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31076943 Comorbidity burden and clinical characteristics of patients with difficult-to-control rheu 2019 Sep INTRODUCTION: Difficult-to-treat rheumatoid arthritis (RA) is a significant clinical problem despite no clear definition. We aimed to provide clinical characteristics and associated comorbidities of RA patients in relation to disease control. METHODS: RA characteristics and physician-recorded comorbidities were analyzed in a sample of 1937 RA patients. Patients treated for RA for 5.2 y (IQR, 2.1-11.3) were classified as difficult-to-control when presenting with DAS28-ESR > 3.2 despite previous use of at least 2 csDMARDs. A comparison of demographic and RA-related characteristics between difficult-to-treat and low disease activity patients (DAS28-ESR ≤ 3.2) was performed. Comorbidity burden was assessed by calculating Rheumatic Diseases Comorbidity Index (RDCI). Logistic regression model was constructed for difficult-to-control disease. RESULTS: Hypertension (46.9% (95%CI, 44.7-49.2)), coronary artery disease (CAD) (18.5% (95%CI, 16.8-20.3)), and diabetes (14.4% (95%CI, 12.9-16.0)) were the most prevalent conditions in RA patients. When compared with the adequate control group, difficult-to-control patients were increasingly burdened with hypertension (52.7% (95%CI, 47.5-57.8) vs. 42.0% (95%CI, 36.6-47.6); p = 0.006), cardiovascular diseases (24.2% (95%CI, 20.1-28.9) vs. 11.1% (95%CI, 8.0-15.1); p < 0.001), respiratory system diseases (7.0% (95%CI, 4.8-10.2) vs. 3.3% (95%CI, 1.8-5.9); p = 0.03) and gastroduodenal ulcers (2.3% (95%CI, 1.2-4.4) vs. 0.3% (95%CI, 0.1-1.8); p = 0.04). Patients with higher RDCI had lower chance to obtain low disease activity (OR 0.69 (95%CI, 0.61-0.79); p < 0.001). In multivariate analysis, RDCI was independently associated with difficult-to-control disease (OR 1.46 (95%CI, 1.21-1.76); p < 0.001). CONCLUSIONS: RA patients suffer from a variety of comorbidities. Cardiovascular and respiratory system diseases occur twice as often in difficult-to-control patients. RDCI may provide a valuable tool in evaluating a risk for difficult-to-control RA. Key Points • Hypertension, coronary artery disease and diabetes are the most prevalent comorbidities in rheumatoid arthritis. • Cardiovascular and respiratory tract diseases as well as gastroduodenal ulcers are more common among difficult-to-control patients, when compared with subjects with adequately controlled RA. • Rheumatic Diseases Comorbidity Index is an independent predictor for difficult-to-control RA.
30260019 Identification of differentially expressed genes in synovial tissue of rheumatoid arthriti 2019 Mar Rheumatoid arthritis (RA) and osteoarthritis (OA) are the common joints disorder in the world. Although they have showed the analogous clinical manifestation and overlapping cellular and molecular foundation, the pathogenesis of RA and OA were different. The pathophysiologic mechanisms of arthritis in RA and OA have not been investigated thoroughly. Thus, the aim of study is to identify the potential crucial genes and pathways associated with RA and OA and further analyze the molecular mechanisms implicated in genesis. First, we compared gene expression profiles in synovial tissue between RA and OA from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Gene Expression Series (GSE) 1919, GSE55235, and GSE36700 were downloaded from the GEO database, including 20 patients of OA and 21 patients of RA. Differentially expressed genes (DEGs) including "CXCL13," "CD247," "CCL5," "GZMB," "IGKC," "IL7R," "UBD///GABBR1," "ADAMDEC1," "BTC," "AIM2," "SHANK2," "CCL18," "LAMP3," "CR1," and "IL32." Second, Gene Ontology analyses revealed that DEGs were significantly enriched in integral component of extracellular space, extracellular region, and plasma membrane in the molecular function group. Signaling pathway analyses indicated that DEGs had common pathways in chemokine signaling pathway, cytokine-cytokine receptor interaction, and cytosolic DNA-sensing pathway. Third, DEGs showed the complex DEGs protein-protein interaction network with the Coexpression of 83.22%, Shared protein domains of 8.40%, Colocalization of 4.76%, Predicted of 2.87%, and Genetic interactions of 0.75%. In conclusion, the novel DEGs and pathways between RA and OA identified in this study may provide new insight into the underlying molecular mechanisms of RA.
29781829 Comparison of Adults With Polyarticular Juvenile Idiopathic Arthritis to Adults With Rheum 2019 Jun BACKGROUND/OBJECTIVE: Many individuals with juvenile idiopathic arthritis (JIA) have persistent disease into adulthood. Polyarticular JIA (pJIA) is often mislabeled as rheumatoid arthritis (RA) in adult rheumatology clinics, and treatment for adult pJIA patients is not well defined. We aimed to describe clinical features and medication use in the adult pJIA population in relation to an RA control cohort. METHODS: We performed a cross-sectional study of 45 adults with pJIA and 94 with RA seen from 2013 to 2017. Clinical characteristics including RA classification criteria were compared using χ and McNemar tests. Medication use was analyzed focusing on tumor necrosis factor inhibitor (TNFi) survival, and an accelerated failure-time model was developed for time to methotrexate initiation. RESULTS: Polyarticular JIA patients were less likely to be rheumatoid factor or cyclic citrullinated peptide antibody positive; fewer than half of pJIA subjects met the RA 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria. Time from diagnosis to methotrexate initiation was associated with longer disease duration in both groups (p < 0.01). Current TNFi use was more prevalent in pJIA patients (49% vs. 18%, p < 0.01), and TNFi use, particularly for etanercept, was sustained longer with a median drug survival of 4.41 years compared with 0.70 years in RA patients (p < 0.01). CONCLUSIONS: Although often considered together in adult rheumatology practice, adults with pJIA are distinct from patients with RA. Medication use markedly differed between the 2 populations with greater prevalence and duration of TNFi use in pJIA patients. Further study is needed to improve outcomes in this unique population.
30321952 The Salto total ankle arthroplasty - Clinical and radiological outcomes at five years. 2019 Aug BACKGROUND: Modern designs of total ankle arthroplasty (TAA) have the potential to treat symptomatic ankle OA without adversely affecting ankle biomechanics. We present the mid-term results of a modern, mobile-bearing TAA design. METHODS: TAA was performed in 50 consecutive patients (55 ankles) in an independent, prospective, single-centre series. Implant survival, patient-reported outcome measures (PROMs) and radiographic outcomes are presented at a mean of five years (range 2-10.5years). RESULTS: A total of three patients (four ankles) died and two (two ankles) were lost to follow-up. Three TAAs were revised for aseptic loosening (in two cases) or infection. Two further patients underwent reoperations, one for arthroscopic debridement of anterolateral synovitis and one for grafting of an asymptomatic tibial cyst. With all-cause revision as an endpoint, implant survival was 93.3% at five to ten years (95% CI 80.5%-97.8%). If reoperations are included this falls to 90.2% (95% CI 75.6%-96.3%) at five years. No other patient demonstrated radiographic evidence of loosening or subsidence. PROMs and satisfaction were excellent at latest follow-up. CONCLUSION: At five years, the outcomes for this design of TAA in this series were excellent, and were similar to those of previously published series from the designer centre.
30835702 Perioperative outcomes associated with thoracolumbar 3-column osteotomies for adult spinal 2019 Jun 1 OBJECTIVE: Spinal deformity causing spinal imbalance is directly correlated to pain and disability. Prior studies suggest adult spinal deformity (ASD) patients with rheumatoid arthritis (RA) have more complex deformities and are at higher risk for complications. In this study the authors compared outcomes of ASD patients with RA following thoracolumbar 3-column osteotomies to outcomes of a matched control cohort. METHODS: All patients with RA who underwent 3-column osteotomy for thoracolumbar deformity correction performed by the senior author from 2006 to 2016 were identified retrospectively. A cohort of patients without RA who underwent 3-column osteotomies for deformity correction was matched based on multiple clinical factors. Data regarding demographics and surgical approach, along with endpoints including perioperative outcomes, reoperations, and incidence of proximal junctional kyphosis (PJK) were reviewed. Univariate analyses were used to compare patients with RA to matched controls. RESULTS: Eighteen ASD patients with RA were identified, and a matched cohort of 217 patients was generated. With regard to patients with RA, 11.1% were male and the mean age was 68.1 years. Vertebral column resection (VCR) was performed in 22.2% and pedicle subtraction osteotomy (PSO) in 77.8% of patients. Mean case length was 324.4 minutes and estimated blood loss (EBL) was 2053.6 ml. Complications were observed in 38.9% of patients with RA and 29.0% of patients without RA (p = 0.380), with a trend toward increased medical complications (38.9% vs 21.2%, p = 0.084). Patients with RA had a significantly higher incidence of deep vein thrombosis (DVT)/pulmonary embolism (PE) (11.1% vs 1.8%, p = 0.017) and wound infections (16.7% vs 5.1%, p = 0.046). PJK occurred in 16.7% of patients with RA, and 33.3% of RA patients underwent reoperation. Incidence rates of PJK and reoperation in matched controls were 12.9% and 25.3%, respectively (p = 0.373, p = 0.458). At follow-up, mean sagittal vertical axis (SVA) was 6.1 cm in patients with RA and 4.5 cm in matched controls (p = 0.206). CONCLUSIONS: Findings from this study suggest that RA patients experience a higher incidence of medical complications, specifically DVT/PE. Preoperative lower-extremity ultrasounds, inferior vena cava (IVC) filter placement, and/or early initiation of DVT prophylaxis in RA patients may be indicated. Perioperative complications, morbidity, and long-term outcomes are otherwise similar to non-RA patients. ABBREVIATIONS: AKI = acute kidney injury; ASA = American Society of Anesthesiologists; ASD = adult spinal deformity; CSVL = central sacral vertical line; DMARDs = disease-modifying antirheumatic drugs; DVT = deep vein thrombosis; EBL = estimated blood loss; HRQOL = health-related quality of life; IVC = inferior vena cava; LOS = length of stay; LL = lumbar lordosis; ODI = Oswestry Disability Index; PE = pulmonary embolism; PI = pelvic incidence; PI-LL = PI − LL mismatch; PJK = proximal junctional kyphosis; PT = pelvic tilt; PSO = pedicle subtraction osteotomy; RA = rheumatoid arthritis; SVA = sagittal vertical axis; TK = thoracic kyphosis; UIV = upper instrumented vertebra; UTI = urinary tract infection; VAS = visual analog scale; VCR = vertebral column resection; VTE = venous thromboembolism.
30357805 Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis. 2019 Aug Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated, resulting in poor delivery of oxygen; this, along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, and thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state. This alters redox-sensitive signalling pathways and also results in the accumulation of metabolic intermediates which, in turn, can act as signalling molecules that further exacerbate the inflammatory response. The RA synovium is a multi-cellular tissue, and while many cell types interact to promote the inflammatory response, their metabolic requirements differ. Thus, understanding the complex interplay between hypoxia-induced signalling pathways, metabolic pathways and the inflammatory response will provide better insight into the underlying mechanisms of disease pathogenesis.
31454755 IL-17, IL-21 and IL-22 polymorphisms in rheumatoid arthritis: A systematic review and meta 2020 Jan BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune systemic disease and in its pathogenesis participate several proinflammatory cytokines, including those produced by Th17 cells. We performed a systematic review aiming to assess the associations between polymorphisms in Th17 cytokines, namely IL-17A, IL-17F, IL-21 and IL-22, and susceptibility to RA. METHODS: We searched three electronic databases (MEDLINE, Scopus and Web of Science) for observational studies assessing the association between susceptibility to RA (or its clinical presentation) and polymorphisms of the cytokines IL-17A, IL-17F, IL-21 and IL-22. From the selected studies, we extracted information on the studied polymorphisms, assessed outcomes, and demographic characteristics of participants. We performed random effects meta-analyses assessing the associations between susceptibility to RA and different genotypes of the IL-17A rs2275913, IL-17Frs763780 andIL-17Frs2397084polymorphisms. Primary studies' quality was assessed using the Q-Genie tool. RESULTS: Fifteen studies were included in this systematic review. Five IL-17A polymorphisms were reported to be associated with susceptibility to RA. For the IL-17A rs2275913 polymorphism, our meta-analysis showed the AA genotype to be significantly associated with lower susceptibility to RA(OR = 0.76; 95%CI = 0.61-0.93;p = 0.01), while the opposite was observed for the GG genotype (OR = 1.20; 95%CI = 1.06-1.35;p = 0.01). Concerning IL-17Frs763780 polymorphism, theTT genotype was found to be significantly less frequent in RA patients(OR = 0.49; 95%CI = 0.31-0.77;p = 0.002), while the opposite was observed for the CT genotype (OR = 2.00; 95%CI = 1.03-3.87;p = 0.04). No significant associations were found regarding rs2397084polymorphisms. For IL-21, rs6822844 and rs4505848 were described to have significant associations with susceptibility to RA. No studies were found assessing IL-22 polymorphisms in RA. CONCLUSIONS: IL-17A rs2275913 and IL-17F rs763780 polymorphisms are significantly associated with susceptibility to RA and with different clinical characteristics of this disease.
31171525 Swollen, but not tender joints, are independently associated with ultrasound synovitis: re 2019 Sep OBJECTIVES: Joint swelling and tenderness are considered a proxy for inflammation in patients with rheumatoid arthritis (RA). With ultrasound-detected inflammation as reference, our objectives were to explore on patient and joint level the associations between ultrasound synovitis and joint swelling, tenderness and patient-reported joint pain (PRJP). METHODS: 209 patients with established RA were examined six times during 12 months with assessment of 32 joints in upper/lower extremities for joint swelling/tenderness and Grey scale (GS)/power Doppler (PD) synovitis. PRJP was assessed on a manikin. Correlations between different sum scores were at each examination calculated using Spearman's rho (r), agreement at joint level was examined by Cohen's kappa and logistic regression models were used to explore the associations between joint assessment and GS/PD scores. RESULTS: At patient level, swollen joints were strongly correlated with GS/PD sum scores (r=0.64-0.88), while tender joints were primarily associated with PRJP (r=0.54-0.68). At joint level, GS/PD pathology had higher agreement with swelling (kappa 0.54-0.57) than tenderness (kappa 0.20-0.21) or PRJP (0.23-0.25). Higher percentages of joints were swollen according to increasing GS/PD scores, independently of joint tenderness. However, joints being tender, but not swollen, were not associated with GS/PD scores. Receiver operating curves showed swollen but not tender joints to be associated with GS/PD scores. CONCLUSIONS: Swollen joints were strongly associated with ultrasound detected synovitis at both patient and joint level, while this association was not found for tender joints. These results may question if tender joints reflect ongoing inflammation in established RA.
30446358 "Am I OK?" using human centered design to empower rheumatoid arthritis patients through pa 2019 Mar OBJECTIVE: Use of patient reported outcomes (PROs) in the routine care of rheumatoid arthritis (RA) has been shown to improve health outcomes, However, integration of PROs into the clinical visit is inconsistent. We aimed to develop a "dashboard" for RA patients to display relevant PRO measures for discussion during a routine RA clinical visit. METHODS: Patients (N = 45) and providers (N = 12) were recruited from rheumatology clinics at a university center and a safety net hospital. Using a human-centered design process involving patients, clinicians, designers, and health-IT experts, we performed interviews, clinic observations, and focus groups, which subsequently guided an iterative phase of prototype testing. RESULTS: RA patients and their providers shared the goals of assessing wellbeing and developing a personalized treatment plan. We found conflicting views of which data were most important for guiding decision-making and for answering the patient's overarching question of "Am I OK?" CONCLUSION: The final dashboard simplified the display of PRO data and correlated it longitudinally to the patient's medication regimen. It also included laboratory values relevant for RA care. PRACTICE IMPLICATIONS: By presenting data graphically, the dashboard may provide a platform for patients and providers to communicate around PROs and shared goals.
31186464 General synovitis score and immunologic synovitis score reflect clinical disease activity 2019 Jun 11 The purpose of this study was to investigate the relationship between clinical disease activity in patients with advanced stage rheumatoid arthritis (RA) on treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and histopathological scores of synovial inflammation. To this end, synovial biopsies of 62 RA patients who underwent surgery for either synovectomy or total joint arthroplasty were assessed by a general synovitis score (GSS) and an immunologic synovitis score (IMSYC). The clinical disease activity index (CDAI) was significantly correlated with both the GSS and the IMSYC (r = 0.65, p = <0.001, r = 0.68, p = <0.001). Compared to patients with moderate and high disease activity, there was a significantly lower expression of T cell (CD3), B cell (CD20) and neutrophil (CD15) markers in synovial tissue of patients with low activity, but similar expression of the macrophage marker CD68. Subgroup analyses revealed no differences between small and large joints, seropositive and seronegative RA and patients with or without prednisolone treatment. However, we found a significantly stronger correlation of CDAI with IMSYC in patients undergoing arthroplasty (r = 0.82) than in patients undergoing synovectomy (r = 0.55). In addition, there was a stronger correlation of CDAI with GSS in patients treated with methotrexate (r = 0.86) than in patients with TNFα blockade (r = 0.55). In summary, the present study demonstrates that the histopathological scores GSS and IMSYC in general reflect clinical disease activity in patients with advanced stage rheumatoid arthritis, but that there is some heterogeneity between subgroups of patients within the cohort. In the future, molecular characterization of synovial inflammatory cell populations, including plasma cell infiltrates, will help to further defined clinically important subtypes of RA and treatment response.
30861615 A Prospective Study of the Development of Inflammatory Arthritis in the Family Members of 2019 Sep OBJECTIVE: To determine the incidence of inflammatory arthritis and autoantibody prevalence in Indigenous North American people. METHODS: Unaffected relatives of Indigenous North Americans with rheumatoid arthritis (RA) from central Canada and Alaska were systematically monitored from 2005 to 2017. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) were tested at every visit, and a subset was tested for ACPA fine specificity using a custom multiplex assay. Multistate models based on all available study visits were developed to determine the likelihood of transitioning between autoantibody states, or to inflammatory arthritis. RESULTS: Eighteen of 374 relatives (4.8%) developed inflammatory arthritis during follow-up (after a mean ± SD of 4.7 ± 2.4 years), yielding a transition rate of 9.2 cases/1,000 person-years. Thirty percent of those who developed inflammatory arthritis were seronegative at baseline, but all were seropositive at inflammatory arthritis onset. Although 30% of ACPA/RF double-seropositive individuals developed inflammatory arthritis (after 3.2 ± 2.2 years), the majority of these individuals did not develop inflammatory arthritis. Multistate modeling indicated a 71% and 68% likelihood of ACPA and RF seropositive states, respectively, reverting to a seronegative state after 5 years, and a 39% likelihood of an ACPA/RF double-seropositive state becoming seronegative. Fine specificity testing demonstrated an expansion of the ACPA repertoire prior to the development of inflammatory arthritis. CONCLUSION: Despite a high incidence of inflammatory arthritis in this cohort of at-risk relatives of Indigenous North Americans with RA, a large proportion of autoantibody-positive individuals do not develop inflammatory arthritis and revert back to an autoantibody-negative state.
30851708 Taraxasterol suppresses inflammation in IL-1β-induced rheumatoid arthritis fibroblast-lik 2019 May Previous study has indicated that taraxasterol (TAR), one of bioactive pentacyclic triterpenes mainly isolated from Chinese medicine herb Taraxacum officinale, displays considerable anti-inflammatory effects in various kinds of models. However, its effects on rheumatoid arthritis (RA) have still not been elucidated. In this study, we aim to investigate its anti-inflammatory effects and underlying mechanisms of TAR against RA using both interleukin (IL)-1β-stimulated human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) in vitro and collagen-induced arthritis (CIA) mice in vivo. Firstly, our results demonstrated that TRA significantly suppressed the IL-1β-induced expressions of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-6, and IL-8 and productions of matrix metalloproteinases (MMPs), like MMP-1 and MMP-3 in HFLS-RA in vitro. Moreover, TRA alleviated arthritis progressions and prevented inflammatory processes in the joint tissues of CIA mice in vivo. Further mechanism studies indicated that TRA blocked nuclear factor kappa B (NF-κB) activation via modulating inhibitor of kappa B (IκB), IκB kinase (IKK) and transforming growth factor-β-activated kinase 1 (TAK1). Results also demonstrated that TRA suppressed the NOD-like receptor protein 3 (NLRP3) inflammasomes through blocking expressions of NLRP3, apoptosis-associated speck-like protein containing (ASC), and caspase-1 in both IL-1β-induced HFLS-RA and CIA mice. In conclusions, current findings suggested that TRA might one of considerable therapeutic compounds for relieving rheumatoid arthritis progress via suppressing inflammations through modulating NF-κB and NLRP3 inflammasomes pathways.
30868182 Opportunistic screening for osteoporosis using thoraco-abdomino-pelvic CT-scan assessing t 2019 Jun INTRODUCTION: Screening for osteoporosis is crucial in rheumatoid arthritis (RA) patients. The aim of this study was to assess the value of thoraco-abdomino-pelvic CT-derived bone mineral density (BMD) results in L1, compared to dual energy X-ray absorptiometry (DXA) results for osteoporosis screening in rheumatoid arthritis patients. METHODS: Consecutive RA patients who underwent a CT-scan and DXA within a 2-year period were retrospectively included. The CT sagittal images were then evaluated for vertebral fractures from T4 to L5 using the Genant classification. The CT-attenuation values (in Hounsfield units (HU)) of trabecular bone in L1 were measured on axial images and compared to the DXA results. RESULTS: This study included 105 patients (mean age 61.1 years (± 9.5), 78.1% women). There were 28 patients (26.7%) with DXA-defined osteoporosis and 32 (30%) with osteoporotic fractures (vertebral and/or non-vertebral). The CT assessment indicated that the mean (SD) vertebral L1 attenuation was 142.2 HU (± 18.5). The diagnostic performance for the vertebral CT-attenuation measurement was acceptable: the AUC was 0.67 for predicting osteoporotic fractures and of 0.69 for predicting vertebral fractures. Among patients with osteoporotic fractures, there were 23 (74%) patients categorized as osteoporotic with a L1 CT-attenuation of 135 HU or less, whereas there were only 13 patients (42%) identified by DXA. CONCLUSION: CT offers a combined opportunistic screening for osteoporosis by assessing both vertebral fractures and bone density on routine CT-scans. This approach may be particularly interesting for RA patients with a high osteoporosis risk.
31814483 Spinal sagittal balance associated with age, vertebral fracture, and functional disability 2020 Nov Objectives: The purpose of this study was to assess the relationships between spinal sagittal balance and functional ability of Japanese patients with rheumatoid arthritis.Methods: A total of 491 patients with rheumatoid arthritis who underwent the measurement of sagittal vertical axis for the assessment of spinal sagittal balance were enrolled. Factors associated with sagittal vertical axis were analyzed by categorizing patients according to sagittal vertical axis (<4 cm, 4-9.5 cm, and >9.5 cm). In addition, univariate and multivariate regression analysis were performed to identify factors associated with Health Assessment Questionnaire Disability Index (HAQ-DI) in different age groups.Results: The percentage of patients with sagittal vertical axis <4 cm, 4-9.5 cm, and >9.5 cm was 61.1%, 32.4%, and 6.5%, respectively. Age, vertebral fracture, and gait speed were associated with sagittal vertical axis. Sagittal vertical axis was associated with HAQ-DI in the 80-90 years age group.Conclusion: Sagittal balance was associated with age, vertebral fracture, and gait speed. In super-aged patients with rheumatoid arthritis, HAQ-DI was affected by sagittal balance. Management of super-aged patients with rheumatoid arthritis should include evaluation of joints as well as spinal alignment.
31389580 MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway. 2019 Aug OBJECTIVE: To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway. MATERIALS AND METHODS: A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting. RESULTS: The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p<0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p<0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p<0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p<0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p<0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p<0.05), while they were higher in model group than those in control group (p<0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p<0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p<0.05). CONCLUSIONS: MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal.
31858337 Meta-analysis: diagnostic accuracy of the citrullinated peptides derived from fibrinogen a 2020 Apr OBJECTIVES: Anticitrullinated protein/peptide antibodies (ACPAs) have shown valuable effects in the diagnosis of rheumatoid arthritis (RA). Both fibrinogen and vimentin are significant antigens of ACPAs. This study evaluated the diagnostic performance of fibrinogen and vimentin peptides in RA. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies published in English until January 2019 that evaluated the utility of the peptides of both vimentin and fibrinogen. The bivariate mixed-effects model and summary receiver operating characteristic (SROC) curve were used to estimate sensitivity and specificity across studies. RESULTS: Seven peptides from 19 studies were included. The pooled sensitivities of Fibα36-50, Fibα563-583, Fibα580-600, Fibα621-635, Fibβ36-52, Fibβ60-74, and Vim60-75 were 35%, 41%, 18%, 26%, 0.53%, 57%, and 44%, respectively. The pooled specificities of Fibα36-50, Fibα563-583, Fibα580-600, Fibα621-635, Fibβ36-52, Fibβ60-74, and Vim60-75 were 97%, 98%, 98%, 98%, 97%, 98%, and 98%, respectively. The SROC areas under the curve (AUCs) of Fibα36-50, Fibα563-583, Fibα580-600, Fibα621-635, Fibβ36-52, Fibβ60-74, and Vim60-75 were 0.92, 0.85, 0.64, 0.82, 0.91, 0.96, and 0.86, respectively. CONCLUSION: Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA. The diagnostic accuracies of Fibβ60-74 and Fibβ36-52 were better than those of Vim60-75, Fibα36-50, and Fibα563-583, and all of them were better than that of Fibα621-635 and Fibα580-600.Key Points• Our study summarized the diagnostic accuracy of peptides derived from fibrinogen and vimentin and evaluated the diagnostic value of different peptides for RA patients.• Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA.
31681279 Characterization of Phenotypes and Functional Activities of Leukocytes From Rheumatoid Art 2019 Background: Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease and leads to persistent chronic inflammation. The pathophysiology of the disease is complex, involving both adaptive and innate immunity. Among innate immune cells, neutrophils have been rarely studied due to their sensitivity to freezing and they are not being collected after Ficoll purification. Methods: We used mass cytometry to perform a multidimensional phenotypic characterization of immune cells from RA-treated patients, which included the simultaneous study of 33 intra- or extra-cellular markers expressed by leukocytes. We were able to focus our study on innate immune cells, especially neutrophils, due to a specific fixation method before freezing. In addition, blood samples were stimulated or not with various TLR agonists to evaluate whether RA-dependent chronic inflammation can lead to immune-cell exhaustion. Results: We show that RA induces the presence of CD11b(low) neutrophils (33.7 and 9.2% of neutrophils in RA and controls, respectively) associated with the duration of disease. This subpopulation additionally exhibited heterogeneous expression of CD16. We also characterized a CD11a(high) Granzyme B(high) T-cell subpopulation possibly associated with disease activity. There was no difference in cytokine expression after the stimulation of immune cells by TLR agonists between RA and controls. Conclusion: Mass cytometry and our fixation method allowed us to identify two potential new blood subpopulations of neutrophils and T-cells, which could be involved in RA pathology. The phenotypes of these two potential new subpopulations need to be confirmed using other experimental approaches, and the exact role of these subpopulations is yet to be studied.
30724436 Tuned Cationic Dendronized Polymer: Molecular Scavenger for Rheumatoid Arthritis Treatment 2019 Mar 22 Cell-free deoxyribonucleic acid (cfDNA) released from either dead or damaged cells serves as a key autoantigen in rheumatoid arthritis (RA). They can be recognized by nucleic acid (NA) sensors such as the toll-like receptor (TLR), leading to activation of the innate immune system and chronic inflammation. Developed here is a cationic molecular scavenger, by screening cationic dendronized polymers, which eliminates cfDNA and inhibits TLR recognition and nucleic-acid-induced inflammation. The structure-property study demonstrates that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect by exquisite control of the molecular structure. In addition, the optimized cationic polymer effectively inhibited joint swelling, synovial hyperplasia, and bone destruction in collagen-induced arthritis (CIA) rat models. The results offer support for synthetic polymers offering new paradigm in autoimmune disease treatment.
31398424 Efficacy and safety of Ramucirumab and methotrexate co-therapy in rheumatoid arthritis exp 2019 Oct 1 Rheumatoid arthritis (RA) is a chronic and progressive autoimmune inflammatory disease associated with irreversible joint destruction that leads to permanent motor disability and compromised quality of life. However, the main cause of RA is still unknown though stimulation of immune system and cells plays pivotal role in disease development and progression. Ramucirumab (RAM) is the monoclonal antibody against VEGF- receptor. This study aimed to investigate and evaluate the therapeutic effect of RAM with or without Methotrexate (MTX) against adjuvant-induced arthritis in rats. Complete Freund's adjuvant (CFA)-induced arthritic rats were treated for three consecutive weeks with MTX or RAM alone and MTX-RAM co-therapy. Arthritic score, gait score, ankle diameter, paw thickness, angiogenic, inflammatory cytokines, bone erosion markers, and apoptotic markers were assessed to evaluate the anti-arthritic effect. RAM monotherapy exhibited anti-inflammatory, anti-angiogenic and anti-apoptotic effects similar to MTX alone to treat RA in the current study. Furthermore, RAM alone had a protective effect on bone and cartilage health better than standard anti-rheumatic agent MTX. Interestingly, combined therapy of MTX and RAM produced significant differences in comparison with MTX or RAM monotherapy in all tested parameters. Moreover, the current study proved that MTX-RAM co-therapy has a synergistic effect.
31332995 Association of Tumor Necrosis Like factor 1 A (TL1A) and its Decoy Receptor (DcR3) with Th 2019 Jan Different cytokines play roles in the pathogenesis and tissue damage of Rheumatoid Arthritis (RA) including, Tumor necrosis factor superfamily (TNFSF) and their receptors particularly TNF-like ligand 1A (TL1A), and its decoy receptor DcR3. This study included 150 subjects, of them 50 patients having Rheumatoid Arthritis (RA), 50 patients with Osteoarthritis (OA), and 50 normal controls. Clinical examination was done and data was collected from patient's sheets, routine laboratory investigations included, rheumatoid factor (RF) antibody, anti-cyclic citrullinated peptide (anti-CCP) antibody, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Disease activity score 28 was calculated and used to measure the activity of RA. Serum and synovial fluid (SF) TL1A and DcR3 levels were measured by (ELISA), while IL-17 was measured in supernatant fluid of PBMC culture after stimulation with recombinant human (rh) TL1A. Results showed significantly higher levels of TL1A and its decoy receptor DcR3 in RA patients than the other two groups. It was also found that TL1A is significantly related to the disease activity and enhances IL-17 production after stimulation of PBMC. These results can guide scientists to the future substitutions in the way of treatment of various inflammatory and autoimmune diseases.