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ID PMID Title PublicationDate abstract
30672256 [Therapeutic effects on rheumatoid arthritis treated with shu-deep needling and bloodletti 2019 Jan 12 OBJECTIVE: To observe the difference in the therapeutic effects on rheumatoid arthritis (RA) between the combined shu-deep needling and bloodletting technique and the regular needling technique. METHODS: A total of 70 patients were randomized into an observation group (35 cases) and a control group (35 cases, 4 cases dropped-out). Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Jinsuo (GV 8), Ganshu (BL 18), Shenshu (BL 23), Zhibian (BL 54), Weizhong (BL 40), Taixi (KI 3) and Tianzong (SI 11), etc. were selected in the two groups. Additionally, in the observation group the shu-deep needling technique was adopted at Tianzong (SI 11) and Zhibian (BL 54), the bloodletting technique at the local swollen area and the even-needling technique at the rest acupoints. In the control group, the even-needling technique was applied to all of the acupoints. Acupuncture treatment was given once every two days, 3 times a week and for 12 weeks totally. The numbers of tender points at the knee joint, the numbers of swollen sites at the knee joint, the visual analogue scale (VAS) score and the American health assessment questionnaire (HAQ) score were observed in the two groups before and after treatment, as well as the changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The American College of Rheumatology (ACR) criteria was adopted to evaluate the therapeutic effects of the two groups. RESULTS: After treatment, the numbers of tender points, the numbers of swollen sites, VAS score and HAQ score were all improved as compared with those before treatment in the two groups (all P<0.01), and the results in the observation group were better than those in the control group (all P<0.05). After treatment, ESR and CRP levels were all reduced as compared with those before treatment in the two groups (all P<0.01), but there was no significant differences between the two groups (both P>0.05). The standard-reaching rates of ACR 20 and ACR 50 in the observation group were 94.3% (33/35) and 31.4% (11/35) respectively, which were better than 67.7% (21/31) and 6.5% (2/31) in the control group (P<0.01, P<0.05). CONCLUSION: The acupuncture with the shu-deep and bloodletting techniques and the acupuncture with regular needling technique are all effective on RA. The therapeutic effects of the acupuncture treatment with the shu-deep and bloodletting techniques are better than that with regular needling technique.
30941596 Ankle pain in rheumatoid arthritis: comparison of clinical and sonographic findings. 2019 Oct To describe the prevalence and distribution of clinical and ultrasound (US) pathological findings at ankle level and to compare them, in patients with rheumatoid arthritis (RA). This is a descriptive, cross-sectional study assessing patients diagnosed with RA according to the 2010 ACR criteria, who were recruited consecutively and independently of disease status or treatment and of the presence of pain at ankle level. Clinical and US findings were acquired by two independent rheumatologists. US assessments were performed according to the EULAR and OMERACT indications. A total of 224 ankles of 112 RA patients were examined. One hundred (89.3%) patients were women and 12 (10.7%) were men, with a mean age of 51 years. RA mean disease duration was 72 months. Ankle spontaneous pain was found in 56.2% of the patients. In 65.2% of the patients, US found at least one pathologic sign indicative of joint and/or tendon pathology. Using grayscale US, joint involvement was more frequently found than tendon pathology (37.5% vs 22.3%). Conversely, no substantial difference was found between the prevalence of power Doppler signal at joint and tendon level. There was a significant correlation between clinical findings and US findings indicative of tibiotalar joint synovitis and peroneal tenosynovitis. In the present study, pain and US pathologic findings at ankle level were described and compared in a cohort of RA patients. Spontaneous pain was found in more than half of the patients and US found joint involvement more prevalent than tendon pathology.
30711693 Ultrasonographic criteria for the diagnosis of erosive rheumatoid arthritis using osteoart 2019 Jul OBJECTIVES: The aims of this study were to compare characteristics of radiography (RX) and ultrasound (US) erosive lesions in rheumatoid arthritis (RA) and osteoarthritis (OA) patients (prevalence, topography and severity), to determine thresholds for the diagnosis of erosive RA based on US and to evaluate the performance of US and RX to establish a diagnosis of erosive RA differentiated from hand OA. METHODS: Patients fulfilling ACR 1987 and/or ACR/EULAR 2010 criteria for RA or ACR hand OA criteria were prospectively included. A modified Sharp erosion score was assessed by two blinded readers and one adjudicator for discordant cases (number of eroded joints ≤ three). Erosions in US were scored on six bilateral joints (MCP2-3, 5; MTP2-3, 5) with a four-grade scale to calculate total US score for erosions (USSe). RESULTS: A total of 168 patients were included: 122 RA (32 early RA < 2 years; 90 late RA ≥ 2 years); 46 OA patients. On RX: 42 RA patients (6 early; 36 late) and 5 OA patients were eroded according to EULAR 2013 definition criteria with sensitivity at 34.4% and specificity at 89.1%. On US, 95 RA patients (21 early; 74 late) and 12 OA patients were eroded. Considering at least two joint facets eroded or at least one joint facet eroded at grade 2 on US, sensitivities were good (68-72.1%) and specificities excellent (89.1-100%). Agreement between RX and US was excellent (90-92%). The positive and negative likehood ratios were respectively 3.16 and 0.73 for radiography and 6.64 and 0.31 for US (for two facets eroded). CONCLUSION: USSe can differentiate RA from OA in erosive disease and detect two times more patients with erosive RA than RX with excellent specificity and agreement.
31291785 Systematic review of the psychometric properties of patient-reported outcome measures for 2019 Nov OBJECTIVE: To identify self-reported outcome measures specific to the foot and ankle in patients with rheumatoid arthritis and to investigate the methodological quality and psychometric properties of these measures. METHOD: A systematic review focusing on patients with rheumatoid arthritis. SETTING: The search was conducted in the PubMed, SCOPUS, CINAHL, PEDro and Google Scholar databases, based on the following inclusion criteria: population (with rheumatoid arthritis) > 18 years; psychometric or clinimetric validation studies of patient-reported outcomes specific to the foot and ankle, in different languages, with no time limit. Two of the present authors independently assessed the quality of the studies located and extracted the relevant data. Terwee's criteria and the COSMIN checklist were employed to ensure adequate methodological quality. RESULTS: Of the initial 431 studies considered, 14 met the inclusion criteria, representing 7,793 patients (56.8 years). These instruments were grouped into three dimensions (pain, perceived health status and quality of life and disability). The time to complete any of the PROMs varies around 15 minutes. PROMs criterias with the worst scores by COSMIN, 92.85% and 85.71% were criterion validity, measurement error, internal consistency and responsiveness. 28.57% of PROMs were compared with the measurement properties. CONCLUSION: the Self-Reported Foot and Ankle Score achieved the highest number of positive criteria (according to Terwee and COSMIN), and is currently the most appropriate for patients with Rheumatoid arthritis.
31934245 The involvement of vocal cords in rheumatoid arthritis: a clinical case. 2019 Rheumatoid arthritis rarely involves the cricoarytenoid joint, symptoms of varying severity ranging from foreign body sensation, fullness or tension in the throat, hoarseness, odynophagia, speech or cough pain to stridor and respiratory distress during bilateral paralysis of the vocal cords. We are reporting a case of rheumatoid arthritis with bilateral involvement of the vocal cords. The diagnosis was clinically made and confirmed by endolaryngoscopy, responding to antirheumatic treatment but coming to the stage of permanent tracheotomy.
31245055 Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic an 2019 OBJECTIVES: To identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD). METHODS: Patients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous antibiotics or followed by death. SIs were categorised by aetiology and site. SI risk was assessed through Cox proportional hazards models. Best models were selected using machine learning Least Absolute Shrinkage and Selection Operator (LASSO) methodology. RESULTS: Among 20 361 patients with RA and 6176 patients with NIRMD, 1600 and 276 first SIs were identified, respectively. Incidence of SIs was higher in RA compared with NIRMD (IRR = 1.5; 95% CI 1.2 to 1.5). The risk persisted after adjusting using the LASSO model (HR 1.7; 95% CI 1.5 to 1.8), but attenuated when additionally adjusted for glucocorticoid use (HR 1.3; 95% CI 1.2 to 1.5). SI risk was significantly higher in RA versus NIRMD for bacterial infections as well as for respiratory, skin, bone, joint, bloodstream infections and sepsis irrespective of glucocorticoid use. Compared with NIRMD, SI risk was significantly increased in patients with RA who were in moderate and high disease activity but was similar to those in low disease activity/remission (p trend < 0.001). CONCLUSIONS: The risk of all SIs, particularly bacterial, respiratory, bloodstream, sepsis, skin, bone and joint infections are significantly increased in patients with RA compared with patients with NIRMD. This infection risk appears to be greatest in those with higher RA disease activity.
30715601 [Multimodal rheumatologic complex treatment of rheumatoid arthritis-a monocentric retrosp 2019 Mar BACKGROUND: Multimodal rheumatologic complex treatment (MRCT, operation and procedures classification system, OPS code 8‑983) is a specific concept of acute inpatient care (DRG I97Z) for treatment of patients with rheumatic diseases, degenerative diseases and/or chronic pain syndromes suffering from exacerbated pain and functional impairment. OBJECTIVE: A monocentric retrospective analysis of the effects of MRCT on pain and functional status in patients with rheumatoid arthritis (RA) was conducted. METHODS: A total of 103 treatment episodes in 75 patients with proven RA who received MRCT between 2014 and 2017 were included in the analysis. The changes in pain intensity were evaluated using a numerical rating scale (NRS), the functional limitations as assessed by the Hanover function questionnaire (FFbH) and the health assessment questionnaire (HAQ) and the disease activity (disease activity score of 28 joints, DAS28) before and after MRCT episodes. In addition, the patient characteristics and the course of the disease were documented and a univariate analysis of the influence of these factors on the parameters activity and function was performed. RESULTS: In patients with RA, the MRCT resulted in a significant amelioration of pain (p < 0.0001), a significant improvement of functional capacity (FFbH p = 0.0013, HAQ p = 0.1396) and a significant reduction of disease activity (DAS28 p < 0.0001). Different aspects of the disease and its previous course (e. g. disease duration, type and number of previous anti-rheumatic drugs, current medication) did not have a significant effect on the response. CONCLUSION: This retrospective monocentric analysis proved the efficacy of MRCT with respect to the inpatient treatment period in a large cohort of RA patients. This treatment concept not only improved pain and function (FFbH) but also significantly reduced the disease activity.
30999933 Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthr 2019 Apr 18 BACKGROUND: Clinical guidelines recommend pneumococcal and tetanus vaccinations in patients with rheumatoid arthritis (RA). Baricitinib is an oral, selective Janus kinase (JAK) 1/JAK 2 inhibitor and is approved for the treatment of moderately to severely active RA in adults in over 50 countries including European countries, the USA, and Japan. This substudy evaluated pneumococcal conjugate and tetanus toxoid vaccine (TTV) responses in patients with RA receiving baricitinib. These vaccines elucidate predominantly T cell-dependent humoral antibody response. METHODS: Eligible RA patients receiving baricitinib 2 mg or 4 mg with or without concomitant methotrexate (MTX) were enrolled in a phase 3 long-term extension trial (RA-BEYOND; ClinicalTrials.gov, NCT01885078) in USA/Puerto Rico. Patients were vaccinated with 13-serotype pneumococcal conjugate vaccine (PCV-13) and TTV. Primary endpoints were the proportion of patients achieving a satisfactory humoral response for PCV-13 (≥ 2-fold increase in anti-pneumococcal antibody concentrations in ≥ 6 serotypes) and TTV (≥ 4-fold increase in anti-tetanus concentrations) at 5 weeks post-vaccination. Secondary endpoints included humoral responses at 12 weeks and functional responses of serotypes 4, 6B, 14, and 23F (twofold and fourfold increases in opsonic indexes at 5 and 12 weeks). RESULTS: Of 106 patients with a mean duration of RA of approximately 12 years, 80% were female, 30% were taking corticosteroids, and 89% (N = 94) were taking baricitinib plus MTX; most patients (97% PCV-13/96% TTV) completed the evaluations. Overall, 68% (95% CI 58.4, 76.2) of patients achieved a satisfactory response to PCV-13, 43% (34.0, 52.8) achieved a ≥ 4-fold increase in anti-tetanus concentrations, and 74% (64.2, 81.1) achieved a ≥ 2-fold increase. PCV-13 response was similar for patients taking corticosteroids (71%; 53.4, 83.9) vs those not (67%; 55.2, 76.5). The percentage of sera with a ≥ 2-fold increase in post-vaccination opsonic indexes at week 5 ranged from 47% (serotype 14) to 76% (serotype 6B). Through 12 weeks post-vaccination, seven patients (6.6%) reported injection-site events. There were no deaths during the substudy, and three patients experienced a serious adverse event. CONCLUSIONS: Approximately two thirds of patients on long-term baricitinib achieved satisfactory humoral and functional responses to PCV-13 vaccination, while TTV responses were less robust. PCV-13 response was not diminished in those taking concomitant corticosteroids. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01885078 . Registered on 24 June 2013.
31470891 CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis 2019 Aug 30 BACKGROUND: Recent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA). METHODS: In a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients. RESULTS: In the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015). In RA patients, the proportion of CCR6+ ILCs in SF was positively correlated with tender joint counts (TJC) and swollen joint counts (SJC) (ρ=0.689, p = 0.0032 and ρ=0.644, p = 0.0071, respectively). Levels of CC chemokine ligand 20 (CCL20) increased in SF of patients with RA and were significantly correlated with CCR6+ ILC number (ρ=0.697, p = 0.0001). CONCLUSION: CCR6+ ILC3s may play some roles in the development of RA through the production of IL-17 and IL-22.
30398699 Dose reduction of biologic therapy in inflammatory arthritis: A qualitative study of patie 2019 Mar OBJECTIVE: Successful biologic disease-modifying anti-rheumatic drug (bDMARD) dose reduction appears increasingly possible from clinical trials. The present study aimed to understand the patient perspective of bDMARD dose reduction. METHODS: Patients with rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis who were self-administering subcutaneous bDMARDs therapy at two National Health Service trusts participated in semi-structured interviews. To capture multiple experiences, patients were purposefully sampled for a range of age, gender, disease duration, reducing/not reducing bDMARDs and either within 3-12 months of bDMARD initiation or ≥12 months and in remission/low disease activity. Inductive thematic analysis was utilized. RESULTS: Fifteen patients were interviewed (six on dose reduction). Five overarching themes were identified. When thinking about dose reduction, patients reflected on their difficult life before bDMARDs ("Where I was then") compared with their transformative effects ("Where I am now"). All raised concerns that a dose reduction would take them back to where they used to be ("Fears for the future") and most believed it to be a cost-cutting exercise. Most had "Hopes for the future", that a reduction would lower their risk of side effects, and release funds for other patients. They wanted a clear rationale for reduction, collaborative decision making, and control over flexible dosing ("Information needs"). CONCLUSION: Patients were fearful of reducing the dose of their bDMARDs, having previously experienced uncontrollable symptoms. However, most were willing to try, provided that there was a clear rationale and that it was in their best interests, with opportunities for collaboration and dose control. These patient perspectives will inform the provision of patient information to guide clinical discussions.
30740244 Cotreatment with methotrexate in routine care patients with rheumatoid arthritis receiving 2019 OBJECTIVES: We aimed to evaluate the effects of methotrexate (MTX) comedication added to biological disease-modifying antirheumatic drugs (bDMARD) on disease activity measures in patients with rheumatoid arthritis (RA) in routine care. METHODS: Patients with RA on treatment with either bDMARDs or conventional synthetic DMARDs were included in this prospective cohort study. The effect of (time-varying) combination therapy with bDMARD and MTX compared with bDMARD monotherapy was tested in longitudinal generalised estimating equation models using as outcomes: (1) the likelihood to be in remission according to the 28-joint Disease Activity Score (DAS28) erythrocyte sedimentation rate (ESR) (<2.6) and to the Routine Assessment of Patient Index Data 3 (RAPID3) (0-30; ≤3), a patient-reported outcome measure about RA symptoms; and (2) DAS28-ESR and RAPID3 as continuous variables. All models were adjusted for potential confounders: age, gender, drugs for comorbidities (yes/no), oral steroids (yes/no) and non-steroidal anti-inflammatory drug (yes/no). RESULTS: In total, 330 patients were included (mean (SD) follow-up; 10.7 (9.7) months). Compared with bDMARD monotherapy, MTX combination therapy was significantly associated with a 55% higher likelihood to be in DAS28 remission, but not RAPID3 remission, over time. Combination therapy resulted in slightly, but statistically significant, lower levels of DAS28-ESR over time (β=-0.42 (95% CI -0.67 to - 0.17)), but not RAPID3 (β=-0.58 (95% CI -0.65 to 0.49)). The effect on DAS28-ESR was entirely explained by lower swollen joint counts and was persistent after correction for confounders. CONCLUSION: These results give support to the policy that MTX should be continued in routine care patients with RA on biological therapy since this leads to better objective but not subjective clinical outcomes.
31279484 Expression and localization analyses of the cholinergic anti-inflammatory pathway and α7n 2019 Aug Rheumatoid arthritis (RA) is a complicated chronic multisystem autoimmune disease, wherein the inflammatory cascade leads to vasospasm and osteoclastogenesis, which ultimately results in bone and cartilage destruction. In this study, we investigated the expression and localization of the alpha-7 nicotinic receptor (α7nAchR) gene CHRNA7 in the heart, liver, spleen, lung, kidney, and joints of the collagen-induced arthritis (CIA) rat model. The CHRNA7 mRNA and protein expression levels in these tissues of rats from CIA and normal groups were analyzed via real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The cellular localization of CHRNA7 protein was determined via immunohistochemistry (IHC) assays. CHRNA7 was expressed at varying levels in different tissues of rats from the groups, among which joints showed significantly higher CHRNA7 expression levels than other tissues (P < 0.05). CIA rats had significantly higher CHRNA7 expression levels in the spleen and joints than the control group rats (P < 0.05). Positive expression signals for CHRNA7 were detected in various tissues of CIA and control group rats, among which strong positive signals were detected in joint fibroblast-like synoviocytes (FLSs), endothelial cells, stromal cells, and macrophages. Our results further confirmed the involvement of the CAP in the onset and development of inflammatory responses in RA, suggesting that CHRNA7 may be a new therapeutic target for RA. This study is of great clinical and theoretical significance for understanding the differential expression of CHRNA7 in various tissues and cholinergic anti-inflammatory pathway (CAP)-targeted treatment of RA.
29538755 Prevalence of sustained remission in rheumatoid arthritis: impact of criteria sets and dis 2019 Feb 1 OBJECTIVES: The aims of this national study in Sweden of patients with RA were to: examine the prevalence of sustained remission (SR), that is, remission lasting for at least 6 months; compare the prevalence of SR in patients with early RA and established RA; study the timing of onset of and time spent in SR; and study possible predictors of SR. METHODS: Adult patients with RA included in the Swedish Rheumatology Quality registry were studied. The registry was searched for patients fulfilling remission criteria: DAS28-ESR, Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and ACR/EULAR remission for at least 6 months. Early RA was defined as symptom duration ⩽6 months at inclusion in the Swedish Rheumatology Quality. RESULTS: Of 29 084 patients, 12 193 (41.9%) reached DAS28 SR at some time point during follow-up compared with 6445 (22.2%), 6199 (21.3%) and 5087 (17.5%) for CDAI, SDAI and ACR/EULAR SR, respectively. SR was more common in early RA (P < 0.001). The median time from symptom onset to SR was 1.9, 2.4, 2.4 and 2.5 years according to DAS28, CDAI, SDAI and ACR/EULAR criteria, respectively. Lower age, male sex and milder disease characteristics were associated with SR. CONCLUSION: The majority of patients in this nationwide study never reached SR. Patients with early RA are more likely to reach SR than patients with established RA.
30954464 Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppres 2019 Jun 1 Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Synovitis can cause joint injury by releasing inflammatory factors and metalloproteinases (MMPs). Therefore, it is necessary to find drugs that can control synovitis in the process of RA. Herein, we investigate the anti-inflammatory effect of Hesperidin (HSN) on fibroblast-like synovial (FLS) cells induced by lipopolysaccharide (LPS) and the protective action of M1 polarization level of synovial macrophages on antigen-induced arthritis (AIA) in order to elucidate the reduction of inflammatory cytokines and MMPs and the inhibition of macrophage activation. The functional effect of HSN on LPS-induced mRNA and protein expressions of inflammatory cytokines and MMPs in FLS cells as well as on LPS-induced macrophage M1 and M2 polarization markers was determined by quantitative real-time PCR (qPCR) or Western blot analyses, respectively. AIA in 2-month-old mice was generated using intraperitoneal injection with HSN (20 mg/kg/day) or LY294002 (20 mg/kg/day). The results show HSN significantly inhibited the LPS-induced gene expression of the inflammatory mediators. Furthermore, treatment with HSN relieved the antigen-induced arthritis and reduced the protein levels of MMP3, MMP9, and MMP13 in FLS and inhibited the polarization of macrophages to M1. Based on the results of our analyses, we concluded that HSN has significant anti-inflammatory activities and reduces the potential of MMPs in rheumatoid arthritis and the degree of polarization of macrophages to M1. Through the study of signaling pathways, we established that the inhibition of the PI3K/AKT signaling pathway by HSN may show therapeutic effects in the progression of rheumatoid arthritis.
31203399 Baseline adenosine receptor mRNA expression in blood as predictor of response to methotrex 2019 Aug Methotrexate (MTX) reduces inflammation by increasing extracellular adenosine levels in rheumatoid arthritis (RA) patients. Adenosine acts via G-protein coupled receptors; ADORA1, ADORA2a, ADORA2b and ADORA3. We studied if baseline expression of whole blood adenosine receptors can predict response to MTX. RA patients [American College of Rheumatology/European-League-Against-Rheumatism (EULAR) 2010 criteria], Disease modifying anti-rheumatic drug (DMARD) naïve with active disease [Disease Activity Score 28 (DAS28) > 3.2] were enrolled. Blood samples were collected at baseline (n = 100) and at 4 months after therapy (n = 50). Patients were treated with MTX monotherapy. Based on EULAR response, patients were categorized into three groups i.e. good, moderate and non-responders. Adenosine receptors gene expression (ADORA1, ADORA2a, ADORA2b and ADORA3) in whole-blood RNA was measured using real-time PCR. HPRT1 was used as housekeeping gene. Receptor expression at baseline was correlated with response to MTX. All values are expressed as median (interquartile range). Hundred patients [87% females; age 40 (18) years]; duration of disease 24 (24.75) months; DAS28 4.7 (1.25) were enrolled. Fifty-one were classified as good, 28 moderate and 21 as non-responders. No expression of ADORA1 and ADORA2b was detected. Significant difference was observed in the expression levels of ADORA3 between good vs non-responder (P = 0.03) and moderate vs non-responder (P = 0.002). On ROC curve analysis, ADORA3 with cut-off value of less than - 0.60 (ΔCt) predicted non-response to MTX treatment (AUC: 0.7, P = 0.006). ADORA3 mRNA levels in whole blood may serve as a biomarker of response to MTX.
31812161 Parallel comparison of fibroblast-like synoviocytes from the surgically removed hyperplast 2019 Dec 7 BACKGROUND: Fibroblast-like synoviocytes (FLS) are essential cellular components in inflammatory joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Despite the growing use of FLS isolated from OA and RA patients, a detailed functional and parallel comparison of FLS from these two types of arthritis has not been performed. METHODS: In the present study, FLS were isolated from surgically removed synovial tissues from twenty-two patients with OA and RA to evaluate their basic cellular functions. RESULTS: Pure populations of FLS were isolated by a sorting strategy based on stringent marker expression (CD45(-)CD31(-)CD146(-)CD235a(-)CD90(+)PDPN(+)). OA FLS and RA FLS at the same passage (P2-P4) exhibited uniform fibroblast morphology. OA FLS and RA FLS expressed a similar profile of cell surface antigens, including the fibroblast markers VCAM1 and ICAM1. RA FLS showed a more sensitive inflammatory status than OA FLS with regard to proliferation, migration, apoptosis, inflammatory gene expression and pro-inflammatory cytokine secretion. In addition, the responses of OA FLS and RA FLS to both the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the anti-inflammatory drug methotrexate (MTX) were also evaluated here. CONCLUSION: The parallel comparison of OA FLS and RA FLS lays a foundation in preparation for when FLS are considered a potential therapeutic anti-inflammatory target for OA and RA.
31322192 Elevated microRNA‑145‑5p increases matrix metalloproteinase‑9 by activating the nucl 2019 Sep The present study explored whether miR‑145‑5p can aggravate the development and progression of rheumatoid arthritis (RA) by regulating the expression of matrix metalloproteinases (MMPs). ELISAs, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and western blotting were used to examine the expression levels of MMP‑1, MMP‑3, MMP‑9, and MMP‑13 in fibroblast‑like synoviocytes (FLS) from patients with RA. Levels of MMP‑1, MMP‑3, MMP‑9, and MMP‑13 were assessed in the right hind ankles of a murine collagen‑induced arthritis (CIA) model by RT‑qPCR and immunohistochemical (IHC) analysis. The effects of activation or inhibition of the nuclear factor‑κB (NF‑κB) pathway on MMPs were evaluated by RT‑qPCR and western blotting. Subcellular localization of NF‑κB p65 was visualized by confocal microscopy. Overexpression of miR‑145‑5p increased the expression of MMP‑3, MMP‑9, and MMP‑13 in RA‑FLS. Moreover, injection of a miR‑145‑5p agomir into mice increased MMP‑3, MMP‑9, and MMP‑13, as demonstrated by RT‑qPCR and IHC analysis. A chemical inhibitor that selectively targets NF‑κB (BAY11‑7082) significantly attenuated MMP‑9 expression, while it did not influence the levels of MMP‑3 and MMP‑13. Immunofluorescence analysis revealed that nuclear localization of p65 was significantly enhanced, indicating that miR‑145‑5p enhances activation of the NF‑κB pathway by promoting p65 nuclear translocation. miR‑145‑5p overexpression also significantly increased phosphorylated p65 levels; however, the levels of IkB‑a were reduced in response to this miRNA. Moreover, our results indicated that miR‑145‑5p aggravated RA progression by activating the NF‑κB pathway, which enhanced secretion of MMP‑9. In conclusion, modulation of miR‑145‑5p expression is potentially useful for the treatment of RA inflammation, by regulating the expression of MMPs, and MMP‑9 in particular, through inhibition of the NF‑κB pathway.
30723868 Subclinical coronary artery disease in recent-onset of rheumatoid arthritis. 2019 Feb [No Abstract Available].
31901911 Elevated serum rheumatoid factor, anti-citrullinated protein antibodies and active rheumat 2019 Dec INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of the joints with the involvement of other systems. Previous studies have demonstrated its association with chronic periodontitis (CP), a chronic inflammatory disease of tooth-supporting tissues. Positive rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) in RA patients have been found to be associated with CP. The aim of this study is to determine the prevalence of CP in RA patients, and to investigate the association of ACPA, RF status and RA disease activity with CP and non-CP RA patients. MATERIALS AND METHODS: A comparative cross-sectional study involving 98 RA patients was conducted at Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia. Clinical oral examination was carried out to determine the CP status of RA patients. RF, ACPA and erythrocyte sedimentation rate (ESR) were measured, and the 28-joint Disease Activity Score (DAS-28) was assessed. RESULTS: Forty-five patients (45.9%) were found to have CP (95% CI: 0.36-0.56). No significant difference was observed in the prevalence of positive RF (p=0.989) or ACPA (p=0.431) in CP and non-CP RA patients. There was also no significant association between active RA disease (DAS-28 score ≥3.2) and RF positivity in CP (p=0.927) and non-CP (p=0.431) RA patients as well as ACPA positivity in CP (p=0.780) and non-CP (p=0.611) RA patients. CONCLUSION: In our cohort of RA patients, we did not find significant associations between elevated RF, ACPA, or active RA disease with the presence of CP. There were also no significant associations between elevated RF or ACPA with active RA disease.
30412238 Immunogenicity of golimumab and its clinical relevance in patients with rheumatoid arthrit 2019 Mar 1 OBJECTIVE: Golimumab immunogenicity was extensively studied during clinical development. As anti-drug antibody (ADA) detection with the standard bridging EIA (original-EIA) can yield false-negative results or underestimate ADA incidence and titres due to drug interference, a more sensitive assay was needed to determine clinical impact. METHODS: A highly sensitive drug-tolerant EIA (DT-EIA) was developed and cross-validated against the original-EIA. Samples from phase-3 subcutaneous golimumab rheumatological trials (GO-FORWARD-rheumatoid arthritis, GO-REVEAL-psoriatic arthritis, GO-RAISE-ankylosing spondylitis) were then retested. Associations between ADAs and golimumab pharmacokinetics, efficacy and safety were assessed. RESULTS: The DT-EIA was more sensitive than the original-EIA and capable of detecting ADAs amid golimumab concentrations far exceeding those in immunogenicity test samples. Consequently, an 8-fold increase in the incidence of ADAs was observed with the DT-EIA (31.7%) vs original-EIA (4.1%) in the studies. Most ADA-positive patients identified by the DT-EIA had lower antibody titres, while most with higher titres were previously identified as ADA-positive by the original-EIA. With the DT-EIA, ADA-positive patients generally had lower trough serum golimumab concentrations than ADA-negative patients; however, ADA impact on serum golimumab concentrations was more notable at higher ADA titres (⩾100). No impact of ADAs on clinical efficacy or injection-site reactions was evident. CONCLUSION: ADA incidence was expectedly higher using the DT-EIA vs original-EIA; newly detected ADAs were characterized mostly by low titres, with no impact on clinical efficacy or injection-site reactions, consistent with previously observed original-EIA results. Golimumab immunogenicity with the DT-EIA is consistent with existing knowledge regarding the clinical relevance of ADAs detected with the original-EIA in patients with rheumatological disorders. TRIAL REGISTRATION: NCT00264550, NCT00265096, NCT00265083.