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ID PMID Title PublicationDate abstract
30338640 Impact of subclinical synovitis in ankles and feet detected by ultrasonography in patients 2019 Jan OBJECTIVE: To investigate the impact of subclinical synovitis detected by ultrasonography (US) on the ankles and feet of patients with rheumatoid arthritis. METHODS: We retrospectively reviewed the data of patients (n = 59) who underwent US. RESULTS: The functional ability and quality of life (QoL) of patients in the subclinical group were impaired. While the physician visual analog scale (VAS) scores significantly decreased in the subclinical group, patient and pain VAS scores significantly decreased only in patients without synovitis. CONCLUSION: US-detected subclinical foot and ankle synovitis considerably affected patient functional status and QoL; however, it was often unnoticed by physicians.
30173149 Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Asso 2018 Nov OBJECTIVE: To investigate predictors of flare in rheumatoid arthritis (RA) patients with low disease activity (LDA) and to evaluate the effect of flare on 12-month clinical outcomes. METHODS: Patients with RA who were taking disease-modifying antirheumatic drugs and had a stable 28-joint count Disease Activity Score (DAS28) < 3.2 were eligible for inclusion. At baseline and every 3 months, clinical (DAS28), functional [Health Assessment Questionnaire-Disability Index (HAQ-DI), EQ-5D, Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F), Medical Outcomes Study Short Form-36 (SF-36)], serum biomarkers [multibiomarker disease activity (MBDA) score, calprotectin, CXCL10], and imaging data were collected. Flare was defined as an increase in DAS28 compared with baseline of > 1.2, or > 0.6 if concurrent DAS28 ≥ 3.2. Cox regression analyses were used to identify baseline predictors of flare. Biomarkers were cross-sectionally correlated at time of flare. Linear regressions were performed to compare clinical outcomes after 1 year. RESULTS: Of 152 patients, 46 (30%) experienced a flare. Functional disability at baseline was associated with flare: HAQ-DI had an unadjusted HR 1.82 (95% CI 1.20-2.72) and EQ-5D had HR 0.20 (95% CI 0.07-0.57). In multivariate analyses, only HAQ-DI remained a significant independent predictor of flare (HR 1.76, 95% CI 1.05-2.93). At time of flare, DAS28 and its components significantly correlated with MBDA and calprotectin, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers. Patients who flared had significantly worse outcomes at 12 months (HAQ-DI, EQ-5D, FACIT-F, SF-36, and radiographic progression). CONCLUSION: Flares occur frequently in RA patients with LDA and are associated with worse disease activity, quality of life, and radiographic progression. Higher baseline HAQ-DI was modestly predictive of flare, while biomarker correlation at the time of flare suggests a noninflammatory component in a majority of events.
29368271 Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivit 2018 Feb INTRODUCTION: To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA). METHODS: Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR-BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2-immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1-3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored. RESULTS: A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [-], 102 anti-CCP2+ [34 iter group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2- group. DXR-BMD was lower in the anti-CCP2+ vs. the anti-CCP2- groups (Gp1-3 vs. anti-CCP2-: P < 0.0001 for left and right hands). DXR-BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR-BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181). CONCLUSION: Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity. FUNDING: Bristol-Myers Squibb. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01793103.
29447542 Predictors for orthopaedic surgery in patients with rheumatoid arthritis: results from a r 2018 Jul OBJECTIVES: To investigate how patient characteristics, time of diagnosis, and treatment affect the need for orthopaedic surgery in patients with rheumatoid arthritis (RA). METHOD: We reviewed the medical history of 1544 patients diagnosed with RA at Haukeland University Hospital in Bergen, Norway, from 1972 to 2009, of whom 1010 (mean age 57 years, 69% women) were included in the present study. Relevant orthopaedic procedures were obtained from the Norwegian Arthoplasty Register and the hospital's administrative patient records. In total, 693 procedures (joint synovectomies 22%, arthrodeses 21%, prostheses 41%, and forefoot procedures 12%) were performed in 315 patients. Survival analyses were completed to evaluate the impact of different factors such as age, gender, radiographic changes, and year of diagnosis, on the risk of undergoing surgery. RESULTS: Patients diagnosed in 1972-1985 and 1986-1998 had a relative risk of undergoing surgery of 2.4 and 2.2 (p < 0.001), respectively, compared to patients diagnosed in 1999-2009. Radiographic changes at diagnosis and female gender were also significant risk factors. Anti-rheumatic medication was significantly different in the three time periods. CONCLUSION: Patients with a diagnosis in the early years had a greatly increased risk of having orthopaedic surgery performed. This is probably due to the year of diagnosis being a proxy for the type and intensity of medical treatment.
30421014 Automatic quantification of tenosynovitis on MRI of the wrist in patients with early arthr 2019 Aug OBJECTIVES: Tenosynovitis (inflammation of the synovial lining of the sheath surrounding tendons) is frequently observed on MRI of early arthritis patients. Since visual assessment of tenosynovitis is a laborious task, we investigated the feasibility of automatic quantification of tenosynovitis on MRI of the wrist in a large cohort of early arthritis patients. METHODS: For 563 consecutive early arthritis patients (clinically confirmed arthritis ≥ 1 joint, symptoms < 2 years), MR scans of the wrist were processed in three automatic stages. First, super-resolution reconstruction was applied to fuse coronal and axial scans into a single high-resolution three-dimensional image. Next, 10 extensor/flexor tendon regions were segmented using atlas-based segmentation and marker-based watershed. A measurement region of interest (ROI) was defined around the tendons. Finally, tenosynovitis was quantified by identifying image intensity values associated with tenosynovial inflammation using fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within the measurement ROI. A subset of 60 patients was used for training and the remaining 503 patients for validation. Correlation between quantitative measurements and visual scores was assessed through Pearson correlation coefficient. RESULTS: Pearson correlation between quantitative measurements and visual scores across 503 patients was r = 0.90, p < 0.001. False detections due to blood vessels and synovitis present within the measurement ROI contributed to a median offset from zero equivalent to 13.8% of the largest measurement value. CONCLUSION: Quantitative measurement of tenosynovitis on MRI of the wrist is feasible and largely consistent with visual scores. Further improvements in segmentation and exclusion of false detections are warranted. KEY POINTS: • Automatic measurement of tenosynovitis on MRI of the wrist is feasible and largely consistent with visual scores. • Blood vessels and synovitis in the vicinity of evaluated tendons can contribute to false detections in automatic measurements. • Further improvements in segmentation and exclusion of false detections are important directions of future work on the path to a robust quantification framework.
27810462 Direct medical costs and their predictors in the EMAR-II cohort: "Variability in the manag 2018 Jan OBJECTIVE: To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve. METHODS: A cross-sectional study was performed in a sample including all regions and hospitals throughout the country. Sociodemographic data, disease activity parameters and treatment data were obtained. Resource utilization for two years of study was recorded and we made costs imputation. Correlation analyzes were performed on all RA patients and those treated with biological and biological naïve, to estimate the differences in resource utilization. Factors associated with increased resources utilization (costs) attending to treatment was analyzed by linear regression models. RESULTS: We included 1,095 RA patients, 26% male, mean age of 62±14 years. Mean of direct medical costs per patient was €24,291±€45,382. Excluding biological drugs, the average cost per patient was €3,742±€3,711. After adjustment, factors associated with direct medical costs for all RA patients were biologic drugs (P=.02) and disease activity (P=.004). In the biologic-naïve group, the predictor of direct medical costs was comorbidity (P<.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007). CONCLUSION: Our data show a remarkable economic impact of RA. It is important to identify and estimate the economic impact of the disease, compare data from other geographic samples and to develop improvement strategies to reduce these costs and increase the quality of care.
28438483 What role does rheumatoid arthritis disease activity have in cardiovascular risk? 2018 Nov Rheumatoid arthritis (RA) is associated with a 1.3 to 3-fold increase in mortality, being the major cause of death from cardiovascular complications (40%-50%). Therefore, the initial approach should include cardiovascular risk (CVR) assessment using algorithms adapted for this population. Although, SCOREM is an important advance, there are data indicating that subclinical atherosclerosis may be underdiagnosed. OBJECTIVE: To estimate the strength of association between carotid ultrasound and SCOREM in this population, as well as the implication of disease activity. METHODOLOGY: Cross-sectional, observational, analytical study performed at the General Hospital of Ciudad Real, Spain, between June 2013 and May 2014. The evaluation of CVR was performed and, according to SCOREM, the population was divided into low and high (medium, high and very high) risk. We studied the presence of subclinical atherosclerosis in low-risk patients. RESULTS: Of the total of 119 RA patients, 73.1% had traditional risk factors. Thirty-eight patients were excluded because of a previous cardiovascular event, diabetes mellitus and/or nephropathy. Atheromatous plaque was observed in 14.63% of the low-risk population. The factor with the strongest association to the presence of subclinical atherosclerosis was a moderate or high activity of RA measured by the simplified disease activity index with an odds ratio of 4.95 (95% CI: 1.53-16.01). CONCLUSIONS: Although there was an acceptable correlation between the presence of subclinical atherosclerosis and SCOREM, there was a considerable proportion of atheromatous plaques in low-risk patients. Disease activity was the risk factor most closely associated with increased CVR.
29282619 Dickkopf 1 protein circulating levels as a possible biomarker of functional disability and 2018 Mar Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint destruction, deformity, lower functionality, and decrease in life expectancy. Wingless signaling pathway (Wnt) has been recently involved in bone homeostasis. Studies suggest that overexpression of the pathway inhibitors, like the Dickkopf 1 protein (DKK1), has been implicated in bone destruction. The objective of this study is to compare circulating levels of DKK1 in different groups of patients with disease activity (remission, low, moderate, high activity,) and functionality status. Three hundred seventy-nine patients with RA were evaluated between March 2015 and November 2016. Disease activity was evaluated by disease activity score 28 with C-reactive protein (DAS28CPR), simplified and clinical disease activity scores (SDAI, CDAI), routine assessment of patient index data 3 (RAPID3), functional status using Multidimensional Health Assessment Questionnaire (MD-HAQ), and the Steinbrocker functional classification. DKK1 levels were measured by ELISA. The mean age was 60.7 ± 13.9 years. Disease duration was 13.2 ± 10.9 years. Higher levels of DKK1 were not associated with disease activity by CDAI (p = 0.70), SDAI (p = 0.84), DAS28CRP (p = 0.80), or RAPID3 (p = 0.70). Interestingly higher levels of DKK1 were significantly associated to lower functional status evaluating by the Steinbrocker classification (p = 0,013), severe disability by MD-HAQ (p = 0,004), and variables associated with joint destruction like osteoporosis, higher titles of rheumatoid factor, smoking, and increased hospital admissions related to RA. Higher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity by CDAI, SDAI, DAS28, and RAPID3. This could be explained by more structural damage; DKK1 could be used as a biomarker of joint destruction in RA.
30297331 Identification of a distinct imaging phenotype may improve the management of palindromic r 2019 Jan OBJECTIVES: To use high-resolution imaging to characterise palindromic rheumatism (PR) and to compare the imaging pattern observed to that seen in new-onset rheumatoid arthritis (NORA). METHODS: Ultrasound (US) assessment of synovitis, tenosynovitis and non-synovial extracapsular inflammation (ECI) was performed during and between flares in a prospective treatment-naive PR cohort. MRI of the flaring region was performed where possible. For comparison, the same US assessment was also performed in anticyclic citrullinated peptide (CCP) positive individuals with musculoskeletal symptoms (CCP+ at risk) and patients with NORA. RESULTS: Thirty-one of 79 patients with PR recruited were assessed during a flare. A high frequency of ECI was identified on US; 19/31 (61%) of patients had ECI including 12/19 (63%) in whom ECI was identified in the absence of synovitis. Only 7/31 (23%) patients with PR had synovitis (greyscale ≥1 and power Doppler ≥1) during flare. In the hands/wrists, ECI was more prevalent in PR compared with NORA and CCP+ at risk (65% vs 29 % vs 6%, p<0.05). Furthermore, ECI without synovitis was specific for PR (42% PR vs 4% NORA (p=0.003) and 6% CCP+ at risk (p=0.0012)). Eleven PR flares were captured by MRI, which was more sensitive than US for synovitis and ECI. 8/31 (26%) patients with PR developed RA and had a similar US phenotype to NORA at progression. CONCLUSION: PR has a distinct US pattern characterised by reversible ECI, often without synovitis. In patients presenting with new joint swelling, US may refine management by distinguishing relapsing from persistent arthritis.
29020148 Childhood Residential and Agricultural Pesticide Exposures in Relation to Adult-Onset Rheu 2018 Feb 1 Farming and pesticide exposure may influence risk of rheumatoid arthritis (RA); the role of early-life pesticide exposure is unknown. The Sister Study includes a US national cohort of women aged 35-74 years (enrolled 2004-2009); we examined childhood pesticide exposure in women in this cohort with adult-onset RA. Cases (n = 424) were compared with 48,919 noncases. Data included pesticide use at the longest childhood residence through age 14 years, farm residence of at least 12 months with agricultural pesticide exposure through age 18 years, and maternal farm experience. Odds ratios and 95% confidence intervals were adjusted for age, race or ethnicity, education, smoking, and childhood socioeconomic factors. Cases with RA reported more frequent and direct (personal) residential pesticide use in childhood (for infrequent/indirect pesticide use, odds ratio (OR) = 1.1; for frequent/direct use, OR = 1.8; P for trend = 0.013). Compared with women without residential farm history, odds of having RA increased for those reporting a childhood-only farm residence with personal exposure to pesticides used on crops (OR = 1.8, 95% confidence interval: 1.1, 2.9) or livestock (OR = 2.0, 95% confidence interval: 1.2, 3.3). Our findings suggest adult-onset RA may be related to childhood exposure to residential and agricultural pesticides, and support further investigations of lifetime pesticide use in RA.
29487382 Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumat 2018 Feb 27 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay. One peptide, only found in a single strain (AG876), obtained a sensitivity and specificity of 77% and 95%, respectively and showed high sequence similarity to the filaggrin peptide originally used for ACPA detection. Comparison of antibody reactivity to commercial assays found that the citrullinated peptide was as effective in detecting ACPA as highly sensitive and specific commercial assays. The data presented demonstrate that the citrullinated EBNA-2 peptide indeed is recognised specifically by RA sera and that the single peptide is able to compete with assays containing multiple peptides. Furthermore, it could be hypothesized that RA may be caused by (a) specific strain(s) of EBV.
29701040 [Clinical therapeutic effects on rheumatoid arthritis treated with the assisted therapy of 2018 Mar 12 OBJECTIVE: To evaluate the clinical therapeutic effects and safety on rheumatoid arthritis (RA) treated with acupuncture at the points detected with thermosensitive moxibustion in Zhuang medicine combined with western medication. METHODS: A total of 168 RA patients in compliance with the inclusive criteria were collected and randomized into an observation group and a control group, 84 cases in each one. In the control group, in reference to the updated guideline of new drugs by the European League Against Rheumatism (EULAR) in 2013, the medication scheme was formulated for oral administration, methotrexate tablet 7.5 mg, once a week; salazosulfapyridine enteric-coated tablets, 100 mg, twice a day; hydroxychloroquine sulfate tablets, 20 mg, twice a day; and meloxicam tablets, 15 mg, once a day. In the observation group, besides the treatment as the control group, the acupuncture therapy at the points detected with thermosensitive moxibustion in Zhuang medicine was given. The mild moxibustion was applied near to the affected joint with the moxa material of Zhuang herbal medicine to detect the sensitization points. Afterwards, the acupuncture technique of Zhuang medicine was given on those points, without any manipulation applied. The needles were retained for 30 min, once daily. The treatment for 2 weeks was as one course, continuously for 2 courses. The indexes were observed before and after treatment in the two groups including gripping power, the time of morning stiffness, the swollen joint count 28 (SJC 28), the tender joint count 28 (TJC 28), the disease activity score 28 (DAS 28), the score of patient global assessment of disease activity (PtGA) and the score of provider global assessment of disease activity (PhGA), as well as rheumatoid factors (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-cyclic peptide containing citrulline (A-CCP). The clinical therapeutic effects were evaluated in the two groups. RESULTS: After 4-week treatment, a total of 163 patients accomplished the clinical trial, 81 cases in the observation group and 82 cases in the control group. The results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, RF, CRP, ESR and A-CCP were all improved as compared with those before treatment (all P<0.05). In 4 weeks of treatment, the results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, as well as CRP and ESR in the observation group were better than those in the control group (all P<0.05). The results of RF and A-CCP were not different significantly between the two groups (both P>0.05). The total effective rate was 85.19% (69/81) in the observation group, higher than 70.73% (58/82) in the control group (P<0.05). CONCLUSION: The acupuncture therapy at the points detected with thermosensitive moxibustion in Zhuang medicine achieves the satisfactory clinical effects with few adverse effects.
30587230 Effect of high-intensity interval training on muscle remodeling in rheumatoid arthritis co 2018 Dec 27 BACKGROUND: Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skeletal muscle cytokines, and muscle myostatin in patients with RA and prediabetes before and after a high-intensity interval training (HIIT) program. METHODS: Previously sedentary persons with either RA (n = 12) or prediabetes (n = 9) completed a 10-week supervised HIIT program. At baseline and after training, participants underwent body composition (Bod Pod(®)) and cardiopulmonary exercise testing, plasma collection, and vastus lateralis biopsies. Plasma galectin-3, muscle cytokines, muscle interleukin-1 beta (mIL-1β), mIL-6, mIL-8, muscle tumor necrosis factor-alpha (mTNF-α), mIL-10, and muscle myostatin were measured via enzyme-linked immunosorbent assays. An independent cohort of patients with RA (n = 47) and age-, gender-, and body mass index (BMI)-matched non-RA controls (n = 23) were used for additional analyses of galectin-3 inter-relationships. RESULTS: Exercise training did not reduce mean concentration of galectin-3, muscle cytokines, or muscle myostatin in persons with either RA or prediabetes. However, training-induced alterations varied among individuals and were associated with cardiorespiratory fitness and body composition changes. Improved cardiorespiratory fitness (increased absolute peak maximal oxygen consumption, or VO(2)) correlated with reductions in galectin-3 (r = -0.57, P = 0.05 in RA; r = -0.48, P = 0.23 in prediabetes). Training-induced improvements in body composition were related to reductions in muscle IL-6 and TNF-α (r < -0.60 and P <0.05 for all). However, the association between increased lean mass and decreased muscle IL-6 association was stronger in prediabetes compared with RA (Fisher r-to-z P = 0.0004); in prediabetes but not RA, lean mass increases occurred in conjunction with reductions in muscle myostatin (r = -0.92; P <0.05; Fisher r-to-z P = 0.026). Subjects who received TNF inhibitors (n = 4) or hydroxychloroquine (n = 4) did not improve body composition with exercise training. CONCLUSION: Exercise responses in muscle myostatin, cytokines, and body composition were significantly greater in prediabetes than in RA, consistent with impaired muscle remodeling in RA. To maximize physiologic improvements with exercise training in RA, a better understanding is needed of skeletal muscle and physiologic responses to exercise training and their modulation by RA disease-specific features or pharmacologic agents or both. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02528344 . Registered on August 19, 2015.
30132973 The expression levels of long noncoding RNAs lnc0640 and lnc5150 and its gene single-nucle 2018 Dec OBJECTIVES: The aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single-nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients. METHODS: The expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real-time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP-genotyping assays in 627 RA patients and 590 controls. RESULTS: The lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P < 0.001) compared to controls. There were significant associations of lnc0640 and lnc5150 levels with C-reactive protein in RA patients (P = 0.011 and P = 0.014, respectively), while lnc5150 level was associated with erythrocyte sedimentation rate (P = 0.022). TT genotype of rs13039216 in lnc0640 gene was statistically associated with a reduced risk of RA (TT vs CC; P = 0.046), and a decreased risk of rs13039216 variant was observed under the recessive model (P = 0.038). In addition, the G allele of rs141561256 polymorphism in lnc5150 gene was significantly associated with rheumatoid factor in RA patients (P = 0.034). There were no associations between lnc0640 and lnc5150 levels and their respective genotype in RA patients. CONCLUSIONS: The expressions of lnc0640 and lnc5150 were alternated in the RA patients, suggesting that these lncRNAs may involve in the development of RA.
29574040 Epigenetics as biomarkers in autoimmune diseases. 2018 Nov Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis. Therefore, biomarkers that have both high sensitivity and high specificity for diagnosis, reflect disease activity and predict drug response are necessary. An increasing number of publications have proposed the abnormal epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this review will comprehensively summarize the epigenetic progress in the pathogenesis of autoimmune disorders and unearth potential biomarkers that might be appropriate for disease diagnosis and prediction.
30600953 Urinary Orosomucoid - 2 and Soluble CD14 as Potential Biomarkers for Assessment of Disease 2018 Jun Rheumatoid arthritis (RA) is the most common inflammatory joint disease leading to severe disability and premature mortality. Current blood biomarkers for assessing RA activity are invasive and are not highly sensitive or specific to changes in disease activity. Therefore, there is a need for new biomarkers that can accurately indicate disease activity. The present study evaluated the use of urinary orosomucoid (ORM) - 2 and soluble CD14 (sCD14) as non-invasive biomarkers for precise assessment of disease activity of RA, in order to improve treatment outcomes in RA patients. The study included 36 female patients with RA, were divided into three groups of mild, moderate and severe disease activity according to disease activity score 28 (DAS 28) based on erythrocyte sedimentation rate (ESR) and were compared to control group. Urinary levels of ORM-2 and sCD14 were measured by ELISA. All patients showed significant increase in urinary ORM-2 and sCD14 levels in comparison to controls. There were significant positive correlations of urinary ORM-2 and sCD14 levels with DAS28score and also with the conventional blood biomarkers (C- reactive protein (CRP) and ESR). The receiver operating characteristic curve analysis revealed that both urinary ORM-2 and sCD14 have higher predictive value for disease activity than CRP and ESR. In conclusion, Urinary ORM-2 and sCD14 levels were increased in patients with RA and were correlated with the disease activity. Thus, the urinary biomarkers might be able to replace blood measures for RA activity as they could provide non-invasive and precise assessment of disease activity in RA patients.
30049830 Huntingtin-interacting protein 1 (HIP1) regulates arthritis severity and synovial fibrobla 2018 Nov OBJECTIVES: While new treatments for rheumatoid arthritis (RA) have markedly improved disease control by targeting immune/inflammatory pathways, current treatments rarely induce remission, underscoring the need for therapies that target other aspects of the disease. Little is known about the regulation of disease severity and joint damage, which are major predictors of disease outcome, and might be better or complementary targets for therapy. In this study, we aimed to discover and characterise a new arthritis severity gene. METHODS: An unbiased and phenotype-driven strategy including studies of unique congenic rat strains was used to identify new arthritis severity and joint damage genes. Fibroblast-like synoviocytes (FLS) from rats and patients with RA expressing or not Huntingtin-interacting protein 1 (HIP1) were studied for invasiveness, morphology and cell signalling. HIP1 knockout mice were used in in vivo confirmatory studies. Paired t-test was used. RESULTS: DNA sequencing and subcongenic strains studied in pristane-induced arthritis identified a new amino acid changing functional variant in HIP1. HIP1 was required for the increased invasiveness of FLS from arthritic rats and from patients with RA. Knocking down HIP1 expression reduced receptor tyrosine kinase-mediated responses in RA FLS, including RAC1 activation, affecting actin cytoskeleton and cell morphology and interfering with the formation of lamellipodia, consistent with reduced invasiveness. HIP1 knockout mice were protected in KRN serum-induced arthritis and developed milder disease. CONCLUSION: HIP1 is a new arthritis severity gene and a potential novel prognostic biomarker and target for therapy in RA.
29867985 Anti-Inflammatory Effects of HDL in Mice With Rheumatoid Arthritis Induced by Collagen. 2018 OBJECTIVE: To investigate the anti-inflammatory effects of high-density lipoprotein (HDL) in mice with rheumatoid arthritis (RA) induced by collagen. METHODS: Male DBA/1 mice (8-week-old) were divided into three groups: control (treated with saline), collagen-induced arthritis (CIA), and CIA + HDL. CIA was induced with bovine type II collagen, and after the injection of bovine type II collagen, the CIA + HDL group received an injection of HDL on day 28 followed by HDL injections four times every 3 days. Mice were weighed, the paws were scored, and paw thickness was measured beginning on day 21. Additionally, the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 were measured by ELISA kits, tissue sections of paws were stained with hematoxylin and eosin, and the inflammatory signaling pathway was analyzed by western blotting. RESULTS: We found that the production of pro-inflammatory cytokines TNF-α and IL-6 in mice which received HDL decreased 45.14 and 35.02%, respectively. And we also found that HDL could significantly decrease the level of anti-type-II-collagen IgG2a and inhibit the neutrophil infiltration and cell proliferation and protect the ankle joint from type II collage-induced injury. Western blot analysis indicated that HDL could also inhibit the activation of the NF-κB, MAPK, and ERK signaling pathways in RA mice. CONCLUSION: HDL can inhibit the inflammation induced by bovine type II collagen and the development of RA.
29416134 The B cell response to citrullinated antigens in the development of rheumatoid arthritis. 2018 Mar The immune response to citrullinated antigens is found almost exclusively in patients with rheumatoid arthritis (RA). It is a dynamic response that expands before the onset of disease and generates antibodies (anti-citrullinated protein antibodies (ACPAs)) that are extensively glycosylated in the variable domain. This feature of ACPAs is remarkable and warrants detailed investigation, as it can offer insights into the earliest immunologic mechanisms that lead up to the development of RA. The acquisition of variable domain glycans, in fact, could enable ACPA-expressing B cells to breach tolerance. Although the underlying mechanisms are still elusive, data to support this concept are emerging, owing to the reliable identification and isolation of citrullinated antigen-directed B cells from patients with RA. This technological proficiency also allows for the generation of an increasing number of well-defined monoclonal ACPAs, and provides the opportunity to test and define the mechanisms by which the citrullinated antigen-directed B cell response contributes to the onset and persistence of inflammation. Together with a revised perception of the HLA-risk effect and novel insights into how T cells can govern antibody effector functions, these developments shape an increasingly clear picture of the B cell response to citrullinated antigens in the development of RA.
29412042 Musculoskeletal pain and menopause. 2018 Mar Musculoskeletal pain, arthralgia and arthritis are all more common in women, and their frequency increases with age and in some appears to be associated with the onset of menopause. The clinical assessment, investigation and management of women presenting with musculoskeletal pain, arthralgia or arthritis at the time of menopause are reviewed. Common causes of arthralgia and arthritis in this population are discussed. The epidemiological and trials evidence for the effects of hormone replacement therapy on musculoskeletal pain and arthritis (primarily from RCTs of HRT for other menopausal symptoms) are discussed. Lastly, the possible underlying aetiological roles of sex hormones including estrogen, and their deficiency, in predisposing to musculoskeletal pain and arthritis are overviewed. Although the association appears strong, a causal link between estrogen deficiency and musculoskeletal pain or different types of arthritis is lacking; there have been few studies specifically within this group of symptomatic patients, and there is much still to understand about musculoskeletal pain and arthritis at the time of the menopause, and about how we might prevent or treat this.