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ID PMID Title PublicationDate abstract
28446218 Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while 2017 Apr 26 BACKGROUND: Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. METHODS: One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. RESULTS: Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 μg/l, interquartile range (IQR) 3.8-5.5) versus non-RA (4.0 μg/l, IQR 3.1-4.9; p = 0.03) and controls (3.8 μg/l, IQR 3.0-4.8; p = 0.009). PIIANP was equally depressed in either subset (p < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3 + anti-CCP increased to 0.71 (95% CI 0.59-0.83). CONCLUSIONS: Galectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA. TRIAL REGISTRATION: KF 11 315829. Registered 25 July 2006.
28112584 Association of Fcgamma receptor type 2A and 3A genotypes with rheumatoid arthritis in Chin 2017 Feb AIM: SNPs of FcγRs were implicated in pathogenesis of rheumatoid arthritis (RA) and treatment efficacy of TNF inhibitors (TNFi). This study aims to investigate the associations of FcγRIIa and FcγRIIIa genotypes with autoantibody production and treatment response to TNFi in Chinese patients with RA. PATIENTS & METHODS: FcγRIIa and FcγRIIIa polymorphisms were genotyped in 158 RA patients. Response to TNFi was evaluated in 18 patients at 3 and 6 months after treatment. RESULTS: FcγRIIa-131H allele was significantly increased in autoantibody-negative RA patients. FcγRIIa-131H/H+H/R was closely associated with differences in 28-joint disease activity score in patients at months 3 and 6 of TNFi treatment. CONCLUSION: FcγRIIa-131H allele may have a protective role in autoantibody production and might be a biomarker for predicting good response to TNFi in Chinese RA patients.
29039504 Inhibitory effects of ubiquitination of synoviolin by PADI4. 2017 Dec Rheumatoid arthritis (RA) is a chronic inflammatory articular disease that is characterized by synovial hyperplasia. A number of signaling pathways are associated with the development and induced symptoms of RA. Notably, patients with RA have increased protein citrullination and generation of auto‑antibodies against citrullinated proteins. Genome wide association studies have revealed that peptidyl‑arginine deiminase 4 (PADI4) is an enzyme implicated in citrullination in the RA synovium. Autoantibodies targeting citrullinated proteins are used as diagnostic markers in patients with RA. The functions associated with citrullinated proteins are thought to induce autoimmunity, however, the regulatory mechanisms of citrullination via PADI4 are unclear. The group has previously cloned an E3 ubiquitin ligase, synoviolin (SYVN1), from the RA synovium, demonstrating that SYVN1 serves critical roles in synovial hyperplasia. The data indicated that the endoplasmic reticulum (ER) associated degradation system, which involves SYVN1, may have important roles in the proliferation of synoviocytes. In addition, ubiquitination by SYVN1 is associated with fibrosis, inflammation and cytokine production via the regulation of ER stress signals and quality control of proteins. The present study investigated the crosstalk between the representative post‑translational signaling processes, citrullination and ubiquitination. The results revealed that PADI4 interacted with SYVN1 directly and that overexpression of PADI4 suppressed the ubiquitination of proteins. Thus, a reduction in ER stress induced by PADI4 may abrogate the initiation of chronic RA by suppressing the proliferative signals of RA synoviocytes.
28898138 Redox-sensitive transcription factors play a significant role in the development of rheuma 2018 May 4 Rheumatoid arthritis (RA) is a chronic autoimmune disease which is associated with significant morbidity. Redox sensitive transcription factors including NF-κB, HIF, AP-1, and Nrf2 are intimately involved in the pathogenesis of RA. The treatment of this disease is limited by the elusive nature of the pathogenesis of RA. NF-κB is crucial for the maturation of immune cells as well as production of TNFα and MMPs, which escalate RA. HIF is essential for activation of inflammatory cells, angiogenesis and pannus formation in RA. AP-1 regulates cytokine and MMP production as well as synovial hyperplasia which are key processes in RA. Nrf2 is involved with chondrogenesis, osteoblastogenesis, prostaglandin secretion and ROS production in RA. Targeting two or more of these transcription factors may result in increased efficacy than either therapy in isolation. This review will highlight the control specific mediators on these transcription factors, the subsequent effect of these transcription factors once activated, and then mesh this with the pathogenesis of RA. The elucidation of key transcription factor regulation in the pathogenesis of RA may highlight the novel therapy interventions which may prove to have a greater efficacy than those therapies currently available.
28800441 Digital image analysis protocol for determining the radiocarpal joint space in the rheumat 2017 Oct 1 This paper describes a simple protocol for measuring the joint space of the rheumatoid arthritic (RA) wrist from projection radiographs. The protocol is implemented using a computer algorithm based upon the Interactive Data Language platform. The computerized algorithm features a user-friendly graphical interface to aid the operator to measure joint space parameters, namely distance and area, of the wrist vertebral morphometry at the radiocarpal region. Dual-energy X-ray absorptiometry (DXA) radiograph of a standard hand and wrist phantom was evaluated using the measurement protocol to determine the accuracy and precision of the protocol. The accuracy, parameterised by the systematic error, returned a mean of 5.20% for distance and is equal to 3.49% for area measurement. The precision of the measurement protocol, parameterised by the coefficient of variation (CV), for distance returned a mean of 1.96%; the CV for area measurement equals 2.1%. Three observers participated to investigate the repeatability (intra-observer) and reproducibility (inter-observer) of the measurement protocol, parameterised by the CV, using DXA radiographs from a healthy volunteer and a RA patient. The inter-observer repeatability for distance measurement for the respective observers returned mean values of 10.9%, 7.7% and 11.4% for the healthy wrist. However, the results revealed improved repeatability for the RA wrist; the CV for the respective observers returned mean values of 7.7% 7.1% and 10.0%. The inter-observer repeatability for area measurement for the respective observers returned mean values of 10.2%, 7.1% and 10.1% for the healthy wrist. However, the results revealed improved repeatability (in two out of the three observers) for the RA wrist; the CV for the respective observers returned mean values of 6.8% 6.5% and 10.8%. Student's t-test analysis of the intra-observer repeatability revealed that the measurements of distance and area were generally not intra-observer sensitive. On the other hand, student's t-test analysis of the inter-observer reproducibility revealed that half of the distance measurements were inter-observer sensitive; whereas the remaining were not. Similar findings were obtained for area measurements. Overall the results reveal that the variabilities in accuracy and precision tests and the repeatability and reproducibility tests were typically 10% or less. These findings, in addition to the versatility and simplicity of the digital image analysis protocol, lend to the potential of using the protocol to complement the acquisition of bone mineral density data derived from DXA for diagnosing the progression of RA in patients.
28416828 [Application of bilateral direct anterior approach total hip arthroplasty: a report of 22 2017 Apr 18 OBJECTIVE: To analyze the operation technique and the methods to avoid early complications on the learning curve for bilateral direct anterior approach (DAA) total hip arthroplasty (THA). METHODS: We retrospectively studied a series of continued cases with bilateral avascular necrosis of the femoral head (AVN) or degenerative dysplastic hip and rheumatoid arthritis that were treated by DAA THA in Beijing Jishuitan Hospital. A total of 22 patients with 44 hips were analyzed from June 2014 to August 2016 in this study. There were 17 males and 5 females, and the median age was 48 years (range: 34-67 years). All the surgery was done by DAA method by two senior surgeons. The clinic characters, early surgery treatment results and complications were analyzed. RESULTS: We used the cementless stems in all the cases. The average operating time was (167±23) min; the average blood loss was (775±300) mL;the blood transfusion was in average (327±341) mL; the wound drainage in average was (111±73) mL. Most of the patients could move out of the bed by themselves on the first day after operation, 5 patients could walk without crutches on the first operating day, and 13 patients could squat on the third days after operation. The patients were discharged averagely 4 days after operation. We followed up all the patients for averagely 16 months (range: 8-24 months). There was no loosening or failure case in the latest follow up. In the study, 2 patients had great trochanter fracture, 2 patients had thigh pain, 4 patients had lateral femoral cutaneous nerve palsy, and 3 patients had muscle damage. The Harris scores were improved from 29±8 preoperatively to 90±3 postoperatively (P<0.01). CONCLUSION: The DAA THA can achieve faster recovery and flexible hip joint after operation. However it is a kind of surgery with high technique demanding. Carefully selected patients, and skilled technique, can help the surgeon avoid the early complications. It is associated with high complication rate in the learning curve for bilateral DAA THA.
27539207 Recurrence of deformity after silicone implant and resection arthroplasty of the metatarso 2017 Mar OBJECTIVE: To examine the recurrence of deformity after silicone implant arthroplasty combined with resection arthroplasty for severe forefoot deformity in patients with rheumatoid arthritis. METHODS: We reviewed the long-term results of this procedure for 27 feet in 15 patients. Their average age and disease duration at the time of operation were 58.6 years and 17.5 years, respectively, and the average follow-up period was 10.3 years. RESULTS: An improved hallux valgus angle (45.3° preoperatively, 23.6° 6 months after operation) was maintained. By contrast, deformity and dislocation of lesser toe had recurred at the final follow-up; the angle between the proximal phalanx and the metatarsal of the second toe improved 13.4° with recurrence of 22.5°, the angle between the proximal phalanx and ground surface improved 22.4° with recurrence of 34.5. Furthermore, claw toe deformity at the final follow-up was significantly worse in the group whose hallux valgus deformity was observed 6 months after operation. CONCLUSION: This procedure could maintain the alignment of the first metatarsophalangeal joint, but the recurrence of claw toe deformity is a problem and the relation between the first toe and the lesser toe is an important consideration.
28743355 Rheumatoid arthritis and sleep quality. 2017 Jul BACKGROUND: Sleep disturbances are common in rheumatoid arthritis (RA) patients and contribute to loss of life quality. OBJECTIVE: To study associations of sleep quality with pain, depression and disease activity in RA. METHODS: This is a transversal observational study of 112 RA patients submitted to measurement of DAS-28, Epworth scale for daily sleepiness, index of sleep quality by Pittsburg index, risk of sleep apnea by the Berlin questionnaire and degree of depression by the CES-D (Center for Epidemiologic Studies Depression scale) questionnaire. We also collected epidemiological, clinical, serological and treatment data. RESULTS: Only 18.5% of RA patients had sleep of good quality. In univariate analysis a bad sleep measured by Pittsburg index was associated with daily doses of prednisone (p=0.03), DAS-28 (p=0.01), CES-D (p=0.0005) and showed a tendency to be associated with Berlin sleep apnea questionnaire (p=0.06). In multivariate analysis only depression (p=0.008) and Berlin sleep apnea questionnaire (p=0.004) kept this association. CONCLUSIONS: Most of RA patients do not have a good sleep quality. Depression and risk of sleep apnea are independently associated with sleep impairment.
28535535 Inflammation Is an Important Covariate for the Crosstalk of Sleep and the HPA Axis in Rheu 2017 Rheumatoid arthritis (RA) patients have sleep problems, and inflammation influences sleep. We demonstrated that sleep quality improves during intensified treatment with methotrexate (MTX) or etanercept (ETA). Since the hypothalamic-pituitary-adrenal (HPA) axis is involved in sleep regulation, this study investigated the interrelation between sleep parameters, inflammation as objectified by C-reactive protein (CRP), and serum cortisol and adrenocorticotropic hormone (ACTH) levels. Thirty-one eligible patients (disease activity score, DAS28CRP ≥3.2) participated in a 16-week, open, prospective study of HPA axis outcomes. MTX was initiated in 15 patients (female-to-male ratio 9/6) and ETA in 16 patients (14/2). Clinical, laboratory (after polysomnography [PSG] between 8 and 9 a.m.), sleep (PSG), and HPA axis outcome parameters (after PSG between 8 and 9 a.m.) were recorded at baseline and week 16. Clinical characteristics of patients markedly improved throughout the study (e.g., DAS28CRP: p < 0.001; CRP: p < 0.001). Sleep efficiency and wake time after sleep onset markedly improved in the ETA group. Serum cortisol and ACTH did not change during observation. At baseline, serum cortisol levels were negatively correlated to sleep efficiency; this may depend on inflammation, because controlling for CRP eliminated this negative correlation. After ETA treatment, serum cortisol had a high positive correlation with total sleep time, sleep efficiency, and a negative correlation with wake time before and after sleep onset, which was not eliminated by controlling for CRP. In RA patients, the data indicate that inflammation is an important covariate for the crosstalk of sleep and the HPA axis.
29052023 The serum level and significance of lysyl oxidase-like 2 in patients with rheumatoid arthr 2018 Jan Our previous experiments found that lysyl oxidase-like 2 (LOXL2) may be a useful preclinical serological marker for pulmonary fibrosis in the mouse model. The role of LOXL2 in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is still unclear. We investigated whether serum LOXL2 levels are associated with RA-ILD patients. The levels of serum LOXL2 were measured by enzyme-linked immunosorbent assay in 49 RA-ILD patients (21 patients with ILD disease duration < 3 months; 28 patients with ILD disease duration > 3 months), 43 RA patients without ILD and 20 normal healthy controls. We assessed the correlations between the serum LOXL2 levels and clinical variables. Serum LOXL2 levels were significantly higher in RA patients than in normal healthy controls (326.79 ± 192.56 vs. 53.27 ± 35.86 pg/ml, P < 0.01). No significant difference was present between the RA-ILD group and RA without ILD group (298.87 ± 219.85 vs. 358.60 ± 152.16 pg/ml, P = 0.13). Notably, the serum LOXL2 levels were significantly higher in patients with ILD disease duration < 3 months than in those with ILD disease duration > 3 months (462.71 ± 208.97 vs. 175.99 ± 130.55 pg/ml, P < 0.01) or without ILD (462.71 ± 208.97 vs. 358.60 ± 152.16 pg/ml, P = 0.03). The serum LOXL2 levels in RA-ILD patients significantly correlated with DAS28 (r(s) = 0.31, P = 0.034), C-reactive protein (r(s) = 0.41, P = 0.004), rheumatoid factor (r(s) = 0.41, P = 0.003), forced vital capacity (r(s) = - 0.39, P = 0.02), and diffusion capacity of the lung for carbon monoxide (r(s) = - 0.44, P = 0.009). LOXL2 may be involved in the pathogenesis of rheumatoid arthritis-associated interstitial lung disease and might be helpful in early diagnosis of RA-ILD.
29234911 Increased DOT1L in synovial biopsies of patients with OA and RA. 2018 May The studies aimed to determine the changes of histone methylation in synovial tissues of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Synovial tissues were obtained from 30 patients including 12 OA, 16 RA, and 2 trauma that were used as control. A histone methyltransferase DOT1L of the tissues was examined for transcript level with quantitative RT-PCR and protein expression with western blot. Methylation status of DOT1L substrate, H3K79, was examined with immunohistochemistry and western blot. Two-tailed non-pair T test and chi-square test were applied for age/disease duration and gender distribution, respectively. Kruskal-Wallis test and Post hoc Dunn's test were used for examine the difference between control, OA and RA. Both transcript and protein levels of DOT1L appeared the highest in synovial tissues of RA patients and increased in that of OA patients compared to the controls with ratios of 13.8/4.7/1 and 15.5/11.2/1.0 for RA/OA/control, respectively. The changes between RA and control, and RA and OA patients were statistically significant. Both immunohistochemistry study and western blot showed an increased methylation of H3K79 in synovial tissues of OA and RA patients. Gene and protein expression of DOT1L was increased in synovial tissues of both OA and RA patients. A high level of di-methylated H3K79 was also observed in the patients. Considering the important functions of DOT1L and H3K79 contributing to the initiation and maintenance of active transcription in the genome, these unprecedented findings, although still unclear how to impact diseases, may provide novel insights to further explore pathological mechanism of OA and RA.
28160488 Atherosclerosis is not accelerated in rheumatoid arthritis of low activity or remission, r 2017 Jun 1 OBJECTIVES: RA associates with increased cardiovascular disease (CVD) morbidity and mortality due to accelerated atherosclerosis, attributed to both classical risk factors and chronic inflammation. The aim of this study was to test the hypothesis that effective disease control over 3 years modifies acceleration of atherosclerosis in RA. METHODS: Consecutive, non-diabetic RA patients previously examined by ultrasonography for subclinical atherosclerosis were re-evaluated after 3.2 (0.2) years, provided that they were in remission/low disease activity (DAS28 <3.2) for at least 75% of this period. Patients (n = 139) were demographically matched with 139 non-diabetic, non-RA control individuals studied in parallel. RESULTS: Patients and controls (mean age of 56 years at baseline) had a comparable burden of classical CVD risk factors. Patients' pulse wave velocity (reflecting arterial stiffness) changed by 0.07 m/s/year and left carotid intima-media thickness (reflecting wall hypertrophy) increased by 0.009 mm/year; formation of new atheromatic plaques in carotid and/or femoral arterial beds occurred in 22%. Multivariate analysis after correcting for all classical CVD risk factors and anti-hypertensive/lipid-lowering therapies demonstrated no significant differences between patients and controls in any of the subclinical atherosclerosis indices. Changes in all atherosclerosis indices from baseline to end of follow-up were comparable between those 56 patients treated with biologic DMARDs and their demographically matched patients treated with synthetic DMARDs. CONCLUSION: Effective disease control may abrogate any RA-specific effect on the progression of atherosclerosis regardless of treatment. Whether early and sustained RA control translates to the CVD outcomes expected in the general population should be examined in prospective studies.
28079508 Management of dyslipidaemia in high-risk patients with recent-onset rheumatoid arthritis: 2017 Mar OBJECTIVES: Reduction of LDL-cholesterol (LDLc) is essential to decrease the cardiovascular mortality in rheumatoid arthritis (RA). Between 2005 and 2010, French recommendations for dyslipidaemia defined the LDLc target based on the number of cardiovascular risk factors. In 2006, it was recommended to consider LDLc objectives with RA being counted as an additional cardiovascular risk factor. Our objective was to assess lipid target achievement between 2006 and 2010 in a cohort of patients with recent-onset RA. METHODS: 814 patients were included between 2002 and 2005 in a French cohort of patients with early arthritis and a high probability of RA (ESPOIR). Repeated cross-sectional analyses for cardiovascular risk factors, cholesterol levels were performed every year from 2006 to 2010 to determine lipid profile and achievement of the LDLc goal according to the French guidelines. RESULTS: On the 620 patients analysed at the first point, 77% were female, 89.8% fulfilled the ACR criteria for RA and 2.7% received a statin. The proportion of patients failing to achieve the LDLc target did not improve following the publication of specific RA guidelines in 2006 (15.3 to 22.5% between 2006 and 2010). In patients with the highest cardiovascular risk, more than 58% did not reach the LDLc target. CONCLUSIONS: Specific recommendations for RA published in 2006 decreased LDLc target but did not improve management of dyslipidaemia in daily life which remained suboptimal particularly in patients at highest risk.
28936606 Denosumab significantly improves bone mineral density with or without bisphosphonate pre-t 2017 Sep 21 Bone mineral density (BMD) sometimes cannot be improved by long-term bisphosphonate (BP) therapy in osteoporosis (OP) patients with rheumatoid arthritis (RA). This study showed that BMD significantly increased after denosumab treatment in patients with long-term BP pre-treatment as much as in treatment-naïve patients. Thus, denosumab can be a strong OP treatment option for long-term BP pre-treated RA patients. INTRODUCTION: The aim of this 24-month retrospective study was to evaluate differences in outcomes of denosumab with or without bisphosphonate (BP) pre-treatment in osteoporosis (OP) patients with rheumatoid arthritis (RA). METHODS: Patients were divided into those with (BP group, 26 cases) or without (denosumab group, 26 cases) BP pre-treatment. We measured serum BAP, TRACP-5b, and urinary NTX at baseline and every 3 months for 24 months. We also assessed bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and total hip BMD (H-BMD) at baseline and every 6 months for 24 months. MMP-3, DAS28-CRP, SDAI, and HAQ-DI were assessed at baseline and 24 months to evaluate RA state. RESULTS: In BP group, the percent changes of bone turnover markers decreased but were consistently higher compared with those in the denosumab group. There were significant differences of the percent changes in BAP at 9, 21, and 24 months; TRACP-5b at 9, 18, and 21 months; and urinary NTX at 3, 9, 12, 15, 18, and 21 months between the groups. The percent changes of L-BMD and H-BMD were significantly increased at 24 months in the BP pre-treated group (11.5 and 13.3%, respectively) and denosumab group (13.0 and 16.5%, respectively). There was a significant difference of the percent changes in H-BMD at 6 months between the groups. There was no significant difference in RA state between the groups. CONCLUSIONS: Compared with BP group, denosumab group displayed significantly increased H-BMD at 6 months, while L-BMD and H-BMD were significantly increased for 24 months in both groups. Thus, regardless of BP pre-treatment, denosumab could be a good agent in OP with RA.
28039541 Patient-reported outcomes in Asia: evaluation of the properties of the Rheumatoid Arthriti 2017 May Patient-reported outcomes (PROs) such as the Europe-developed Rheumatoid Arthritis Impact of Disease (RAID) are important to assess patients' quality of life. Their interpretation may be culture-dependent. To evaluate the potential utility of RAID in multiethnic Asian rheumatoid arthritis (RA) patients. Cross-sectional study of English-speaking RA patients in a Singapore tertiary center. Validity of RAID (scored between 0 and 10 with higher score indicating worse status) was assessed by Spearman's correlation with patient global assessment (PGA), DAS28 and short form 12 (SF-12). Consistency was assessed by Cronbach's alpha and test-retest reliability by intra-class correlation coefficient (ICC) 7 days after (n = 20). Feasibility was assessed by % of missing data. Eighty-two patients were analyzed: median age 53 years (Q1:Q3 44.7; 60.7), disease duration 4.2 years (1.4; 8.8), 66 (81%) women and 54 (66%) Chinese. Although RA was moderately active (median DAS28, 3.2 (2.5; 4.3)), RAID score was very low (median, 1.9 (0.6; 3.7)) with 44 (53.7%) patients having RAID score between 0 and 2. RAID was strongly correlated with PGA (r = 0.75), and moderately with other outcomes (DAS28 r = 0.46, SF12 physical r = -0.45 and SF12 mental r = -0.52, p < 0.0001 for all). Consistency was high (Cronbach's alpha = 0.91). Test-retest reliability was excellent; ICC = 0.84 (95% confidence interval 0.74-0.90). Feasibility was good with only 2 patients with missing data. Despite considerable floor effects, the RAID appeared to be a valid and practical PRO to assess the impact of RA in Asia. Multiethnic Asian patients may underestimate the impact of their disease compared to European patients.
29241640 Association of anti-cyclic citrullinated protein antibodies, erosions, and rheumatoid fact 2018 Apr OBJECTIVES: To evaluate associations between the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) and rheumatoid factor (RF) and other outcomes, including joint erosions and both clinical and economic endpoints, in patients with rheumatoid arthritis (RA). METHODS: Data from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective registry of adult RA patients with established or recent-onset RA, were analyzed. Logistic regression models were constructed to test associations between anti-CCP/RF seropositivity and erosive disease and the presence of anti-CCP/RF seropositivity plus erosive disease and (1) RA severity; (2) hospitalizations; (3) durable medical equipment (DME) use; and (4) worker productivity (e.g., employment status). Covariates in these models included patient age, gender, race, body mass index (BMI), number of comorbidities, and treatment. RESULTS: Among 1309 registrants, those who were positive (vs. negative) for anti-CCP were 2.72 times more likely to have erosions (OR = 2.72; 95% CI: 1.77-4.18; P < 0.001). Individuals positive (vs. negative) for RF were 36% more likely to have erosions (95% CI: 0.88-2.08; P = 0.162). Patients with anti-CCP seropositivity and erosions were significantly more likely to: (1) have higher disease activity as measured by the Disease Activity Score in 28 joints C-reactive protein (DAS28-CRP ≥ 2.6); (2) be hospitalized; (3) use DME; and (4) be unemployed, disabled, or long-term disabled. CONCLUSIONS: For the first time in a "real-world" setting including patients with both recent-onset and chronic RA, this study demonstrated that the combination of anti-CCP seropositivity and erosions were significantly associated with more adverse clinical and health-economic consequences, including a lower probability of low disease activity and higher health resource utilization, despite use of biologic disease-modifying antirheumatic drugs by many patients. This dual presentation may signal a need for more intensive therapies, even when observed in patients with chronic, as well as recent-onset, RA. Trial registration [Brigham and Women's Hospital (BWH) Rheumatoid Arthritis Sequential Study; Registry URL: https://clinicaltrials.gov/ct2/show/NCT01793103; ClinicalTrials.gov Identifier NCT01793103].
27367831 The correlations of socioeconomic status, disease activity, quality of life, and depressio 2017 Jan This study aimed (i) to investigate the relationships among socioeconomic status, disease activity, quality of life, and the psychological status in Chinese rheumatoid arthritis (RA) patients; (ii) to explore the possible risk factors of anxiety and depression. A total of 160 RA patients underwent standardized laboratory examinations and completed several questionnaires. Independent samples t-tests, χ(2) analyses, and logistic regression modeling were used to analyze the data. We found 30.6% RA patients were anxiety, and 27.5% had depression, which were significantly higher than the control group (7.8 and 11.7%, respectively). And there were significant correlations among education, pain, disease activity, medication adherence, functional capacity, quality of life, and anxiety/depression. Meanwhile, logistic regression analysis revealed that poor quality of life and low education level were significantly associated with anxiety/depression in RA patients. In conclusion, there were significant relationships among education, quality of life, and anxiety/depression in Chinese RA patients.
28837666 Tumor necrosis factor-α blockade treatment decreased CD154 (CD40-ligand) expression in rh 2017 CONTEXTS: CD154 (commonly referred to as CD40-ligand) is a critical T cell factor that participates in the pathogenesis of autoimmune and is over-expressed in rheumatoid arthritis (RA). TNF-α blockade treatment had dramatic efficacy in RA. OBJECTIVE: To investigate whether TNF-α blockade treatment can inhibit CD154 expression in RA. METHODS: Blood samples were collected from 33 patients with rheumatoid arthritis before and 3 months after TNF-α blockade treatment. Clinical serological data determined by standard assays and T cell CD154 expression levels determined by flow cytometry were statistically analyzed for these two time points. RESULTS: The percentage of CD154 expression on gated CD4+ T cells of PBMCs from RA patients after 3 months TNF-α blockade treatment was significantly lower than before treatment (2.94 ± 3.21% vs. 7.21 ± 5.64%; p = 0.0001). The disease activity and anti-CCP antibody levels were also significantly reduced after TNF-α blockade treatment. The CD154 expression levels were positively correlated with disease activity index DAS28, and CRP. The post-stimulated CD154 expression percentage of purified CD4+ T cells between baseline and after TNF-α blockade treatment was not significantly different (p = 0.221). Baseline CD154 levels were positively correlated with treatment-induced changes in DAS28 (p = 0.014; r2 = 0.187). CONCLUSIONS: TNF-α blockade treatment significantly decreased the CD154 expression on CD4+ T cells, disease activity and anti-CCP antibody simultaneously in RA patients. However TNF-α blockade did not impair T cell capacity to express CD154 after stimulation. These results suggest that decreased CD154 expression after TNF-α blockade may be due to decreased RA disease activity but not direct inhibition of CD154 responsiveness of T cells.
27636905 Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloa 2017 Jan OBJECTIVE: To describe systemic autoimmune joint diseases that develop following Lyme disease, and to compare their clinical features with those of Lyme arthritis (LA). METHODS: We reviewed records of all adult patients referred to our LA clinic over a 13-year period, in whom we had diagnosed a systemic autoimmune joint disease following Lyme disease. For comparison, records of patients enrolled in our LA cohort over the most recent 2-year period were analyzed. Levels of IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured. RESULTS: We identified 30 patients who had developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease (usually manifested by erythema migrans [EM]). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthritis (SpA). The 30 patients typically had polyarthritis, and those with PsA or SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 patients with LA, the usual clinical picture was monoarticular knee arthritis, without prior EM. Most of the patients with systemic autoimmune joint disorders were positive for B burgdorferi IgG antibodies, as detected by enzyme-linked immunosorbent assay, but had significantly lower titers and lower frequencies of Lyme disease-associated autoantibodies than patients with LA. Prior to our evaluation, these patients had often received additional antibiotics for presumed LA, without benefit. We prescribed antiinflammatory agents, most commonly disease-modifying antirheumatic drugs, resulting in improvement. CONCLUSION: Systemic autoimmune joint diseases (i.e., RA, PsA, SpA) may follow Lyme disease. Development of polyarthritis after antibiotic-treated EM, previous psoriasis, or low-titer B burgdorferi antibodies may provide insight into the correct diagnosis.
29287768 Autoimmune arthritis in Ménière's disease: A systematic review of the literature. 2018 Aug INTRODUCTION: Successful management of patients with Ménière's disease (MD) involves understanding the pathophysiology of the disease and its comorbidities. The role of autoimmune diseases (AD) in MD remains unclear. The aim of this study was to further investigate the association between MD and AD. Specific goals were to characterize the prevalence, distribution, clinical and laboratory findings, and outcomes of autoimmune arthritis (AA) in MD. EVIDENCE REVIEW: This systematic review was conducted according to PRISMA guidelines. Articles were identified through searches of MEDLINE, and EMBASE, as well as manual reviews of references, from 1947 to May 2017. We performed a systematic review of randomized-controlled trials (RCTs) and non-RCTs of cases of AA in MD. Due to the heterogeneity of the study methods and measures, a meta-analysis was not possible and a qualitative synthesis of the literature results was performed. The study protocol was registered with PROSPERO database (Trial Registration: CRD42017070516). FINDINGS: A total of 237 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, nine studies were selected and subjected to a quality assessment. This quality control measure yielded eight studies for analysis in the systematic review. The prevalence of AA was higher in MD (1.0-10.0%) as compared to the general population (0-1.1%), and noted to be higher in patients with familial MD as compared to sporadic MD (16.9% vs 4.5%, p = 0.002). There was no evidence to suggest a difference in immunologic profiles or selected treatment regimens. The most commonly reported AA in patients with MD was rheumatoid arthritis with a mean point prevalence of 4.3%. Many studies did not standardize their diagnostic criteria and did not measure clinically meaningful outcomes. CONCLUSIONS: There is a low level of evidence because of the lack of RCTs and original prospective studies. However, in this systematic review, we have identified the latest point prevalence data on AA in MD, indicating AA to be more prevalent within the MD population. RCTs treating MD as a local AD will enhance our understanding of the disease, and potentially change the way we manage MD.