Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27172254 Multiplex cytokine analyses in patients with rheumatoid arthritis require use of agents bl 2017 Jan OBJECTIVES: Heterophilic antibodies, such as rheumatoid factor (RF), are known to interfere with enzyme-linked immunosorbent assays (ELISAs). Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF)-α blockers is well established. The aims of this study were to develop a protocol for blocking the interaction of present heterophilic antibodies and to validate this procedure by evaluating the effect on correlations of cytokine levels to clinical response in RA patients treated with adalimumab. METHOD: Fourteen patients with active RA were evaluated at baseline and 3 months after starting adalimumab treatment. Cytokines were analysed with a commercial 12-plex bead ELISA. To block interference by RF, a commercial blocker (HeteroBlock) was used. To determine the optimal concentration of HeteroBlock, patient sera were analysed with different concentrations of HeteroBlock. Subsequently, baseline and follow-up sera from the 14 patients were analysed and correlated with clinical outcome. RESULTS: Measured cytokine levels were reduced in the majority of samples when adding the blocker. The optimal concentration of HeteroBlock was 1600 μg/mL of serum. Sera with high RF levels were more prone to produce false positive values, although some RF-negative sera also demonstrated evidence of interference. HeteroBlock did not interfere with the analysis. In RA patients treated with adalimumab, changes in interleukin (IL)-6 levels between baseline and follow-up correlated with changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in sera with added HeteroBlock. CONCLUSIONS: When analysing sera from patients with RA with multiplex bead ELISA, the assay should be evaluated for interference by heterophilic antibodies, and if present corrected with, for example, HeteroBlock.
28874641 Intricate Estimation and Evaluation of Mandibular Movements in Geriatric Patients Sufferin 2017 Sep 1 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder that usually affects joints and making them warm, painful, and swollen. The chief purpose of this study was to evaluate movements of mandible in geriatric patients suffering from RA with or without temporomandibular joint dysfunction. MATERIALS AND METHODS: A total of 45 people were included in this study with age of 60 years and above. Partially or completely edentulous patients were divided into experimental and control group. Experimental group consists of 20 people suffering from arthritis and control group consists of 25 people without arthritis. Movements were recorded with or without prosthesis while mastication in both experimental and control group. RESULTS: Statistical evaluation of two studied groups showed decrease opening angle (p < 0.05) during mastication; however, insertion of new prosthesis showd a significant increase in values in both groups, with an increase in opening and closing angles. CONCLUSION: Positive correlation was found between arthritis and movements of the mandible in older people suffering from RA. CLINICAL SIGNIFICANCE: Patients suffering from RA are having restricted mandibular movements thus imposing an overall negative impact however; presence of prosthesis has been shown to enforce a positive effect on mandibular movement.
29256183 The relationship between the degree of displacement of the atlas to axis and the clinical 2018 Apr INTRODUCTION: The most common type of anatomical cervical spine involvement is atlanto-axial subluxation (AAS) in rheumatoid arthritis (RA). The purpose of this study was to clarify the relationship between the displacement of the atlas to axis and the clinical data obtained in patients with AAS due to RA. METHODS: Fifty patients with AAS due to RA that were treated by surgery are herein reviewed. Based on the findings of preoperative lateral cervical radiographs in the neutral position, the patients were classified into two groups as follows: a 10 + group with an atlanto-dental interval (ADI) of ≧ 10 mm, and a 10 - group with an ADI < 10 mm. RESULTS: Preoperative lateral cervical radiographs demonstrated 15 cases to belong to the 10 + group, while 35 cases belonged to the 10 - group. In the preoperative MR imaging, an intramedullary high signal intensity was observed in seven cases that belonged to the 10 + group and in four cases belonging to the 10 - group. Regarding the neurological severity, the 10 + group included significantly more cases showing severe neurological deficits before surgery; however, there was no significant difference between the two groups regarding the presence of severe deficits even after surgery. CONCLUSIONS: The severe displacement group included significantly more cases showing an intramedullary high signal intensity in the preoperative MR images. Our results also suggest that a severe displacement before surgery affected the presence of neurological deficits before surgery; however, it did not affect the neurological recovery from such severe neurological deficits.
29226727 High expression of interleukine-1 receptor antagonist in rheumatoid arthritis: Association 2017 Dec Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and pro-inflammatory cytokines production. IL-1Ra is an anti-inflammatory cytokine codified by IL1RN gene that blocks IL-1 signalling. A VNTR polymorphism of 86 bp in IL1RN gene has been associated with RA risk and regulation of IL-1Ra expression. In this study, we determined mRNA and protein expression of IL-1Ra in RA patients and control subjects (CS). This study included 85 RA patients classified according to the ACR/EULAR 2010 criteria and 67 CS. Polymerase chain reaction was used to identify IL1RN VNTR polymorphism, the expression of sIL-1Ra (secreted isoform) mRNA was determined by SYBR Green-based real time quantitave-PCR assay, and IL-1Ra soluble levels quantification was evaluated by ELISA test. RA patients had higher soluble levels of IL-1Ra than CS (p < .01), sIL-1Ra mRNA expression was higher in RA patients compared to CS (p < .01). Carriers of IL1RN*2/2 homozygous genotype show increased IL-1Ra soluble levels compared to IL1RN*long/long and IL1RN*2/long genotypes (p < .05) in the CS group, whereas mRNA expression in carriers of IL1RN*2/2 genotype was 1.2 times higher compared to IL1RN*long/long genotypes in the same group. Regarding RA patients, high expression of sIL-1Ra mRNA on carriers of IL1RN*long/long genotype was observed. Nevertheless, in RA patients IL-1Ra soluble levels among genotypes did not show significant differences. High expression of IL-1Ra in RA patients under treatment or not with antirheumatic drugs was detected. Additionally, carriers of IL1RN*2/2 genotype had higher IL-1Ra expression than carriers of other genotypes.
28387872 Identification of significant pathway cross-talk in rheumatoid arthritis by the Monte Carl 2017 Apr 5 We attempted to identify significant pathway cross-talk in rheumatoid arthritis (RA) by the Monte Carlo cross-validation (MCCV) method. We therefore obtained and preprocessed the gene expression profile of RA. MCCV involves identifying differentially expressed genes (DEGs), identifying differential pathways (DPs), calculating the discriminating score (DS) of the pathway cross-talk, and random forest (RF) classification. We carried out 50 bootstrap iterations of MCCV to identify the key instances of pathway cross-talk involved in RA. We identified a total of 17 significant DEGs and 15 significant DPs by comparing RA samples and normal controls. We found the most significant difference between RA and the normal controls in the eIF4 and p70S6K signaling regulation pathway. Furthermore, we identified 10 instances of pathway cross-talk with the best classification performance for RA and normal controls, using the RF classification model. All of the top 10 pathway pairs involved cross-talk with eIF4 and p70S6K signaling regulation, and the other 10 pathways were immune-related. By MCCV, we identified one critical DP and 10 significant instances of pathway cross-talk in RA. We propose that the eIF4 and p70S6K signaling regulation pathway and the other significant instances of pathway cross-talk play key roles in the occurrence and development of RA, and are potential predictive and prognostic markers for RA.
28285445 Differential impact of systemic lupus erythematosus and rheumatoid arthritis on health-rel 2017 Jul PURPOSE: This study examined and compared health-related quality of life (QoL) in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We included patients from two multicentric cohorts, the Swiss SLE cohort study (SSCS) and the Swiss Clinical Quality Management Program for RA (SCQM-RA). Patients were matched by age, sex and disease duration using the propensity score. Disease activity was assessed by SELENA-SLEDAI in SLE and by DAS-28 in RA. QoL was captured by the short-form 36 (SF-36). The primary outcomes were physical component summary (PCS) and mental component summary (MCS) of the SF-36. Generalized estimating equation models were used to assess evolution over time. RESULTS: We analyzed 267 SLE patients and 267 matched RA patients. More patients with RA had active disease and more patients with SLE had immunosuppressant therapies at baseline. The median [interquartile range (IQR)] MCS and PCS scores were 45.1 [33.7-52.6] and 45.6 [38.0-53.0] in SLE and 48.8 [37.6-56.7] and 34.7 [26.8-43.0] in RA, respectively (ps < 0.001). Over one year the differences persisted, although PCS and MCS increased in RA (ps < 0.001) but not in SLE in the univariate analysis. The differences in MCS and PCS scores between RA and SLE remained qualitatively similar after adjustment for patient characteristics, treatment, and activity disease. CONCLUSIONS: SLE and RA both affect QoL. Patients with SLE have lower MCS, whereas patients with RA have lower PCS. These differences remained over 1 year of follow up, suggesting fundamental dissimilarities between SLE and RA in their impact on QoL.
28072711 The coexistence of SAPHO syndrome and rheumatoid arthritis: A case report. 2017 Jan RATIONAL: SAPHO (Synovitis-Acne-Pustulosis-Hyperstosis-Osteitis) syndrome is a rare disease featured by its dermatological and osteoarthritic disorders, the latter of which mainly affecting the anterior chest wall, spine, and sacroiliac joint. However, rheumatoid arthritis (RA) is a chronic autoimmune disease, mainly affecting the synovial tissue of small joints in hands and feet. Here, we present an extremely rare case diagnosed with both SAPHO syndrome and RA, with an onset interval of 10 years. So far, only 1 similar case has been reported in the English literature. PATIENT CONCERNS: In Sep 2015, a 59-year-old female patient presented to our hospital, complaining of refractory low back pain, left sternoclavicular joint pain, and palmoplanar pustulosis (PPP). In addition, RA had been diagnosed 10 years earlier in the patient, manifested as pain and swelling in bilateral hands and wrists, accompanied by morning stiffness, as well as positive serologic tests. INTERVENTIONS: In our hospital, laboratory tests revealed elevated inflammatory markers, and imaging examinations of relevant sites showed specific osteoarthritic lesions for SAPHO syndrome. DIAGNOSES: These findings lead us to make an easy diagnosis of the coexistence of SAPHO syndrome and RA in this petient. OUTCOMES: Treatment with tripterygium wilfordii polyglycosidium and prednisone was introduced. Both dermatological and osteoarthritic symptoms improved during a 3-month follow-up. Symptoms of RA were successfully controlled with prednisone and leflunomide since 2005. LESSONS: We present an extremely rare case diagnosed with both SAPHO syndrome and RA, with an onset interval of 10 years. With this case report, we want to draw attention to the diverse features of SAPHO syndrome.
28646083 Does depression increase the risk of stroke in patients with rheumatoid arthritis? A popul 2017 Jun 22 OBJECTIVES: Comorbid depression is common and undertreated in patients with rheumatoid arthritis (RA). It remains uncertain whether comorbid depression provoked the risk of poor clinical outcome, stroke in particular, among patients with RA. This work aimed to determine if depression onset during the treatment process increases stroke risk for patients with RA as compared with those with (1) neither RA nor depression, (2) RA only and (3) depression only. DESIGN: A nationwide, population-based cohort study. SETTING: Taiwan's Longitudinal Health Insurance Database. PARTICIPANTS: We identified 8045 subjects with a newly diagnosed RA between 1997 and 2010, together with 32 600 subjects without RA matched by age, gender and index date. All subjects were further divided into four groups based on whether they were diagnosed with comorbid depression during the follow-up period. MAIN OUTCOME MEASURE: The incidence rate and HR for incident stroke were estimated by the end of 2012 using Cox proportional hazard regression. RESULTS: We discovered that patients with RA with the comorbid depression exhibited the highest risk of stroke, with an adjusted HR of 2.18 (95% CI 1.87 to 2.54). Those with RA only or those with depression only still had the higher risk of stroke by 43% and 57% as compared with subjects without either condition. Multivariate analysis showed RA subjects who were male or older, incurred the onset of depression, or had comorbidities such as hypertension, diabetes as well as heart disease, had a greater risk of stroke. CONCLUSIONS: This study cleared up the significant association between RA and the subsequent risk of stroke, and further highlighted that the onset of depression within the treatment process may increase stroke risk for RA subjects. Findings could assist healthcare providers to pinpoint individuals with RA with a higher predisposition of stroke, which could facilitate the provision of appropriate rehabilitation.
28160411 Active synovitis in the presence of osteitis predicts residual synovitis in patients with 2018 Oct AIM: To clarify the relationship between active synovitis/osteitis and subsequent residual synovitis (R-synovitis) in patients with rheumatoid arthritis (RA). METHODS: Three hundred and twenty finger joints of 16 patients with active RA at baseline (Disease Activity Score with 28 joints - erythrocyte sedimentation rate > 3.2) who subsequently achieved clinical low disease activity or remission afterwards were analyzed. Synovial vascularity (SV) was assessed according to a semi-quantitative ultrasound score (grades 0-3). Active synovitis was defined by SV positivity at baseline. R-synovitis was defined by the presence of grade > 2 SV at the 24th week. Osteitis was detected by magnetic resonance imaging (MRI) at baseline as trabecular bone lesions with water content and indistinct margins. RESULTS: Ultrasonography detected active synovitis in 116 joints at baseline. Forty-seven joints had R-synovitis at the 24th week. MRI detected osteitis in 12 joints at baseline. The presence of active synovitis with osteitis at baseline was significantly correlated with R-synovitis at the 24th week. CONCLUSIONS: Active synovitis in the presence of osteitis predicted R-synovitis regardless of whether there was a clinical improvement in RA.
26991010 Effect of total knee arthroplasty on other joints in patients with rheumatoid arthritis ev 2017 Jun AIM: The objective of this study was to assess arthritis of the whole body before and after total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) using positron emission tomography (PET). METHOD: Seventeen knees of 17 RA patients (median age 68 years) who underwent TKA were included in this study. Clinical assessments of disease activity, knee function and activities of daily living (ADL) were performed before and after TKA. (18) Fluorodeoxyglucose (FDG)-PET was performed preoperatively and 12 weeks postoperatively when RA disease activity was assessed. The maximal standardized uptake value (SUV) in the region of interest was used to assess FDG uptake. RESULTS: Disease activity and knee function improved in all patients after TKA. There was a significant decrease in the number of patients with swollen or tender joints involving the right wrist, right knee and left knee. The SUV of bilateral wrist joints decreased significantly 12 weeks after TKA, whereas the SUVs of other large joints were unchanged. CONCLUSION: TKA can improve not only ADL and knee function, but also the disease activity index in RA patients. However, TKA has limited effectiveness against synovitis of the joints not undergoing surgery.
28698947 The effect of cryotherapy on total antioxidative capacity in patients with active seroposi 2017 Sep Patients with rheumatoid arthritis (RA) have increased oxidative stress, decreased antioxidant levels, and impaired antioxidant capacity. Cold treatments are used to relieve joint inflammation and pain. Therefore, we measured the effect of cold treatments on the antioxidative capacity of RA patients with active disease. Sixty patients were randomized to (1) whole body cryotherapy at -110 °C, (2) whole body cryotherapy at -60 °C, or (3) local cryotherapy. Each treatment was given three times daily for 7 consecutive days in addition to the conventional rehabilitation. Blinded rheumatologist evaluated disease activity before the first and after the last cryotherapy. We collected plasma samples daily immediately before the first and after the second cryotherapy and measured total peroxyl radical trapping antioxidant capacity of plasma (TRAP), which reflects global combined antioxidant capacity of all individual antioxidants in plasma. Baseline morning TRAP levels (mean, 95% CI), adjusted for age, body mass index, disease activity, and dose of prednisolone, were 1244 (1098-1391) µM/l in the local cryotherapy, 1133 (1022-1245) µM/l in the cryotherapy at -60 °C, and 989 (895-1082) µM/l in the cryotherapy at -110 °C groups (p = 0.006). After the first treatment, there was a rise in 1-h TRAP of 14.2 (-4.2 to 32.6) µM/l, 16.1 (-7.4 to 39.6) µM/l, and 23.6 (4.1-43.2) µM/l, respectively. The increase was significant in the whole-body cryotherapy -110 °C group (p < 0.001) but not significant between the groups (p = 0.78). When analyzed for the whole week, the daily morning TRAP values differed significantly between the treatment groups (p = 0.021), but there was no significant change within each treatment group. Whole-body cryotherapy at -110 °C induced a short-term increase in TRAP during the first treatment session with but not during other treatment modalities. The effect was short and the cold treatments did not cause a significant oxidative stress or adaptation during 1 week.
29210204 Validation and reliability of the Timed Up and Go test for measuring objective functional 2018 Oct AIM: This study aimed to validate the Timed Up and Go test (TUG) for measuring objective functional impairment in patients with established rheumatoid arthritis (RA) based on a prospective observational cohort of RA patients undergoing joint surgery. METHODS: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI and other patient-reported outcomes, including European Quality of life scale (EQ-5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI ≤0.5), normal HAQ (HAQ-DI ≤0.25), and the absence of disability in each HAQ-DI category were also determined by age. RESULTS: A total of 435 patients were enrolled and analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ-DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising, walking, reach and activity). After adjusting for age and sex, mean TUG values were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4-10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were 7.2 sec (5.9-8.5) in young patients (≤61 years), 9.1 sec (7.6-10.5) in middle-aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (≥71 years). CONCLUSION: TUG was significantly associated with functional impairment and aging in patients with long-standing RA. Thus, TUG could be useful in setting treatment goals for joint surgery and rehabilitation in established RA patients.
28850021 Suppression of active, but not total MMP-3, is associated with treatment response in a pha 2018 Jan OBJECTIVE: Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a commonly measured biomarker in rheumatology. The aim was to investigate the association of activated MMP-3 (actMMP3) species with treatment response compared to cMMP-3. METHODS: The LITHE biomarker study (n=741) was a 1-year phase III, double-blind, placebo-controlled, parallel group study of TCZ in RA patients on stable methotrexate. cMMP-3 and actMMP-3 were assessed in fasting serum at baseline, week 4, 16, 24 and 52. Patients not achieving ACR20 remission at week 16 or 28 received rescue treatment (escapers). Spearman's correlation was analysed between biomarker baseline level or biomarker delta and clinical measures. Changes in biomarker levels were studied as a function of time and treatment. RESULTS: ActMMP-3 16-week change in treatment groups was predictive of 1-year radiographic progression; a small change in actMMP3 was equal to worsening radiographics. Baseline cMMP-3 was associated with 52-weeks' radiographic status and cMMP3 16-weeks' change was predictive of 1-year change in disease activity. ActMMP-3 was dose-dependently decreased by TCZ, and escapers decreased in actMMP-3 upon treatment. CONCLUSIONS: ActMMP-3 and cMMP-3 were found to be efficacy biomarkers of TCZ and actMMP-3 were able to differentiated doses. Moreover, the suppression of actMMP3, but not cMMP3 was associated with treatment response. This study illustrates that two biomarkers of the same protein may have different predictive capacities.
28782994 Serum miR-210 and miR-155 expression levels as novel biomarkers for rheumatoid arthritis d 2017 Oct BACKGROUND: MicroRNAs play a crucial role in the regulation of immune response. We hypothesised roles for serum miR-210 and miR-155 in the diagnosis of rheumatoid arthritis (RA) and relationships with the clinical and laboratory variables including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). METHODS: MiR-210 and miR-155 levels were identified by real-time polymerase chain reaction (PCR). TNF-α and IL-1β were measured by enzyme-linked immunosorbent assay and routine markers by standard techniques in 100 patients with RA and 100 individuals as healthy controls. Disease activity in the patients was assessed by DA-S28. RESULTS: MiR-210 was lower in RA compared to controls [median/IQR 0.96 (0.8-1.24) vs. 4 (1.28-3.93), p < 0.001]. miR-210 correlated inversely with clinical and laboratory variables including TNF-α and IL-1β (both r = -0.96, p < 0.001). MiR-155 expression was increased in RA compared to controls [median/IQR 6 (3.5-8.1) vs. 1.0 (0.95-1.6), p < 0.001] and correlated with TNF-α and IL-1β (both r = 0.94, p < 0.001). In multivariate analysis, miR-210 and miR-155 were both independent diagnostic markers for RA, and both were associated with RA disease activity. CONCLUSION: Serum miR-210 and miR-155 levels are independent diagnostic markers for RA, out-performing several routine indices and reflect disease activity. Thus, miR-210 and miR-155 might serve as non-invasive biomarkers for the diagnosis of RA.
29441893 Effect of genetic polymorphisms of azathioprine-metabolizing enzymes on response to rheuma 2017 Jan 10 Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. In a previous study of Japanese SLE patients under low-dose AZA therapy, the group with the 94C>A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. However, it is not yet clear how genotypes relate to responsiveness to RA treatment. The genotypes ITPA 94C>A, TPMT*3C, NUDT15 595C>T, GST-M1, GST-T1 and MRP4/ABCC4 2269G>A of Japanese patients with RA were determined. The relationship between these genotypes and response to AZA therapy was evaluated using the Disease Activity Score 28 (DAS28) and various medical data. Of the 22 patients 15 had the ITPA 94C/C genotype, 7 had the ITPA 94C/A genotype, none had the TPMT*3C mutation, 4 had the NUDT15 595C>T mutation, 8 had the GST-M1 and T1 null genotypes and 9 had the MRP4/ABCC4 2269G>A mutation. Changes in DAS28 at 6 months after baseline were similar in both ITPA genotype groups. However, the maintenance dose of AZA was significantly lower in the C/A group than in the C/C group (0.85±0.30 mg/kg/day vs. 1.2±0.46 mg/kg/day, respectively; p = 0.043). The ITPA 94C/A group showed the same response to RA treatment as the C/C group, but at a lower dose. This demonstrates that RA patients with the ITPA 94C>A mutation are more responsive to AZA.
28570437 Identification and Validation of Clinically Relevant Clusters of Severe Fatigue in Rheumat 2017 Nov/Dec OBJECTIVE: The considerable heterogeneity of rheumatoid arthritis (RA)-related fatigue is the greatest challenge to determining pathogenesis. The identification of homogenous subtypes of severe fatigue would inform the design and analysis of experiments seeking to characterize the likely numerous causal pathways that underpin the symptom. This study aimed to identify and validate such fatigue subtypes in patients with RA. METHODS: Data were obtained from patients recruited to the British Society for Rheumatology Biologics register for RA, as either receiving traditional disease-modifying antirheumatic drugs (DMARD cohort, n = 522) or commencing anti-tumor necrosis factor therapy (anti-TNF cohort, n = 3909). In those reporting severe fatigue (Short-Form 36 vitality ≤ 12.5), this cross-sectional analysis applied hierarchical clustering with weighted-average linkage identified clusters of pain, fatigue, mental health (all Short-Form 36), disability (Health Assessment Questionnaire), and inflammation (erythrocyte sedimentation rate) in the DMARD cohort. K-means clustering sought to validate the solution in the anti-TNF cohort. Clusters were characterized using a priori generated symptom definitions and between-cluster comparisons. RESULTS: Four severe fatigue clusters, labeled as basic (46%), affective (40%), inflammatory (4.5%), and global (8.9%) were identified in the DMARD cohort. All clusters had severe levels of pain and disability and were distinguished by the presence/absence of poor mental health and high inflammation. The same symptom clusters were present in the anti-TNF cohort, although the proportion of participants in each cluster differed (basic = 28.7%; affective = 30.2%; global = 24.1%; inflammatory = 16.9%). CONCLUSIONS: Among RA patients with severe fatigue, recruited to two diverse RA cohorts, clinically relevant clusters were identified and validated. These may provide the basis for future mechanistic studies and ultimately support a stratified approach to fatigue management.
24447879 Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in Alg 2017 Dec INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory and multifactorial disease. Genetic predisposition seems to play an important role. The aim of this study is to explore the relationship between human leukocyte antigen (HLA)-DRB1 alleles and susceptibility, clinical and biological features of RA in an Algerian patient population. METHODS: Using polymerase chain reaction - sequence specific primers (SSP), 134 RA patients and 132 healthy controls were genotyped for HLA-DRB1 and HLA-DRB1*04 subtypes. RESULTS: HLA-DRB1*04 was found to have increased frequency in the RA group compared to controls (P < 0.001, OR = 3.14), and was associated with anti-citrullinated protein antibodies positivity (ACPA) (P = 0.01, OR = 2.35). In contrast, HLA-DRB1*07 was found to have a decreased frequency in patients compared to controls (P = 0.003, OR = 0.44) and significant decrease was observed in patients with the rheumatoid factor (RF) positivity subgroup (P = 0.009, OR = 0.29). HLA-DRB1*04:05 was associated with RA (P = 0.005, OR = 3.41), whereas, HLA-DRB1*04:02 showed a protective effect against RA (P = 0.003, OR = 0.20). CONCLUSIONS: HLA-DRB1*04 was associated with increased risk for RA and ACPA positivity, while HLA-DRB1*07 was associated with reduced risk for RA and RF synthesis in Algerian patients.
28972432 Interleukin-34 Promotes Fibrocyte Proliferation. 2017 Oct Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting multiple joints. It remains unclear which factors in the circulation are associated with the systemic spread of the disease. Fibrocytes are pluripotent mesenchymal stem cells present in the circulation of RA patients. Our earlier findings implicated activated fibrocytes in the etiology of onset and pathogenesis of RA. Elevated levels of interleukin-34 (IL-34) in the serum and synovial fluid of RA patients are associated with rheumatoid factor and anticyclic citrullinated peptide antibodies, indicators of RA. Moreover, IL-34 levels are independent predictors of radiographic progression in RA patients. We provide evidence of simultaneous elevated levels of IL-34 and increased numbers of activated fibrocytes in the circulation of mice induced to develop arthritis. In vitro, IL-34 treatment induced the proliferation of fibrocytes, mediated by activation of cognate CSF-R1s on fibrocytes. Taken together, we infer that IL-34 has a role in stimulating fibrocyte proliferation and activation during arthritis, thereby contributing to both onset of RA and systemic spread of disease.
25990366 Ambulatory arterial stiffness index and carotid intima-media thickness in hypertensive rhe 2017 Dec AIM: Rheumatoid arthritis is associated with accelerated atherosclerosis. However, little is known about preclinical atherosclerosis in hypertensive rheumatoid arthritis patients. In this cross-sectional study we assessed the expression of preclinical atherosclerosis in hypertensive rheumatoid arthritis patients in comparison with matched hypertensive non-rheumatoid arthritis patients. METHODS: The study included 52 hypertensive rheumatoid arthritis patients and 42 hypertensive non-rheumatoid arthritis patients. The patients were extensively examined clinically and laboratory tested. The expression of preclinical atherosclerosis was estimated by assessing ambulatory arterial stiffness index and common carotid intima-media thickness. RESULTS: Arterial stiffness index and common carotid intima-media thickness were higher in hypertensive rheumatoid arthritis patients than in hypertensive non-rheumatoid arthritis patients. There was no correlation between arterial stiffness index and common carotid intima-media thickness with markers of inflammation and disease activity in hypertensive rheumatoid arthritis patients. CONCLUSION: The expression of subclinical atherosclerosis is more pronounced in hypertensive rheumatoid arthritis than in hypertensive non- rheumatoid arthritis patients.
28061896 Improving patient flow of people with rheumatoid arthritis has the potential to simultaneo 2017 Jan 7 BACKGROUND: In our current economic climate of scarce resources there is a lot of debate around the best - and most efficient - way of delivering care, which points patients towards the right physician at the earliest opportunity. The aim of the study was to assess whether an improvement in the interdisciplinary management of rheumatoid arthritis (RA) has the potential to simultaneously improve health outcomes and reduce costs. METHODS: In a first step, we modelled the ways which lead patients with RA to the correct diagnosis, and the relevant specialist, respectively. On average, a patient experiences 3 GP visits before referral to a specialist. We compared this situation against a reconfiguration of current practice towards a more proactive identification and referral method with initiation of care by a rheumatologist early in the disease. We evaluated the impact of this reconfiguration on the number of RA patients diagnosed and the costs associated with the diagnostic process. RESULT: Using data on epidemiology and Austrian practice patterns, we estimate a total of 5294 people with undifferentiated arthritis per year, of which 1765 suffer from RA. Modelling for diagnostic accuracy, we found that 1200 of these patients are initially misdiagnosed in a primary care setting and 95 at a rheumatologist. Our model found that a reconfiguration of current practice towards an approach of more integrated care has the potential to be not only cost-effective, but cost-saving: EUR 100,188 could be saved annually by exclusively adopting the new approach. CONCLUSIONS: Our results show that by better directing the flow of people with RA, simultaneous clinical and economic benefits may be reaped:.