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ID PMID Title PublicationDate abstract
28239846 Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated sy 2017 May BACKGROUND AND PURPOSE: Abnormal glycolytic metabolism contributes to joint inflammation in rheumatoid arthritis (RA). The aims of this study were to investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a bifunctional enzyme that controls the glycolytic rate, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and invasiveness in RA. EXPERIMENTAL APPROACH: A specific inhibitor of PFKFB3, PFK15, and siRNA were used to evaluate the role of PFKFB3. Protein expression was measured by Western blotting or immunofluorescence staining. The expression of cytokines was determined by quantitative real-time PCR. Migration and invasion were measured using a Boyden chamber assay. A mouse model of collagen-induced arthritis (CIA) was used to evaluate the in vivo effect of PFK15. KEY RESULTS: PFKFB3 expression was increased in the synovial tissue and FLSs from RA patients compared with osteoarthritis patients. PFKFB3 inhibition decreased the expression of IL-8, IL-6, CCL-2 and CXCL-10 and the proliferation, migration and invasion of RA FLSs. PFK15 suppressed TNF-α-induced activation of NF-κB and p38, JNK and ERK MAPK signals in RA FLSs. PFK15 treatment also suppressed glucose uptake and lactate secretion. Lactate reversed the inhibitory effect of PFK15 or PFKFB3 siRNA on cytokine expression and migration of RA FLSs. Lactate was also involved in PFKFB3-mediated activation of NF-κB and MAPKs. Intraperitoneal injection of PFK15 in mice with CIA attenuated joint inflammation. CONCLUSION AND IMPLICATIONS: Elevated PFKFB3 expression might contribute to synovial inflammation and aggressive behaviours of RA FLSs, suggesting a novel strategy of targeting PFKFB3 to prevent synovial inflammation and joint destruction in RA.
28569211 Exosomal amyloid A and lymphatic vessel endothelial hyaluronic acid receptor-1 proteins ar 2017 May 31 BACKGROUND: Exosomes are thought to play an important role in exchanging information between cells. The proteins and lipids in exosomes play roles in mediating inflammatory and autoimmune diseases. The aim of this study was to identify exosomal candidate proteins that are related to other inflammatory parameters in rheumatoid arthritis (RA). METHODS: The study population consisted of 60 patients with RA: 30 in the clinical remission (CR) group with a Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) ≤2.6 and 30 in the non-clinical remission (non-CR) group with a DAS28-ESR >2.6. Preparation of exosomes from patient serum samples was performed with the ExoQuick kit, and protein identification/quantification was performed using tandem mass tag labeling/mass spectrometry and an enzyme-linked immunosorbent assay. Comparisons between groups were made using Student's t test or the Mann-Whitney U test, as appropriate. Spearman's correlation coefficients (ρ) were calculated. RESULTS: We identified six candidate proteins. Exosomal levels of amyloid A (AA) and lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) differed between the CR and non-CR groups. Both serum and exosomal AA levels were higher in the non-CR group than in the CR group (p = 0.001). Significant positive correlations were found between exosomal AA and C-reactive protein (CRP) as well as between serum AA and CRP (ρ = 0.614, p = 0.001, and ρ = 0.624, p = 0.001, respectively). Although serum levels of LYVE-1 did not differ between the non-CR and CR groups, exosomal levels of LYVE-1 were lower in the non-CR group than in the CR group (p = 0.01). We identified positive correlations between serum/exosomal LYVE-1 and CRP only in the non-CR group (serum ρ = 0.376, p = 0.04; exosome ρ = 0.545, p = 0.002). CONCLUSIONS: Exosomal LYVE-1 shows potential for use as an additional marker of disease activity in patients with RA, and exosomes may carry other useful markers for RA.
27797749 Differential impact of obesity on the pathogenesis of RA or preclinical models is continge 2017 Apr OBJECTIVE: Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models. METHODS: Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis. RESULTS: We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency. CONCLUSIONS: We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms.
29238019 [Inflammation and osteoclasts]. 2017   Osteoclasts are differentiated from precursors of the monocyte/macrophage lineage originated from bone marrow hematopoietic stem cells and are the sole bone-resorbing cells in the body. Osteoclast differentiation is thought to require M-CSF (macrophage colony-stimulating factor) and RANKL (receptor activator of nuclear factor kappa-B ligand) signaling. However, it has recently been proposed that under chronic inflammatory conditions, such as systemic autoimmune diseases (e.g., rheumatoid arthritis), an increase in inflammatory cytokine levels within joints induces pathological osteoclast differentiation, causing excessive bone resorption. In addition, the authors have reported that stimulating mouse bone marrow monocytes and human CD14(+) monocytes with combination of TNFα and IL-6 can induce differentiation of osteoclast-like cells, which are cells with bone resorption activity. In the present article, we discuss the mechanism of osteoclast differentiation of RANKL-independent bone-resorbing cells, using both data from the aforementioned report as well as the latest findings. Understanding the mechanisms underlying RANKL-independent, cytokine-mediated osteoclast differentiation could facilitate the development of novel therapies for inflammatory joint diseases.
29187339 Sophocarpine suppress inflammatory response in human fibroblast-like synoviocytes and in 2017 Sep 1 Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting nearly 1% of adults worldwide. This study aimed to investigate whether sophocarpine is a potential drug for treating RA. The cytotoxicity of sophocarpine to RA-fibroblast-like synoviocytes (FLSs) was evaluated using 3-[4,-dimethylthiazol-2-y]-2,5-diphenyl-tetrazolium bromide (MTT) assays kit and released lactate dehydrogenase (LDH) assays. The transcription of proinflammatory cytokines in RA-FLSs was analyzed by reverse transcription and real-time polymerase chain reaction (RT-PCR). The proteins levels were further verified by enzyme-linked immunosorbent assay (ELISA). The alterations in the mediators of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways were tested by western blotting. The clinical effects of sophocarpine were evaluated in type II collagen-induced arthritis (CIA) in DBA-/1 mouse model by scoring their clinical responses, synovitis, and cartilage destructions, and ELISA was employed to analyze the concentrations of proinflammatory cytokines in the serum of CIA mice. The results showed that sophocarpine contained low cytotoxicity to RA-FLS cells, and it was capable to downregulate the expressions of LPS-induced proinflammatory cytokines. The suppressions of MAPK and NF-κB signaling pathways by sophocarpine were also found in LPS-induced RA-FLSs. The attenuation of the symptoms in CIA mouse model were significant, in which concentrations of proinflammatory cytokines were decreased after the sophocarpine treatment. In this study, we demonstrated the potential of sophocarpine in treating RA, both in vitro and in vivo. Sophocarpine may be a potential drug in treating human RA.
28539551 [Suppression of GPI-induced arthritis by oral administration of transgenic rice seeds expr 2017 OBJECTIVE: To investigate the effects and mechanisms of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI(325-339)) in mice model of GPI induced arthritis (GIA). METHODS: We generated transgenic rice expressing APL12 which was analog peptide of hGPI(325-339). The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined IL-17 production from splenocytes and inguinal lymph node (iLN) and mesenteric lymph nodes (mLN) cells and analyzed the expression levels of functional molecules from splenocytes and iLN cells. RESULTS: Prophylactic treatment of GIA mice with APL12 transgenic rice seeds (APL12-TG) significantly improved the severity of arthritis, histopathological arthritis scores, and decreased titers of serum anti-GPI antibodies, BAFF mRNA in iLN cells, IL-17 production in splenocytes and iLN cells compared with non-transgenic rice-treated mice. APL12-TG-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4(+)CD25(+) cells in the spleen. CONCLUSION: APL12-TG improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on regulatory T cells in spleen.
28771535 Association between periodontitis and the risk of palindromic rheumatism: A nationwide, po 2017 OBJECTIVE: To estimate the association between a history of periodontitis (PD) and the risk of incident palindromic rheumatism (PR). METHODS: Using a nationwide, administrative database, this study identified 4,421 newly-diagnosed PR cases from 2007 to 2012 and randomly selected 44,210 non-PR controls matched (1:10) for sex, age and the year of the index date. After adjusting for comorbid diabetes mellitus, we estimated the odds ratios (ORs) with 95% confidence intervals (CIs) using conditional logistic regression analysis to quantify the association between a history of PD and the risk of PR. The influences of the lag time and severity of PD were examined by calculating ORs for subgroups of patients based on the time interval between the last PD-related visit and the index date and PD-related cumulative cost and number of visit. RESULTS: This study showed an association between a history of PD and incident PR (OR, 1.51; 95% CI, 1.41-1.61). The association remained significant after variation of PD definitions. The magnitude of the association was greater in those with shorter lag time between the latest date of PD diagnosis and PR index date and those who had a higher number of visits for PD or a greater cumulative cost for PD-related visits. After excluding 569 PR patients who developed rheumatoid arthritis after the index date, we found a consistent time- and dose-dependent association between PD and PR risk. CONCLUSION: This study demonstrated a time- and dose-dependent association between PD exposure and PR risk.
28102737 Platelet microvesicles in health and disease. 2017 May Interest in cell-derived extracellular vesicles and their physiological and pathological implications is constantly growing. Microvesicles, also known as microparticles, are small extracellular vesicles released by cells in response to activation or apoptosis. Among the different microvesicles present in the blood of healthy individuals, platelet-derived microvesicles (PMVs) are the most abundant. Their characterization has revealed a heterogeneous cargo that includes a set of adhesion molecules. Similarly to platelets, PMVs are also involved in thrombosis through support of the coagulation cascade. The levels of circulatory PMVs are altered during several disease manifestations such as coagulation disorders, rheumatoid arthritis, systemic lupus erythematosus, cancers, cardiovascular diseases, and infections, pointing to their potential contribution to disease and their development as a biomarker. This review highlights recent findings in the field of PMV research and addresses their contribution to both healthy and diseased states.
28840350 Regulatory T cells and IL-10 as modulators of chikungunya disease outcome: a preliminary s 2017 Dec Regulatory T (Treg) cells hold centre stage in regulating the immune responses in most viral infections. However, their involvement in chikungunya infection is unexplored. In the current study, the frequencies and functionality of peripheral Treg and T effector (Teff) cells were assessed during different phases of chikungunya by flow cytometry and in-vitro cytokine assays. Treg cells were also studied in rheumatoid arthritis (RA) patients, whose symptoms closely mimic chronic chikungunya arthritis patients. Frequency of Treg cells was lower in acute and chronic chikungunya arthritis patients than in recovered individuals and controls, and comparable among recovered individuals and controls. Treg/Teff ratio was lower in acute than in chronic chikungunya arthritis patients, recovered individuals and controls. Higher secretion of CHIKV specific IL-10 was observed in recovered individuals than in acute, chronic chikungunya arthritis patients and controls. Frequencies of Treg and Teff cells were higher and Treg/Teff ratio was lower in RA patients than in chronic chikungunya arthritis patients. The results indicate that reduction of Treg cells was associated with ongoing CHIKV infection and normalization of Treg cells with resolution of disease. Contrasting phenotypic data in RA and chronic chikungunya arthritis suggest an altogether different mechanism of Treg-mediated pathology in both arthritis conditions. Overall, our preliminary study, suggesting an association of peripheral Treg cells and IL-10 with recovery from chikungunya, may provide insight into chikungunya disease prognosis and warrants further study.
28255642 Dose relationship between oral glucocorticoids and tumor necrosis factor inhibitors and th 2017 Jul The objective of this study was to evaluate the impact of oral glucocorticoid (GC) dose on rates of hospitalized infectious events (HIEs) among RA patients newly exposed to tumor necrosis factor inhibitor (TNFi) therapy. This retrospective cohort study used data from the MarketScan claims database. Incident and prevalent adult RA patients newly exposed to TNFi therapy were identified and assigned to three cohorts: no GC, low-dose GC (≤7.5 mg), and high-dose GC (>7.5 mg); patients could contribute exposure time to multiple cohorts if they changed dose or discontinued GC. The primary outcome was estimated incidence rate (IR) of HIEs per 100 patient-years of GC exposure. A total of 40,933 eligible patients were identified (mean age 53.0 years; 77.4% female). HIE risk increased with increasing GC dose: the IR [95% confidence interval (CI)] was 3.9 (3.63-4.13) for no GC; 6.4 (5.68-7.16) for low-dose GC; and 13.3 (11.9-15.5) for high-dose GC. Adjusted rate ratios (95% CI) were 1.4 (1.21-1.60) for low-dose vs no GC; 2.8 (2.32-3.34) for high-dose vs no GC, and 2.0 (1.66-2.45) for high-dose vs low-dose GC. The risk of HIEs increased with increasing age. HIE risk did not increase with longer exposure to GCs. Oral GCs, regardless of dose, significantly increased the risk of HIEs among RA patients newly initiating TNFi therapy. Steroid dosing must be considered when assessing infection risk in treatment decisions for RA patients.
28363826 Precision and sources of variability in the assessment of rheumatoid arthritis erosions by 2018 Mar OBJECTIVES: To assess the precision and the sources of variation due to repositioning of the manual measurement of erosions located on the metacarpophalangeal joints (MCP) with High-Resolution peripheral Quantitative Computed Tomography (HRpQCT) in rheumatoid arthritis (RA). METHODS: RA patients with at least one erosion on the 2nd, 3rd or 4th MCP on conventional radiographs were included. Two scans were performed the same day with repositioning. The main outcome was to calculate the short-term precision of the width, depth, and volume of erosions. Secondary outcomes were intra-operator and inter-operator precision, the least significant change, and the sources of variability of the measurement. RESULTS: Twenty-nine patients were included, allowing analysis of 406 erosions from 0.9 to 3mm of diameter. Intraclass correlation coefficients (ICC) for the precision of the measurement of the axial width, axial depth, and volume after repositioning were 0.80, 0.96, and 0.99, respectively. RMS CV and RMS SD were 16%, 0.26mm; 17.5%, 0.32mm; and 19.7%, 0.93mm(3), respectively. For intra-operator precision, ICCs were 0.92, 0.97, and 0.99 with RMS CV of 16%, 16.4%, and 18.7%, respectively. Inter-operator precision of the volume was 0.99 with RMS CV of 14%. Least significant change of width, depth, and volume were 0.3mm, 0.2mm, and 0.3mm(3). There was no significant correlation with bone microarchitecture parameters. CONCLUSION: HRpQCT analysis is a reproducible method to characterize and measure erosions, without effect of the repositioning. However, we showed weak precision in manual measurement due to intra-operator variability.
29080437 Nursing sensitive outcomes in patients with rheumatoid arthritis: A systematic literature 2018 Jan BACKGROUND: Although rheumatology nursing has been shown to be effective in managing patients with rheumatoid arthritis, patient outcomes sensitive to nursing interventions (nursing sensitive outcomes) have not been systematically studied. OBJECTIVES: The objective of this study was to identify and delineate relevant patient outcomes measured in studies that reported nursing interventions in patients with rheumatoid arthritis. DESIGN: A systematic search was conducted from 1990 to 2016. Inclusion criteria were (i) patients with rheumatoid arthritis, (ii) adult population age ≥16years, (iii) nurse as part of the care team or intervention delivery, (iv) primary research only, (v) English language, and (vi) quantitative studies with nursing sensitive outcomes. DATA SOURCES: Medline, CINAHL, Ovid nursing, Cochrane library and PsycINFO databases were searched for relevant studies. REVIEW METHODS: Using the predetermined inclusion/exclusion criteria, nine reviewers working in pairs assessed the eligibility of the identified studies based on titles and abstracts. Papers meeting the inclusion criteria were retrieved and full texts were further assessed. Critical Appraisal Skills Programme tools were used to assess the quality of the included studies. Data on nursing sensitive outcomes were extracted independently by two reviewers. The Outcome Measures in Rheumatology comprehensive conceptual framework for health was used to contextualise and present findings. RESULTS: Of the 820 articles retrieved, 7 randomised controlled trials and 3 observational studies met the inclusion criteria. Seventeen nursing sensitive outcomes were identified (disease activity, clinical effects, pain, early morning stiffness duration, fatigue, patient safety issues, function, knowledge, patient satisfaction, confidence in care received, mental health status, self-efficacy, patient attitude/perception of ability to control arthritis, quality of life, health utility, health care resources, death). These fitted into 10 health intervention domains in keeping with the pre-specified conceptual framework for health: disease status, effectiveness, safety, function, knowledge, satisfaction, psychological status, quality of life, cost, death. A total of 59 measurement instruments were identified comprising patient reported outcome measures (n=31), and biologic measures and reports (n=28). CONCLUSIONS: This review is notable in that it is the first to have identified, and reported, a set of multidimensional outcome measures that are sensitive to nursing interventions in rheumatology specifically. Further research is required to determine a core set of outcomes to be used in all rheumatology nursing intervention studies.
28560470 Cost per response for abatacept versus adalimumab in rheumatoid arthritis by ACPA subgroup 2017 Jul Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.
29243056 Association between urinary sodium and potassium excretion and blood pressure and inflamma 2018 Apr Hypertension is highly prevalent in patients with rheumatoid arthritis (RA). In other populations, high sodium (Na(+)) and low potassium (K(+)) intake are associated with an increased risk of hypertension, and in animal models, a high salt intake exacerbated arthritis. Patients with RA have many comorbidities associated with salt sensitivity, but their salt intake and its relationship to blood pressure and inflammation is unknown. Using the Kawasaki formula, Na(+) and K(+) urinary excretion (reflecting intake) was estimated in 166 patients with RA and 92 controls, frequency matched for age, sex, and race. Inflammatory markers and disease activity were measured in RA patients. We tested the associations between blood pressure and Na(+) and K(+) excretion. Estimated 24-h Na(+) excretion was similarly high in both RA (median [IQR] 5.1 g, [3.9-6.6 g]) and controls (4.9 g, [4.0-6.5 g]), p = 0.9, despite higher rates of hypertension in RA (54 vs. 39%, p = 0.03). The Na(+):K(+) excretion ratio was significantly higher in RA (2.0 [1.6-2.4]) vs. 1.7 [1.5-2.1]), p = 0.02] compared to controls. In RA, a lower K(+) excretion was inversely correlated with diastolic blood pressure (adjusted β = - 1.79, p = 0.04). There was no significant association between Na(+) or K(+) excretion and inflammatory markers. Despite a similar Na(+) excretion, patients with RA had higher rates of hypertension than controls, a finding compatible with increased salt sensitivity. Patients with RA had a lower Na(+):K(+) excretion ratio than controls, and lower K(+) excretion was associated with higher diastolic blood pressure in RA.
28129626 MiR-650 inhibits proliferation, migration and invasion of rheumatoid arthritis synovial fi 2017 Apr BACKGROUND AND OBJECTIVES: This study was aimed to investigate the effects of miR-650 on the proliferation, migration, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue samples were collected from 16 rheumatoid arthritis (RA) patients and 13 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-650 and AKT2 expressions in both synovial tissues and cells were detected using the quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC). Dual luciferase reporter gene assay was employed to evaluate the effect of miR-650 on the luciferase activity of AKT2. Then RASFs were transfected with miR-650 mimics, miR-650 inhibitors and pLenti6/V5-AKT2 respectively. And changes in cellular proliferation, migration, invasion and apoptosis were detected through MTT assay, wound healing assay, Transwell invasion assay and flow cytometry analysis, respectively. RESULTS: MiR-650 was significantly down-regulated in RASFs than normal cells, whereas AKT2 was up-regulated in RASFs. Dual luciferase reporter gene assay showed that miR-650 could specifically bind to the 3'UTR of AKT2 and significantly repress the luciferase activity. MiR-650 significantly decreased the expression of AKT2. Down-regulation of miR-650 or up-regulation of AKT2 could increase proliferation, migration, invasion of RASFs, and decrease RASFs apoptosis. The conversed results were observed, when miR-650 was up-regulated in RASFs. CONCLUSIONS: MiR-650 could inhibit the proliferation, migration and invasion of RASFs through targeted regulation of AKT2 expression.
28215593 Influence of MTHFR C677T gene polymorphism in the development of cardiovascular disease in 2017 Apr 30 OBJECTIVE: To investigate the association between increased carotid intima-media thickness (CIMT), homocysteine level, and MTHFR C677T (rs1801133) gene polymorphism in Egyptian people with rheumatoid arthritis (RA). SUBJECTS AND METHODS: 280 Egyptian women (160 RA patients and 120 controls) were included in the study. CIMT was measured using high resolution B-mode ultrasonography and homocysteine levels were measured using enzyme-linked immunosorbent assay. While, MTHFR C677T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We found that subjects who carried the TT genotype and T allele were significantly more likely to develop RA with 2.9 and 1.5 fold, respectively. RA patients carrying the T allele presented a statistically significant increased risk of developing atherosclerosis compared with those carrying the C allele. Moreover, MTHFR TT genotype was independent risk factor of thick CIMT. CONCLUSIONS: C677T MTHFR gene polymorphism is associated with RA in Egyptians. MTHFR 677TT carriers had higher concentrations of serum Hcy than did subjects harboring the CC and CT genotypes. The presence of 677T allele increases the risk of atherosclerosis in patients with RA. This increased risk of atherosclerosis could be due to hyperhomocysteinemia.
28460018 Evaluation of the diagnostic accuracy of hand and foot MRI for early Rheumatoid Arthritis. 2017 Aug 1 OBJECTIVES: To assess the diagnostic value of MRI for early RA. In some RA patients, a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence for its reliability is limited. METHODS: MRI of hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic (229 presented with RA, 159 with other arthritides and 201 with UA). Symptom-free controls provided a reference for defining an abnormal MRI. In preliminary investigations, MRI of patients who presented with RA was compared with MRI of symptom-free controls and of patients with other arthritides. Thereafter, the value of MRI in early RA diagnosis was determined in UA patients using the 1-year follow-up on fulfilling the 1987 RA criteria and start of disease-modifying drugs as outcomes. RESULTS: Preliminary investigations were promising. Of the UA patients, 14% developed RA and 37% started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA development independent of other types of MRI-detected inflammation [odds ratio (OR) = 7.5, 95% CI: 2.4, 23] and also independent of age and other inflammatory measures (swollen joints, CRP) (OR = 4.2, 95% CI: 1.4, 12.9). Within UA patients, the negative predictive value of abnormal tenosynovitis was 95% (95% CI: 89%, 98%) and the positive predictive value 25% (95% CI: 17%, 35%). The performance was best in the subgroup of UA patients presenting with oligoarthritis (18% developed RA): the positive predictive value was 36% (95% CI: 23%, 52%), the negative predictive value was 98% (95% CI: 88%, 100%), the sensitivity was 93% (95% CI: 70%, 99%) and the specificity was 63% (95% CI: 51%, 74%). CONCLUSION: MRI contributes to the identification of UA patients who will develop RA, mostly in UA patients presenting with oligoarthritis.
28664285 [Psoriasis vs. psoriatic arthritis : Similarities and differences in the pathophysiology]. 2017 Aug Psoriasis is a chronic inflammatory skin disease with genetic and (auto)immunological backgrounds. Up to 30% of patients with psoriasis also develop a mostly oligoarticular arthritis with spinal involvement that is termed psoriatic arthritis (PsA) and shows a specific joint pattern which differs from that of rheumatoid arthritis (RA). Both Psa and psoriasis share a common main axis, the interleukin (IL) 23/IL17 pathway as well as major overlaps in the functions of tumor necrosis factor alpha (TNFalpha). Recently acquired knowledge supports the concept that in both diseases, similar genetic dispositions and molecular pathways lead to organ-specific disease patterns. In some types of PsA, genetic predisposition and the relevance of acute inflammatory reactions appear to be greater that in psoriasis, while in the latter exogenous factors and T‑lymphocyte reactions in the skin seem to have a higher impact. A key difference between PsA and cutaneous psoriasis is the largely irreversible nature of inflammatory joint changes in PsA, whereas cutaneous plaques in psoriasis completely heal. The question of how interdependent both diseases are and whether immunologically primed T‑lymphocytes from cutaneous lesions in PsA may transmit the disease to the synovial membranes and induce acute inflammation is not precisely known. A detailed analysis of these organ-specific differences may not only provide an explanation for the similar, but partly different efficacy of novel therapeutic strategies but may also lead to the development of personalized therapies that take into account the individually different manifestations of the diseases over time.
27837198 Comparison of ultrasonographic joint and tendon findings in hands between early, treatment 2017 Jun Although both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) may lead to joint deformity, SLE arthritis is typically non-erosive and often accompanied by Jaccoud's deformity. Therefore, we examined characteristics of joint and tendon lesions in patients with SLE and RA by ultrasonography. Fifteen treatment-naïve SLE patients and 40 treatment-naïve RA patients with joint symptoms were included in this study. The hand joints and related tendons were ultrasonographically examined using grey-scale (GS) and power Doppler (PD). Joint involvement was comparably observed in patients with SLE and RA (80% versus 95%, p = 0.119). However, tendon involvement was more frequent in SLE than in RA (93% versus 65%, p = 0.045), especially in the wrist joints (73% versus 40%, p = 0.037). When we investigated the intensity of US findings, the joint synovitis score (GS + PD) per affected joint was lower in SLE than RA (2.0 versus 2.6, p = 0.019), while tendon inflammation score was not significantly different (2.1 versus 2.2, p = 0.738). Finally, the examination of concordance between joint and tendon involvement in the same finger revealed that joint lesion appeared in only 49% of fingers having tendon involvement in the SLE group, which was significantly less than 74% in the RA group ( p = 0.010). Thus, as compared with RA, SLE arthropathy is characterized by the predominance of tenosynovitis/periextensor tendon inflammation, which is likely to develop independently from joint synovitis.
29221596 Role of the lung in individuals at risk of rheumatoid arthritis. 2017 Feb Antibody-positive (seropositive) rheumatoid arthritis (RA) is a complex multiphasic disease developing in genetically susceptible individuals following environmental challenges (such as smoking). RA-associated autoantibodies can develop several years before any clinical signs of joint inflammation, suggesting that triggering of this autoimmunity occurs outside the joints. Epidemiological, clinical, and molecular studies in seropositive individuals at risk for developing RA as well as in early untreated RA suggest a potential role for mucosal sites (especially lung mucosa) as RA-associated autoimmunity trigger sites. This chapter summarizes clinical and molecular studies supporting the lung as a central site for autoimmunity initiation in RA.