAD (PPAD), may have a role in the pathogenesis of RA, indicating PADs as promising therapeutic targets. Herein, six novel compounds were examined as potential inhibitors of human PAD4 and PPAD, and compared to an irreversible PAD inhibitor, Cl-amidine. Four of the tested compounds (compounds 2, 3, 4, and 6) exhibited a micromolar-range inhibition potency against PAD4 and no effect against PPAD in the in vitro assays. Compound 4 was able to inhibit the PAD4-induced citrullination of H3 histone with higher efficiency than Cl-amidine. In conclusion, compound 4 was highly effective and presents a promising direction in the search for novel RA treatment strategies.
30948137 Cricoarytenoid joint abscess associated with rheumatoid arthritis. 2019 May Cricoarytenoid joint arthritis is an uncommon manifestation of rheumatoid arthritis. We encountered a 68-year-old woman with rheumatoid arthritis who presented with odynophagia, dysphagia, and progressive shortness of breath. Examination findings showed diminished mobility of the left vocal cord and right arytenoid swelling associated with an immobile right vocal cord. Computed tomography (CT) imaging identified a ring-enhancing lesion of the right lateral cricoarytenoid joint. Microdirect laryngoscopy with drainage of the cricoarytenoid abscess and tracheotomy were performed. Development of a laterally based cricoarytenoid joint abscess is identified as a complication of chronic rheumatoid arthritis with successful management described.
31527613 Study of vertebral fracture and Scanographic Bone Attenuation Coefficient in rheumatoid ar 2019 Sep 16 The objective of this study is to identify the prevalence of vertebral fractures (VFs) and to measure the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) based CT-scan, a biomarker of bone fragility in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and in a control group. This monocentric and retrospective study included patients with RA and AS, based on ACR/EULAR or New-York criteria, respectively. A control group was constituted. All of the patients received a CT-scan. VFs were determined via CT-scans according to the Genant classification, and the SBAC-L1 was measured in Hounsfield units (HU). SBAC-L1 ≤145 HU (fracture threshold) defined patients at risk of VFs. 244 patients were included (105 RA, 83 AS, 56 controls). Of the 4.365 vertebrae studied, 66 osteoporotic VFs were found in 36 patients: 18 (17.1%) RA, 13 (15.7%) AS and 5 (8.9%) controls. The mean SBAC-L1 was 142.2 (±48.4) HU for RA, 142.8 (±48.2) for AS, both of which were significantly lower than that of the control group (161.8 (±42.7) HU). Of the 36 patients with VFs and rheumatism, 28% had a T-score ≤-2.5 SD and 71.4% a SBAC-L1 ≤145 HU. A T-score ≤-2.5 SD and a SBAC-L1 ≤145 HU were associated with VF (OR = 3.07 (CI 95%: 1.07; 8.81), and 2.31 (CI 95%: 1.06; 5.06)), respectively. The SBAC-L1 was significantly lower in the RA and AS groups than in the control group. Furthermore, SBAC-L1 ≤145 HU was associated with a higher risk of VFs, with an odds ratio similar to that of a DXA.
30892636 The autoantibody response to cyclic citrullinated collagen type II peptides in rheumatoid 2019 Sep 1 OBJECTIVES: The detection of anti-citrullinated peptide antibodies (ACPAs) is a serological hallmark of RA. Autoantibodies reactive with collagen type II (CII) are present in RA sera and synovial fluid and are potentially pathogenic. Here, we investigate the prevalence and specificity of the autoantibody responses to defined citrullinated cyclic peptides derived from CII in a China RA cohort. METHODS: Using bead-based multiplex assay, we examined the presence of autoantibodies binding to 54 cyclic 17-mer citrullinated CII peptides, encompassing all citrullinate epitopes in CII, and the corresponding unmodified peptides in 415 RA patients, in addition to 304 patients with OA. Furthermore, the autoantibody responses to a selected set of 10 cyclic citrullinated peptides were also examined in 203 healthy individuals. RESULTS: Autoantibody responses to cyclic citrullinated CII peptides were higher in RA patients as compared with OA patients or healthy individuals, whereas little or negligible antibody responses to cyclic unmodified CII peptides were observed. Interestingly, several novel citrullinated CII epitopes were identified. Antibodies to these novel citrullinated CII epitopes showed not only substantial overlapping reactivities but also had unique specificities. CONCLUSION: We found a high prevalence of autoantibodies against cyclic citrullinated CII in the sera of patients in a China RA cohort. The present study revealed heterogeneous binding patterns against novel citrullinated CII epitopes, which may help to stratify RA patients into different subgroups.
30641659 [The prevalence of latent tuberculosis infection in patients with inflammatory arthritis a 2019 Jan 1 Objective: To investigate the prevalence of latent tuberculosis infection (LTBI) in patients with inflammatory arthritis, and to compare the efficacy of tuberculin skin test (TST) and QuantiFERON-TB Gold (QFT) in screening for LTBI in these patients. Method: Medical records of 149 patients with inflammatory arthritis admitted to inpatient of Peking University International Hospital from December 2015 to December 2017 (diagnosis with rheumatoid arthritis, ankylosing spondylitis, sero-negative spondyloarthropathy, psoriatic arthritis, or reactive arthritis) who accepted TST or QFT were collected. The information included gender, age, history of tuberculosis infection, calcifications presence in chest X-ray or chest CT, TST result, QFT result, medication history before test, and biological treatment and all the patients were made a follow-up. Results: The positive rate of TST was 18.2%(14/77) and that of QFT was 27.1%(26/96), and the overall consistency between the two tests was fair. The rate of LTBI diagnosed by QFT was 22.9%(22/96). The positive rate of TST in patients older than 50 years was significantly higher than those younger than 50 years, but there was no significant difference between the two groups screened by QFT. The M-N values in QFT were decreased in both the patients above the age of 50 and in the patients using immunosuppressive agents. A total of 64 patients accepted biological agent therapy, and in those with a positive result of TST or QFT, only 2 cases received anti-LTBI treatment, but the other 14 cases without anti-LTBI treatment. None of them developed active tuberculosis in the following 3-24 months. Conclusion: The prevalence of LTBI in patients with inflammatory arthritis is consistent with that reported in rheumatoid patients, which is higher than in general people. In patients with inflammatory arthritis older than 50 years, especially those accepted immunosuppressive agents therapy, the immunity may be impaired and QFT is more sensitive than TST for screening LTBI.
31557878 Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Oste 2019 Sep 25 The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.
30474471 Relationship between serum-soluble receptor for advanced glycation end products (sRAGE) an 2019 Nov Objective: Considering the important role of serum soluble receptor for advanced glycation end product (sRAGE/RAGE)-ligand system in rheumatoid arthritis (RA), this study aimed to evaluate serum sRAGE levels in RA patients compared to healthy subjects and to assess whether there is an association between sRAGE levels and disease characteristics in RA.Methods: In this cross-sectional study, 60 RA patients according to the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum sRAGE level was measured using ELISA kit.Results: The mean ± SD age of patients and controls was 54.86 ± 11.65 and 50.71 ± 3.72 years, respectively). Serum sRAGE level was significantly higher in RA patients (median [25th and 75th percentiles], 1000.3 [792.00, 1486.8]) compared to healthy controls (median [25th and 75th percentiles], 293.25 [220.35, 364.24]) (p < .001). There was significant difference in serum sRAGE level according to the activity of disease (p < .001). There were significant positive correlations between serum sRAGE level with disease activity (r = 0.67, p < .001), ESR (r = 0.411, p = .001) and CRP (r = 0.273, p = .035). There were no significant correlations between serum sRAGE level with demographic characteristics as well as biochemical measurements including serum creatinine, BUN, RF, and Anti-CCP (p > .05).Conclusions: Our study revealed higher serum sRAGE levels in RA patients compared to healthy controls, which correlated positively with disease activity.
31354714 Cdk5 Deletion Enhances the Anti-inflammatory Potential of GC-Mediated GR Activation During 2019 The suppression of activated pro-inflammatory macrophages during immune response has a major impact on the outcome of many inflammatory diseases including sepsis and rheumatoid arthritis. The pro- and anti-inflammatory functions of macrophages have been widely studied, whereas their regulation under immunosuppressive treatments such as glucocorticoid (GC) therapy is less well-understood. GC-mediated glucocorticoid receptor (GR) activation is crucial to mediate anti-inflammatory effects. In addition, the anti-cancer drug roscovitine, that is currently being tested in clinical trials, was recently described to regulate inflammatory processes by inhibiting different Cdks such as cyclin-dependent kinase 5 (Cdk5). Cdk5 was identified as a modulator of inflammatory processes in different immune cells and furthermore described to influence GR gene expression in the brain. Whether roscovitine can enhance the immunosuppressive effects of GCs and if the inhibition of Cdk5 affects GR gene regulatory function in innate immune cells, such as macrophages, has not yet been investigated. Here, we report that roscovitine enhances the immunosuppressive Dexamethasone (Dex) effect on the inducible nitric oxide synthase (iNos) expression, which is essential for immune regulation. Cdk5 deletion in macrophages prevented iNos protein and nitric oxide (NO) generation after a combinatory treatment with inflammatory stimuli and Dex. Cdk5 deletion in macrophages attenuated the GR phosphorylation on serine 211 after Dex treatment alone and in combination with inflammatory stimuli, but interestingly increased the GR-dependent anti-inflammatory target gene dual-specificity phosphatase 1 (Dusp1, Mkp1). Mkp1 phosphatase activity decreases the activation of its direct target p38Mapk, reduced iNos expression and NO production upon inflammatory stimuli and Dex treatment in the absence of Cdk5. Taken together, we identified Cdk5 as a potential novel regulator of NO generation in inflammatory macrophages under GC treatment. Our data suggest that GC treatment in combination with specific Cdk5 inhibtior(s) provides a stronger suppression of inflammation and could thus replace high-dose GC therapy which has severe side effects in the treatment of inflammatory diseases.
30421104 Comparison of the effects of exercise and anti-TNF treatment on cardiovascular health in r 2019 Feb People with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Both pharmacological treatment and exercise are suggested in the management of CVD risk in RA. This study explored the effects of exercise and anti-TNF treatment on CVD risk in RA. Twenty RA patients (70% female, 50 (10) years) completed a 3-month exercise intervention and 23 RA patients (65% female, 54 (15) years) started anti-TNF treatment. Markers of disease activity, CVD risk, and vascular function were assessed before and after 3-months of intervention/treatment. Both exercise and anti-TNF treatment improved functional ability and fatigue, anti-TNF treatment was more successful in improving inflammation, disease activity, functional ability and pain. Exercise induced a reduction in overall CVD risk and improvement in vascular function, which was significantly different from anti-TNF treatment where no such changes were found. These findings showed that exercise and anti-TNF had differential effects on CVD risk in RA, and should be combined for optimal CVD risk reduction. Whereas anti-TNF treatment is likely to impact on CVD risk through reducing the systemic inflammatory load, exercise should be recommended to people with RA as an effective self-management strategy to reduce CVD risk further. Once RA patients have responded successfully to anti-TNF treatment, increasing exercise should be encouraged to reduce the risk for CVD. Thus, supporting exercise programmes when the disease is controlled, is likely to enhance the uptake and the maintenance of exercise, which will result in additional benefits to cardiovascular health and wellbeing in people with RA.
30729702 Impact of hepatitis C treatment on pain intensity, prescription opioid use and arthritis. 2019 Apr OBJECTIVE: To assess the impact of direct acting anti-viral (DAA) therapy for hepatitis C virus (HCV) infection on changes in pain intensity and prescription opioid use among Veterans. METHODS: We conducted a retrospective cohort study of Veterans with HCV who were seen in a rheumatology clinic at least once while receiving DAA therapy between January 1, 2010 and December 31st 2016. Demographic characteristics, HCV status, HCV treatment characteristics, numeric rating scale (NRS) pain scores and opioid prescription data were extracted from the electronic medical record. Pain scores were averaged over 6 months prior to HCV treatment and 6 months after completion of treatment. Prescription opioid dose was converted to a morphine equivalent daily dose (MEDD) and averaged across the two 6-month intervals. Generalized estimating equations were used to model the change in average pain and MEDD from pre- to post-HCV treatment. Effect size was assessed using Cohen's d. RESULTS: A total of 121 Veterans, 91% male with average age of 59 were included. Average pre-treatment pain was 4.4 (SD 2.4). The average reduction in pain scores was 0.6 points (P = 0.02, Cohen's d = 0.22) after treatment. Among 67 patients prescribed chronic opioid therapy at baseline, average pre-treatment MEDD was 52.4 mg (SD = 62.5 mg) and post-DAA treatment average MEDD was 49.5 mg (SD = 69.3 mg), representing a decrease by 2.9 mg (P < 0.01, Cohen's d = 0.14). Opioid dose reduction was seen in 43/67 patients and 12 patients discontinued opioids entirely. CONCLUSION: Among US Veterans, subjective pain scores had modest improvement and opioid prescriptions were mildly reduced following treatment with DAA.
30904831 MRI inflammation of the hand interosseous tendons occurs in anti-CCP-positive at-risk indi 2019 Jun Interosseous tendon inflammation (ITI) has been described in rheumatoid arthritis (RA). Whether ITI occurs in at-risk individuals before the onset of clinical synovitis is unknown. OBJECTIVES: To investigate, by MRI, ITI in anti-cyclic citrullinated peptide (CCP)-positive at-risk individuals (CCP +at risk) and to describe the anatomy, prevalence and clinical associations across the RA continuum. METHODS: Hand MRI was performed in 93 CCP + at risk, 47 early RA (ERA), 28 established 'late' RA (LRA) and 20 healthy controls (HC) and scored for ITI, flexor tenosynovitis (TSV) and RA MRI scoring at the metacarpophalangeal joints (MCPJs). Cadaveric and histological studies were performed to explore the anatomical basis for MRI ITI. RESULTS: The proportion of subjects with ITI and the number of inflamed interosseous tendons (ITs) increased along the disease continuum (p<0.001): 19% of CCP +at risk, 49% of ERA and 57% of LRA had ≥1 IT inflamed . ITI was not found in any HC. ITI was more frequently identified in tender MCPJs compared with nontender MCPJs (28% vs 12%, respectively). No IT tenosynovial sheath was identified in cadavers on dissection or histological studies suggesting MRI findings represent peritendonitis. Dye studies indicated no communication between the IT and the joint. CONCLUSIONS: ITI occurs in CCP + at-risk individuals and can precede the onset of clinical synovitis. The ITs may be important nonsynovial extracapsular targets in the development and progression of RA.
31416926 T2 Mapping as a New Method for Quantitative Assessment of Cartilage Damage in Rheumatoid A 2020 Jun 1 OBJECTIVE: Rheumatoid arthritis (RA) is associated with damage of the articular cartilage and the periarticular bone. While imaging of bone damage has substantially improved in recent years, direct imaging of the articular cartilage of the hand joints in patients with RA is still challenging. The study used T2 mapping of the finger joints to assess cartilage damage in RA. METHODS: Magnetic resonance imaging (MRI) at 3 Tesla was done in 30 patients with RA, and T2 relaxation times visualizing alteration in the collagen network and hydration of articular cartilage were mapped in 6 cartilage regions of the metacarpophalangeal (MCP) joints 2 and 3. Values were related to autoantibody status [anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF)], disease duration, and disease activity as well as sex and age of the patients. RESULTS: T2 relaxation times could be reliably measured in the 6 regions of the MCP joints. Significantly higher relaxation times indicating more advanced cartilage alterations were observed in the metacarpal heads of ACPA-positive (p = 0.001-0.010) and RF-positive patients (p = 0.013-0.025) as well as those with longer disease duration (> 3 yrs; p = 0.028-0.043). Current disease activity, sex, and age did not influence T2 relaxation times. CONCLUSION: These data show that cartilage damage can be localized and quantified in the hand joints of patients with RA by T2 mapping. Further, ACPA and RF positivity as well as disease duration appear to be the crucial factors influencing cartilage damage.
32281967 Obesity, metabolic syndrome and other comorbidities in rheumatoid arthritis and psoriatic 2019 Oct In obesity, especially if visceral, and in rheumatic diseases, the production of pro-inflammatory cytokines contributes to an increased cardiovascular risk. Moreover, classic cardiovascular risk factors are more common in these patients. We intended to assess the influence of body mass index (BMI), abdominal circumference (AC) and metabolic syndrome (MS) on disease activity and quality of life in Rheumatoid Arthritis (RA) and Psoriatic Arthritis patients and to compare the results between the RA and PsA patients. We performed a cross-sectional study, including 150 patients with RA and 75 patients with PsA. PsA patients had significantly higher BMI, AC and total of comorbidities than RA patients . Independently the underlying pathology (RA or PsA), the number of comorbidities was correlated positively with DAS28, HAQ , CRP and ESR. In RA group, overweight/obesity (BMI≥25kg/m2) were associated with at least one painful joint and the risk of having at least one swollen joint was 3.4 times higher in patients with increased AC. There was an association between the BMI and AC and the CRP value. Patients with BMI≥25 kg/m2 and increased AC had significantly higher DAS28 scores. MS was associated with significantly higher ESR. There was a positive correlation of both BMI and AC with HAQ and also MS was associated with highest HAQ values. In PsA group, patients with BMI≥25kg/m2 had equally more painful joints and higher CRP values. Patients with MS had higher CRP values, more joint pain and higher disease activity according to DAS28. None of the patients with normal BMI had swollen joints, however 20.4% of overweight patients had at least one swollen joint. The number of comorbidities showed to influence inflammatory parameters, disease activity and quality of life. We found that BMI, AC and MS are associated with disease activity, which may be improved by weight reduction and comorbidities control.
30861322 Citrullinated Inhibitor of DNA Binding 1 Is a Novel Autoantigen in Rheumatoid Arthritis. 2019 Aug OBJECTIVE: To explore the intrinsic role of inhibitor of DNA binding 1 (ID-1) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and to investigate whether ID-1 is citrullinated and autoantigenic in RA. METHODS: RA patient serum ID-1 levels were measured before and after infliximab treatment. RA FLS were transfected with a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 construct targeting ID-1 to examine the effects of ID-1 deletion. RA synovial fluid (SF) and homogenized synovial tissue (ST) were immunoprecipitated for ID-1 and measured for citrullinated residues using an enzyme-linked immunosorbent assay and Western blotting. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on in vitro-citrullinated recombinant human ID-1 (cit-ID-1) to localize the sites of citrullination. Normal and RA sera and SF were analyzed by immunodot blotting for anti-citrullinated protein antibodies (ACPAs) to cit-ID-1. RESULTS: RA patient serum ID-1 levels positively correlated with several disease parameters and were reduced after infliximab treatment. RA FLS displayed reduced growth and a robust increase in interleukin-6 (IL-6) and IL-8 production upon deletion of ID-1. ID-1 immunodepletion significantly reduced the levels of citrullinated residues in RA SF, and citrullinated ID-1 was detected in homogenized RA ST (n = 5 samples; P < 0.05). Immunodot blot analyses revealed ACPAs to cit-ID-1 but not to native ID-1, in RA peripheral blood (PB) sera (n = 30 samples; P < 0.001) and SF (n = 18 samples; P < 0.05) but not in normal PB sera. Following analyses of LC-MS/MS results for citrullination sites and corresponding reactivity in immunodot assays, we determined the critical arginines in ID-1 for autoantigenicity: R33, R52, and R121. CONCLUSION: Novel roles of ID-1 in RA include regulation of FLS proliferation and cytokine secretion as well as autoantigenicity following citrullination.
31761888 Nivolumab for Methotrexate-associated Classic Hodgkin's Lymphoma in a Rheumatoid Arthritis 2020 Mar 15 Nivolumab exerts therapeutic activity in patients with classic Hodgkin's lymphoma (CHL) but may cause several types of immune-related adverse events. Some rheumatoid arthritis (RA) patients develop CHL during methotrexate therapy (MTX-CHL); however, the efficacy and safety of nivolumab for these patients remain unclear. A 68-year-old woman was diagnosed with CHL after six years of MTX therapy for RA. The disease did not respond to any type of chemotherapy. Nivolumab was then initiated, and the patient was successfully treated without the reactivation of RA. The reactivation of RA always needs to be considered with the administration of nivolumab.
30515817 HDAC10 upregulation contributes to interleukin 1β-mediated inflammatory activation of syn 2019 Aug Histone deacetylases (HDACs) are important in chronic inflammation, and inflammatory responses affect synovium-derived mesenchymal stem cell (SMSC) function in temporomandibular joint repair. However, the effect of HDACs on SMSC inflammatory activation remains unclear. In this study, temporomandibular joint fibroblast-like synoviocytes obtained from osteoarthritis patients met the minimal mesenchymal stem cell criteria. Interleukin 1β (IL-1β) upregulated IL-6 and IL-8 expression in SMSCs through nuclear factor-κB (NF-κB) pathway activation. IL-6 and IL-8 upregulation were blocked by broad-acting HDAC inhibitors SAHA and LBH589. MC1568 alleviated IL-1β activation of SMSCs, whereas CI994 and FK228 produced a minimal or opposite effect in vitro. We also found HDAC10 was highly associated with localized IL-1β expression in vivo and in vitro. HDAC10 knockdown alleviated IL-1β-mediated SMSC activation and blocked NF-κB pathway activation. Conversely, HDAC10 overexpression promoted IL-6 and IL-8 expression and IL-1β-mediated NF-κB pathway activation. In conclusion, HDAC10 upregulation contributed to IL-1β-mediated inflammatory activation of SMSCs, indicating that HDAC10 may be a novel therapeutic target.
31392628 Alterations of HDL particle phospholipid composition and role of inflammation in rheumatoi 2019 Nov The increased cardiovascular risk in RA (rheumatoid arthritis) cannot be explained by common quantitative circulating lipid parameters. The objective of the study was to characterize the modifications in HDL phosphosphingolipidome in patients with RA to identify qualitative modifications which could better predict the risk for CVD. Nineteen patients with RA were compared to control subjects paired for age, sex, BMI, and criteria of metabolic syndrome. The characterization of total HDL phosphosphingolipidome was performed by LC-MS/MS. RA was associated with an increased HDL content of lysophosphatidylcholine and a decreased content of PC (phosphatidylcholine), respectively, positively and negatively associated with cardiovascular risk. A discriminant molecular signature composed of 18 lipids was obtained in the HDL from RA patients. The detailed analysis of phospholipid species showed that molecules carrying omega-3 FA (fatty acids), notably docosahexaenoic acid (C22:6 n-3), were depleted in HDL isolated from RA patients. By contrast, two PE (phosphatidylethanolamine) species carrying arachidonic acid (C20:4 n-6) were increased in HDL from RA patients. Furthermore, disease activity and severity indexes were associated with altered HDL content of 4 PE and 2 PC species. In conclusion, the composition of HDL phosphosphingolipidome is altered during RA. Identification of a lipidomic signature could therefore represent a promising biomarker for CVD risk. Although a causal link remains to be demonstrated, pharmacological and nutritional interventions targeting the normalization of the FA composition of altered phospholipids could help to fight against RA-related inflammation and CVD risk.