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ID PMID Title PublicationDate abstract
30426454 Losartan suppresses the inflammatory response in collagen-induced arthritis by inhibiting 2019 Jun The angiotensin II type 1 receptor (AT1R) antagonist losartan has been confirmed to have a moderate anti-inflammatory effect in vitro and in vivo. However, how it affects immune cells in Rheumatoid Arthritis (RA) is still unknown. We found that in human synovial tissues, AT1R is significantly expressed on T cells and B cells. Treatment with losartan (15 mg/kg) alone and in combination with a low dose of methotrexate (MTX 0.25 mg/kg/3 days) significantly suppressed the progression of CIA. Secondary paw swelling, joint destruction and the presence of pro-inflammatory cytokines (TNF-α and IFN-γ) in the serum were alleviated after treatment. The therapeutic effects of losartan were based on reduced T-cell and B-cell activation, specifically by decreased cell vitality and pro-inflammatory cytokine production. In addition, losartan combined with a low dose of MTX achieved a similar therapeutic effect, while protecting liver and kidney from MTX damage. Mechanistically, losartan inhibits the production of pro-inflammatory mediators, reduces the phosphorylation of p38, ERK, and p65, p50 nuclear transposition in T cells and B cells. Phosphorylation of JNK is not affected by losartan in the CIA rat model. losartan can be used as an effective RA treatment, which exhibits anti-arthritic effects potentially through down-regulating the phosphorylation of p38, ERK and signaling through NF-κB. While achieving similar anti-rheumatic effects, a combination therapy of losartan with a low dose of MTX, can protect from liver and renal damage caused by giving a high dose of MTX.
30533036 Epstein-Barr virus infection and variants of Epstein-Barr nuclear antigen-1 in synovial　 2018 OBJECTIVE: The objective of the present study was to investigate Epstein-Barr virus (EBV) infection as an environmental factor for the development of rheumatoid arthritis (RA). METHODS: Synovial tissues were collected during surgery from 128 RA and 98 osteoarthritis (OA) patients. DNA was extracted from synovial tissues. The EBV gene was assessed by nested PCR for the amplification of EBV nuclear antigen-1 (EBNA-1). The nucleotide sequence of the PCR product was elucidated. HLA-DRB1 genotyping was also performed. RESULTS: EBV DNA was more frequently detected in the synovial tissues of RA patients (32.8%) than OA patients (15.3%) (p<0.01). The frequency of EBNA-1 variants did not significantly differ between RA and OA (RA: 17%, OA: 13%). The population with the HLA-DRB1 shared epitope (SE) was significantly higher in RA patients (70.3%) than in OA patients (44.9%) (p<0.001). In RA patients, the presence of EBV DNA was similar among SE-positive and -negative patients (SE-positive: 34.4%, -negative: 28.9%). The population with the EBNA-1 variant did not significantly differ between SE-positive and -negative patients (SE-positive: 12.9%, -negative: 27.3%). DISCUSSION: The present results indicate that EBV infection contributes to the onset of RA and chronic inflammation in synovial tissues. The frequency of EBNA-1 gene variants was low and not significantly different between RA and OA, suggesting that EBNA-1 gene variants are not a risk factor for RA. HLA-DRB1 with SE is a genetic risk factor for the development of RA. However, neither the presence of EBV nor EBNA-1 gene variants differed between SE-positive and -negative RA patients. Therefore, these two risk factors, SE and EBV, may be independent. CONCLUSION: EBV infection may be an environmental risk factor for the development of RA, while nucleotide variants of EBNA-1 do not appear to contribute to its development.
31331141 Role of Right Heart Catheterization in Rheumatologic Diseases - The Indian Perspective. 2018 Jun Pulmonary artery hypertension is an infrequent accompaniment of rheumatologic diseases. It could result as a complication of diseases like systemic sclerosis (SSc), systemic lupus erythomatosus (SLE), and mixed connective tissues diseases (MCTD). Very rarely, rheumatoid arthritis, dermatomyositis and Primary Sjogren's syndrome can also be complicated by a rise in pulmonary artery pressure. Pulmonary artery hypertension (PAH) can also be found in many other non rheumatologic diseases. Right heart catheterization (RHC) is the gold standard investigation in diagnosing pulmonary hypertension. This article aims to discuss the role of RHC in diagnosing pulmonary hypertension, its comparison with other modalities, the procedure, and its role in treatment of connective tissue disorders, especially with a special reference to the Indian context.
28484887 The effect of TNF-a antagonists on aortic stiffness and wave reflections: a meta-analysis. 2018 Feb Patients with rheumatoid arthritis (RA) have higher aortic stiffness and cardiovascular risk. Tumor necrosis factor alpha (TNF-a) antagonists reduce inflammation in RA and are indicated for the treatment of patients with severe active rheumatoid disease. However, it is debatable if they have favorable effects on cardiovascular health. The present meta-analysis evaluates the effect of TNF-a antagonists on aortic stiffness and wave reflections, predictors of cardiovascular events and mortality, in RA patients. A search of PubMed, Cohrane, and Embase databases was conducted to identify studies into the effect of TNF-a antagonists on aortic stiffness in RA patients. Aortic stiffness and wave reflections were assessed by aortic (carotid-femoral [cf]) pulse wave velocity (PWV) and augmentation index (AIx), respectively. cfPWV significantly improved following TNF-a antagonist treatment (mean change: -0.53 m/s, 95% CI: -0.833 to -0.218, p = 0.001), independently of age and clinical response to treatment. A more prominent reduction in cfPWV was associated with etanercept/adalimumab (mean difference: -0.62 m/s, 95% CI: -0.968 to -0.272 m/s, p < 0.001) versus infliximab (mean difference: -0.193 m/s, 95% CI: -0.847 to 0.462 m/s, p = 0.564). TNF-a antagonist treatment induced a significant improvement in AIx (mean change: -1.48%, 95% CI: -2.89 to -0.078%, p = 0.039), but this reduction was influenced by age and clinical response to treatment. The balance of evidence suggests that TNF-a antagonists may have a beneficial effect on aortic stiffness and, therefore, on cardiovascular risk. However, larger, longitudinal studies are warranted to confirm such findings.
29735168 Image analysis of fibrosis in labial salivary glands of patients with systemic autoimmune 2018 Jun Lobular fibrosis in labial salivary glands of patients with systemic autoimmune disease is a rarely examined and rather neglected histological change. Its significance and disease association is poorly understood. Our aim was to explore the clinical correlations of fibrosis in labial salivary gland samples using objective methods and laboratory parameters. Labial salivary gland samples from more than 300 patients over a 3-year period were selected from the archives of the pathology department, histologically examined, digitised, image analysed and statistically evaluated to identify the presence and intensity of lobular fibrosis, its relation to age, clinical diagnoses of systemic autoimmune disease and the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), antinuclear antibodies (ANAs), and anti-dsDNA serum markers. Significant correlation was found between lobular fibrosis and the presence of autoimmune disease (p = 0.023), mainly seropositive rheumatoid arthritis (p < 0.001). Also significant association was found between the fibrosis and the presence of serum anti-CCP (p < 0.001) and IgA/IgG/IgM-RF (p < 0.001, p < 0.001 and p = 0.008, respectively). Significant association was explored between the anti-dsDNA positivity and the negative histology groups (p = 0.033) and between the ANA positivity and the inflammation only group (p = 0.021). The results suggest that lobular fibrosis tends to associate to certain systemic autoimmune diseases, mainly seropositive rheumatoid arthritis, and seems to be rare in labial salivary gland biopsies of autoimmune diseases characterised by presence of anti-dsDNA. The close correlation of ANA positivity and the inflammation only histology was not surprising, since the majority of patients (62%) have Sjögren's syndrome, known for its inflammatory infiltrate. These findings emphasise that evaluation of lobular fibrosis and inflammation in histological samples of labial salivary gland biopsies are equally important.
29623613 Analytical variability in the determination of anti-double-stranded DNA antibodies: the st 2018 Jun Anti-dsDNA antibodies are a heterogeneous group of antibodies, quite specific for SLE. Their variability is related to the assay used, the immunoglobulin class secondary antibody, and the dsDNA source. The standardization of measuring anti-dsDNA antibodies is still poor and different methods yield different results. Several novel technologies were developed during the last decades that represent viable alternatives to the traditional methods such as the chemiluminescent immunoassay (CIA) and multiplex flow immunoassay (MFI). Additionally, positive results for anti-dsDNA antibodies can be detected in patients with inflammatory arthritis (IA) treated with different biologics reducing its clinical specificity for SLE. Anti-dsDNA antibody levels were evaluated in 246 patient samples: 70 SLE and 176 disease control (including 96 IA during treatment with different biologics), using three enzyme immunoassays (indirect enzyme immunoassay, Bio-Rad Laboratories; chemiluminescent immunoassay, Inova Diagnostics; multiplex flow immunoassay, Bio-Rad Laboratories) and three Crithidia luciliae immunofluorescence tests (CLIFT) (Euroimmun AG, Bio-Rad Laboratories, INOVA Diagnostics). Diagnostic performances were assessed both including and excluding the IA patients. Agreements, measured by the Cohen's Kappa between all methods, ranged from moderate to substantial (0.47-0.68). The clinical sensitivities for the anti-dsDNA antibody tests varied from 5.7% by CLIFT A up to 33.3% provided by EIA while the clinical specificities varied from 89.8% by MFI to 98.9% provided by CLIFT B and C. Newer technologies, such as MFI and CIA, showed great potential as a diagnostic application. Significant variations among anti-dsDNA antibody assays were observed confirming the lack of standardization.
30477052 Anaemia in Newly Diagnosed Patients of Rheumatoid Arthritis and its Correlation with Disea 2018 May AIM: To detect frequency of anemia in patients of Rheumatoid arthritis (RA) and to establish relationship between hemoglobin level and disease activity in RA. METHOD: Fifty nine patients of RA fulfilling 2010 ACR/EULAR criteria of RA having disease duration less than two years were included in the study. Haemoglobin (Hb) levels were measured. Disease activity was assessed by DAS-28 score. RESULTS: Among 40/59 (67.80%) anemic cases, 22/40 (55%) patients had anaemia of chronic disease (ACD), 11/40 (27.50%) patients had Iron deficiency anemia (IDA), 3/40 (7.5%) patients had vitamin B(12) deficiency, 1/40 (2.50%) patient had folate deficiency and 3/40 (7.50%) patients had combined IDA and vitamin B(12) deficiency. Duration of disease, rheumatoid factor positivity and occurrence of erosive disease were not significantly different among anaemic and nonanaemic patients (p>0.05 for each). Mean ESR (p>0.02) and DAS-28 (p>0.001) were statistically significantly different among anaemic and nonanaemic patients. Haemoglobin level had significant negative correlation with disease activity (DAS28) in RA cases (r -0.5533, p<0.0001). Conclusion: Anemia was seen in higher frequency in RA patients. Haemoglobin had significantly negative correlation with disease activity (DAS 28) in RA. . CONCLUSION: Anemia was seen in higher frequency in RA patients. Haemoglobin had significantly negative correlation with disease activity (DAS 28) in RA.
29237621 Patient characteristics influence the choice of biological drug in RA, and will make non-T 2018 May OBJECTIVES: With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome. METHODS: Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011-2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006-2010. RESULTS: Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably. CONCLUSIONS: There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs' safety and effectiveness.
29551357 Modified Sauvé-Kapandji procedure for the distal radioulnar joint disorders of osteoarthr 2018 May BACKGROUND: The Sauvé-Kapandji (SK) procedure is one of several surgical options in the treatment of distal radioulnar disorders by osteoarthritis (OA) and rheumatoid arthritis (RA). While satisfactory postoperative clinical results were obtained in most cases, instability of the proximal ulnar stump and radioulnar convergence are the most common complications. Minami et al. have developed a modification of the SK procedure that maintains the transverse diameter of the distal radioulnar joint and stabilizes the proximal ulnar stump, using a half-slip of the extensor carpi ulnaris tendon. In this study, the modified SK procedure was performed on 83 patients with distal radioulnar disorders, due to OA and RA. MATERIALS AND METHODS: We evaluated the clinical and radiographical postoperative results with an average follow-up period of 82.3 months. RESULTS: Post-operative extension of the wrist and pronation/supination of the forearm had significantly improved with the exception of wrist flexion. Postoperative x-rays showed no instability of the proximal ulnar stump in both coronal and lateral planes. However, breakage of the drilled hole at the proximal ulnar stump occurred in 10 cases, and of these, there was instability of the proximal ulnar stump in 5 cases. CONCLUSIONS: This modification is very simple and does not require extension of the surgical field. This paper concludes that the modified SK procedure is a safe and effective surgical intervention of distal radioulnar disorders from OA and RA.
29486148 Glycomics meets artificial intelligence - Potential of glycan analysis for identification 2018 Jun In this study, one hundred serum samples from healthy people and patients with rheumatoid arthritis (RA) were analyzed. Standard immunoassays for detection of 10 different RA markers and analysis of glycan markers on antibodies in 10 different assay formats with several lectins were applied for each serum sample. A dataset containing 2000 data points was data mined using artificial neural networks (ANN). We identified key RA markers, which can discriminate between healthy people and seropositive RA patients (serum containing autoantibodies) with accuracy of 83.3%. Combination of RA markers with glycan analysis provided much better discrimination accuracy of 92.5%. Immunoassays completely failed to identify seronegative RA patients (serum not containing autoantibodies), while glycan analysis correctly identified 43.8% of these patients. Further, we revealed other critical parameters for successful glycan analysis such as type of a sample, format of analysis and orientation of captured antibodies for glycan analysis.
30376894 Potential therapeutic antibodies targeting specific adiponectin isoforms in rheumatoid art 2018 Oct 30 BACKGROUND: Different adiponectin isoforms appear to be differentially involved in the pathogenesis of various diseases. The purpose of this study was to generate monoclonal antibodies (mAbs) specific to different adiponectin isoforms and investigate whether these mAbs have potential as therapeutic agents for such diseases. METHODS: Hybridoma cells producing monoclonal antibodies were generated and screened using enzyme-linked immunosorbent assay and Western blotting for the production of mAbs recognizing human adiponectin isoforms. RESULTS: The mAb from hybridoma clone KH7-41 recognized both the middle molecular weight (MMW) (hexamer) and low molecular weight (LMW) (trimer) isoforms of adiponectin in human serum, whereas the KH7-33 mAb detected only MMW (hexamer) adiponectin. The KH4-8 clone recognized both the high molecular weight (HMW) (multimer) and MMW adiponectin isoforms. However, in mouse and rat sera, the abovementioned antibodies recognized only the MMW isomer. These mAbs also recognized adiponectin in various human tissues, such as lung, kidney, and adipose tissues, although the three mAbs had different staining intensities. The mAb from clone KH4-8 effectively inhibited increases in interleukin-6 (IL-6) and IL-8 expression in recombinant adiponectin-stimulated human osteoblasts and human umbilical vein endothelial cells. Also, the mAbs KH7-33 and KH4-8 significantly ameliorated rheumatic symptoms in a collagen-induced arthritis mouse model. This result suggests that these mAb treatments may ameliorate adiponectin-mediated inflammatory response. CONCLUSIONS: mAbs against human adiponectin isomers can potentially be developed as therapeutic antibodies to target specific detrimental isoforms of adiponectin while maintaining the functions of beneficial isoforms.
30235245 Evaluation of surfactant proteins A, B, C, and D in articular cartilage, synovial membrane 2018 OBJECTIVE: Surfactant Proteins (SPs) are well known from lung and form, along with phospholipids, a surface-active-layer at the liquid-air-interface of the alveolar lining. They play a major protective role by lowering surface tension, activating innate and adaptive immune defense at the lung mucosal interface, especially during infection. We analyzed the regulation of SPs in human and mouse articular chondrocytes, synoviocytes, and synovial fluid under healthy and inflammatory conditions, as well as in tissues of patients suffering from osteoarthritis and rheumatoid arthritis. METHODS: Immunohistochemistry, RT-PCR, qRT-PCR, ELISA, Western blotting were performed in cell cultures and tissue samples to determine localization, regulation, and concentration of SPs. RESULTS: All four SPs, were expressed by healthy human and mouse articular chondrocytes and synoviocytes and were also present in synovial fluid. Treatment with inflammatory mediators like IL-1β and TNF-α led to short-term upregulation of individual SPs in vitro. In tissues from patients with osteoarthritis and rheumatoid arthritis, protein levels of all four SPs increased significantly compared to the controls used. CONCLUSION: These results show the distribution and amount of SPs in tissues of articular joints. They are produced by chondrocytes and synoviocytes and occur in measurable amounts in synovial fluid. All four SPs seem to be differently regulated under pathologic conditions. Their physiological functions in lowering surface tension and immune defense need further elucidation and make them potential candidates for therapeutic intervention.
30180453 [Expression of dishevelled-2 in cartilage of rheumatoid arthritis and its effect on cartil 2018 Sep 1 Objective: To study the expression of dishevelled-2 (DVL2) in rheumatoid arthritis cartilage and its effect on cartilage destruction. Methods: Cartilage DVL2 expression in rat models of rheumatoid arthritis (RA), osteoarthritis(OA) and collagen-induced arthritis(CIA) were tested by Western blotting. DVL2 overexpressed lentivirus was transfected into the knee of CIA rats. Primary chondrocytes were extracted from RA patients by knee arthroplasty and transfected with DVL2 overexpressed lentivirus. Gene expression of related inflammation related cytokines was detected by real-time polymerase chain reaction (PCR) . Results: Compared with knee articular cartilage in OA patients and normal rats, DVL2 protein was highly expressed in knee cartilage of RA patients and CIA rats (P values 0.041 and 0.032, respectively). DVL2 did not significantly affect the destruction of knee cartilage in CIA rats (P=0.885). DVL2 overexpression in chondrocytes enhanced gene expression of cyclo-oxygenase-2 (COX-2), inducible nitric oxide synthase (NOS), matrix metalloproteinase (MMP) 2, MMP-3, and MMP-9, which could be more pronounced when tumor necrosis factor alpha was added. Conclusions: DVL2 is highly expressed in RA articular cartilage and promotes the expression of inflammatory cytokines and MMP gene in chondrocytes by activating Wnt/β-catenin pathway, which involves in the destruction of articular cartilage in RA.
29857511 Sphingolipidomic Profiling of Rat Serum by UPLC-Q-TOF-MS: Application to Rheumatoid Arthri 2018 May 31 Sphingolipids (SPLs) are biologically important molecules, but the structural diversity and complexity of SPLs brings significant analytical challenges for their study. In this paper, we have developed an UPLC-Q-TOF-MS-based sphingolipidomic approach for the comprehensive identification and quantification of SPLs in rat serum. A total of 120 SPLs covering seven subcategories were identified for the first time. Method validations including linearity, sensitivity, reproducibility, and recovery were also evaluated. This method was exemplarily applied to characterize the SPL alterations in rheumatoid arthritis (RA) rats and the intervention effects of indomethacin (IDM). Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the IDM-treated group exhibited a trend to recover the controls. Twenty-six significantly changed SPL markers were explored, and the levels of ceramides (Cers) and their metabolites were found to be reversed by IDM treatment. These results indicate that IDM exerts anti-arthritic effects through the suppression of Cer-mediated COX-2 activation and resulting PEGâ‚‚ liberation. The present study demonstrates a promising potential of this method for the understanding of RA and the anti-arthritic mechanisms of relevant drugs.
29449499 Clinical Correlates, Outcomes, and Predictors of Inflammatory Ocular Disease Associated wi 2018 May OBJECTIVE: Inflammatory ocular disease (IOD) is a rare but severe extraarticular manifestation of rheumatoid arthritis (ExRA) with high mortality. The aim of our study was to examine clinical characteristics of IOD in rheumatoid arthritis (RA) and their effect on disease severity and outcomes in recent years. METHODS: A retrospective cohort of RA patients with IOD evaluated between 1996 and 2013 was assembled and compared to RA comparators without IOD and matched for age, sex, and disease duration. RESULTS: We identified 92 patients (69% female; mean age 62 yrs) with IOD: 33 scleritis, 23 episcleritis, 21 peripheral ulcerative keratitis (PUK), 14 uveitis, and 1 with orbital inflammation. The majority of patients with scleritis, episcleritis, and PUK was seropositive versus uveitis (> 80% vs 62%, p = 0.048). PUK and scleritis were more symptomatic compared to episcleritis and uveitis, and often required systemic therapy. Time to resolution was longer in scleritis than episcleritis (p = 0.01). PUK, scleritis, and uveitis had severe ocular sequelae. Prevalence of severe ExRA (18% vs 4%, p = 0.004) and dry eye syndrome (42% vs 26%, p = 0.024) was higher among patients with IOD than comparators. The incidence of new ExRA over 5-year followup was also higher among cases (29% vs 11%, p = 0.022). Ten-year survival was similar among RA patients with and without IOD (66% vs 64%, p = 0.56), with no differences noted among IOD subtypes. CONCLUSION: This large single-center study highlights the variable presentation and outcomes of IOD in RA. Although ocular complications are associated with significant morbidity, it is reassuring that survival among those with IOD is now similar to those without ocular disease.
28898565 Projected Burden of Osteoarthritis and Rheumatoid Arthritis in Australia: A Population-Lev 2018 Jun OBJECTIVE: To forecast the prevalence and direct health care costs of osteoarthritis (OA) and rheumatoid arthritis (RA) in Australia to the year 2030. METHODS: An epidemiologic model of the Australian population was developed. Data on the national prevalence of OA and RA were obtained from the Australian Bureau of Statistics (ABS) 2014-2015 National Health Survey. Future prevalence was estimated using ABS population projections for 2020, 2025, and 2030. Available government data on direct health care expenditure for OA and RA were modeled to forecast costs (in Australian $) for the years 2020, 2025, and 2030, from the perspective of the Australian public health care system. RESULTS: The number of people with OA is expected to increase nationally from almost 2.2 million in 2015 to almost 3.1 million Australians in 2030. The number of people with RA is projected to increase from 422,309 in 2015 to 579,915 in 2030. Health care costs for OA were estimated to be over $2.1 billion in 2015; by the year 2030, these are forecast to exceed $2.9 billion ($970 for every person with the condition). Health care costs for RA were estimated to be over $550 million in 2015, including $273 million spent on biologic disease-modifying antirheumatic drugs. Health care costs for RA are projected to rise to over $755 million by the year 2030. CONCLUSION: OA and RA are costly conditions that will impose an increasing health care burden at the population level. These projections provide tangible data that can be used to map future health service provision to expected need.
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.
29884867 A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis. 2018 Jun 8 It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.
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.
30641538 Determinants of non-nociceptive pain in Rheumatoid Arthritis. 2018 Oct INTRODUCTION: Features suggestive of neuropathic pain (NP) have been described in RA in addition to nociceptive pain. We aimed to determine the clinical predictors of NP in RA patients and study its association with radiographic structural damage. METHODS: Cross-sectional study was performed with RA patients followed at our Rheumatology department. Patients with diagnosed neuropathy of other origin, non-RA related risk factors for NP (e.g. diabetes mellitus) or fibromyalgia according to expert opinion were excluded. Demographic and clinical data were collected and disease activity/functional measures were evaluated. Two questionnaires were applied to assess NP: the Leeds Assessment of Neuropathic Symptoms (LANSS) and the painDETECT questionnaire (PDQ). Radiographs performed in up to 12 months before/after the evaluation were classified according to the modified van der Heijde Sharp´s method. Univariate and multivariate logistic regression were performed to identify the predictors of NP. RESULTS: 112 patients were included. 86 (77%) were women, with a mean (SD) age of 55.1 (10.8) years and median disease duration of 13 [2-41] years. 45 (40%) patients had NP by the LANSS (≥12) and 28% had a possible/likely NP in the PDQ (≥13). Female sex was predictive of NP by both tests and disease duration was inversely associated with LANSS NP. After adjusting for those two variables, pain VAS and TJC were positive predictors of NP by both tests. The same was not true for SJC, ESR or CRP levels. DAS28-CRP was significantly associated with PDQ NP, losing its statistical significance after adjustment for TJC and pain VAS. The HAQ score increased the odds of NP for both tests, independently of DAS 28-CRP. Positivity for ACPA and previous/current hydroxychloroquine treatment had lower odds of NP. 90 patients performed radiographic evaluation. Joint narrowing score was a significant negative predictor of LANSS NP. After adjusting for global radiographic score, current methotrexate treatment had lower odds of LANSS NP and previous/current leflunomide was a positive predictor of NP by both tests. CONCLUSION: NP was associated with disease activity/functional scores but not with objective inflammatory measures. Greater structural damage, increased disease duration and ACPA positivity did not seem to increase the odds of NP. Possible association of NP and underlying csDMARD treatment was uncovered.