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ID PMID Title PublicationDate abstract
31984422 The impact of long-term biologics/target therapy on bone mineral density in rheumatoid art 2020 Sep 1 OBJECTIVES: To investigate changes in BMD in RA patients receiving 3-year biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or conventional synthetic DMARD (csDMARD). METHODS: Patients with RA were recruited from September 2014 until March 2019. Clinical characteristics, BMD and evidence of fragility fractures at enrolment were documented. Participants were treated according to the National Institute for Health and Care Excellence (NICE) guidelines over a 3-year observation period. Repeated BMD was measured at the end of the study period. Participants were grouped into those receiving b/tsDMARD or csDMARD and by propensity score matching (1:2). RESULTS: A total of 388 participants completed the 3-year follow-up. After propensity score matching, 92 and 184 participants were allocated to the b/tsDMARD (Group I) and csDMARD (Group II), respectively. After 3 years, BMD remained stable at the femoral neck (FN), hip (total) (TH) and lumbar vertebra (L1-4) (P =0.09, 0.15, 0.87) in Group I. However, BMD decreased significantly in Group II (P=0.045, <0.001, 0.004) at corresponding sites. Participants receiving combined b/tsDMARD and anti-osteoporosis therapy experienced a greater BMD preserving effect than other subgroups. CONCLUSION: Long-term b/tsDMARDs therapy had protective effects on bone loss for patients with RA. Patients receiving concomitant anti-osteoporosis therapy and b/tsDMARDs therapy experienced the greatest BMD preserving effect.
31662320 Shared decision making in routine clinical care of patients with rheumatoid arthritis: an 2020 Feb OBJECTIVES: Although shared decision making (SDM) is advocated in rheumatoid arthritis (RA) treatment, it is largely unclear when, how and to what extent SDM is applied in routine clinical care of patients with RA. This study aimed to investigate the level of SDM in RA treatment from an observer perspective and to assess associations between the level of SDM and characteristics of the clinician, patient and consultation. METHODS: The level of SDM was investigated by scoring audio-recordings of 168 routine consultations with unique patients with the observer patient involvement (OPTION) scale (scale 0-100, higher OPTION scores indicating higher levels of SDM). Associations between the level of SDM and characteristics of the clinician, patient and consultation were assessed using multilevel modelling. Statistical significance was set at p<0.05. RESULTS: The mean OPTION score was 28.3 (SD=15.1). The multilevel model included four characteristics: clinician age, patient age, consultation duration and type of treatment decision. There were significant, positive associations between the level of SDM and the consultation duration (b=0.63, 95% CI 0.16 to 1.11), decision for stopping and/or starting medication (b=14.30, 95% CI 5.62 to 22.98), decision for adjusting medication doses (b=8.36, 95% CI 3.92 to 12.81) and decision for administering single dose glucocorticoids (b=15.03, 95% CI 9.12 to 20.93). Thus, a higher level of SDM was significantly associated with a longer consultation duration and the type of treatment decision. No other significant associations were found. CONCLUSIONS: Overall, the level of SDM in RA treatment leaves room for improvement. To foster SDM in routine clinical care, training programmes on patient-centred communication skills may be helpful.
32656986 Repeat serological testing for anti-citrullinated peptide antibody after commencement of t 2020 Jul AIM: To Investigate the prevalence of seroconversion to ACPA after commencement of triple disease-modifying anti-rheumatic drug (DMARD) treat-to-target therapy. BACKGROUND: Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) define 'seropositive' rheumatoid arthritis (RA). Both predict unfavourable disease course, development of extra-articular features and treatment outcomes. We investigated the prevalence of seroconversion to ACPA after commencement of triple disease-modifying anti-rheumatic drug (DMARD) treat-to-target therapy. METHODS: DMARD-naïve patients with RA according to the 1987 American College of Rheumatology criteria and disease duration of <96 weeks were enrolled. RF and ACPA levels were recorded at baseline and sequentially during triple DMARD therapy. RESULTS: A total of 368 patients were followed for a median of 272 weeks. Of 154 patients seronegative for ACPA at recruitment, 10 (6.5%) seroconverted at some point. Nine of these were positive for RF at baseline and baseline RF titre was predictive of seroconversion. Four (2.6%) patients remained seropositive. No patients seroconverted from negative to positive for both RF and ACPA. Median time to seroconversion for ACPA was 29 months. CONCLUSION: Persistent seroconversion of ACPA from negative to positive after diagnosis in patients with RA is uncommon. ACPA and RF double negative patients are highly unlikely to ever develop ACPA positivity with a risk <1%. It is therefore unlikely to be helpful or cost effective to perform serial ACPA measurements in patients with seronegative RA after commencement of a treat-to-target strategy.
31782789 Smoking cessation is associated with lower disease activity and predicts cardiovascular ri 2020 Aug 1 OBJECTIVES: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. METHODS: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. RESULTS: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. CONCLUSION: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.
31918120 Preliminary study of the association of serum irisin levels with poor sleep quality in rhe 2020 Mar STUDY OBJECTIVES: Sleep disorders are significant problems in patients with rheumatoid arthritis (RA) and are associated with poor quality of life. Irisin is myokine which may have anti-inflammatory and energy regulatory roles. This study assessed the association of serum irisin levels with the quality of sleep and disease activity in RA patients. METHODS: In sum, 58 RA patients and 30 matched healthy controls were included. Disease activity score in 28 joints (DAS28-ESR) and the patients' global score were calculated. RA patients were grouped according to the Pittsburgh Sleep Quality Index score (PSQI) into good-sleepers (group 1) defined as a PQSI score≤5 and poor sleepers (group 2) with a PSQI > 5. Serum irisin levels were measured for both patients and controls by commercially available enzyme-linked immunosorbent assay kits. RESULTS: Poor sleep quality was found in 26 (45%) of the RA patients. Irisin levels were significantly lower in RA patients with poor sleep compared to those with good sleep and healthy controls (p < 0.001). Serum irisin levels correlated inversely with disease duration, morning stiffness duration, DAS28-ESR, global score, and total PSQI score (r = -0.722 to -0.263 & p values≤0.001-0.04) indicating a possible anti-inflammatory role of irisin in RA patients. The analysis employed Student's t-test, ANOVA, and Pearson correlation. CONCLUSIONS: Irisin levels were decreased in RA patients with poor sleep quality compared to RA patients with good sleep quality and healthy controls, indicating a possible association of decreased serum irisin with sleep impairment in RA patients.
33331311 [Clinical characteristics and risk factors of cardiovascular disease in patients with elde 2020 Dec 18 OBJECTIVE: To investigate the clinical characteristics of patients with elderly-onset rheumatoid arthritis (EORA), and the risk factors of EORA complicated with cardiovascular disease (CVD). METHODS: A cross-sectional study was conducted in Peking University People's Hospital from July 2009 to December 2014 and 1 116 patients were recruited. The patients' characteristics and CVD, including ischemic heart disease, cerebral and peripheral vascular disease, were recorded. The patients were divided into EORA group (n=212) and younger-onset rheumatoid arthritis (YORA) group (n=904) according to the age of onset ≥60 years and < 60 years. Then, the differences between the groups were analyzed by Student's t test, Mann-Whitney U test or χ(2)test, and risk influencing CVD were analyzed using Logistic regression. RESULTS: There was no significant difference in the disease activity between the EORA and YORA groups. The proportion of male, pulmonary interstitial disease (ILD), and numbers of deformity joint count (DJC) were significantly higher in the EORA group compared with the YORA group [32.1% vs. 18.5%, χ(2)=19.11, P < 0.001; 23.6% vs. 13.6%, χ(2)=16.50, P < 0.001; 6 (2, 12) vs. 3 (2, 7), Z=-3.60, P < 0.001], while the prevalence of Sjögren's syndrome was lower than that of the YORA group (13.5% vs. 5.2%, χ(2)=11.29, P=0.001). Moreover, there were lower prevalences in the patients treated with disease-modifying antirheumatic drugs (DMARDs) in EORA group (35.4%) than in YORA group (26.7%) (χ(2)=6.43, P=0.011), especially in methotrexate (MTX), hydroxychloroquine (HCQ) and sulfasalazine (SSZ). In addition, the patients with EORA had a higher prevalence of CVD (27.8%) than the YORA group (11.6%, χ(2)=40.46, P < 0.001), accompanied with higher prevalence of smoking, hypertension, and hyperlipidemia. Multivariate Logistic regression analysis showed that elder age (OR=1.10, 95%CI: 1.00-1.20), DJC (OR=3.17, 95%CI: 1.04-9.68), rheumatoid nodules (OR=3.56, 95%CI: 1.03-12.23), hypertension (OR=2.37, 95%CI: 1.09-5.13) and hyperlipidemia (OR=8.85, 95%CI: 2.50-31.27) were independent risk factors, while HCQ (OR=0.22, 95%CI: 0.07-0.70) and MTX (OR=0.32, 95%CI: 0.14-0.73) were protective factors of EORA complicated with CVD. CONCLUSION: Compared with YORA, patients with EORA have higher ratio of male, ILD and DJC, which may be attributed to inappropriate therapies. EORA is more likely to be complicated with CVD than YORA. Elder age, DJC, rheumatoid nodules, hypertension, and hyperlipidemia are independent risk factors, while HCQ and MTX are protective factors of EORA complicated with CVD.
32191279 RNA-seq reveals the circular RNA and miRNA expression profile of peripheral blood mononucl 2020 Apr 30 OBJECTIVE: Circular RNAs (circRNAs) are a significant class of molecules involved in a wide range of diverse biological functions that are abnormally expressed in many types of diseases. The present study aimed to determine the circRNAs specifically expressed in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify their possible molecular mechanisms. METHODS: To identify the circRNAs specifically expressed in RA, we started by sequencing the of PBMCs circRNA and microRNAs (miRNAs) from a RA group (n = 3) and a control group (n = 3). We constructed a network of differentially expressed circRNAs and miRNAs. Then, we selected differentially expressed circRNAs in PBMCs from 10 RA patients relative to 10 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Spearman's correlation test was used to evaluate the correlation of circRNAs with biochemical measurements. RESULTS: A total of 165 circRNAs and 63 miRNAs were differently expressed between RA patients and healthy people according to RNA-seq, including 109 circRNAs that were significantly up-regulated and 56 circRNAs that were down-regulated among the RA patients. RT-qPCR validation demonstrated that the expression levels of hsa_circ_0001200, hsa_circ_0001566, hsa_circ_0003972, and hsa_circ_0008360 were consistent with the results from the sequencing analysis. Then, we found that there were significant correlations between the circRNAs and disease severity. CONCLUSION: Generally, these results suggest that expression of hsa_circ_0001200, hsa_circ_0001566, hsa_circ_0003972, and hsa_circ_0008360 in PBMCs from RA patients may serve as potential biomarkers for the diagnosis of RA, and these circRNAs may influence the occurrence and development of RA.
32691642 Extent of atherosclerosis after 11-year prospective follow-up in patients with early rheum 2020 Nov Objective: Cardiovascular disease (CVD) is increased among patients with rheumatoid arthritis (RA). The underlying cause is not clear. In this prospective study, patients with early RA were investigated for associations between subclinical atherosclerosis and CVD risk factors as well as inflammation. Method: At diagnosis, RA patients were recruited into a prospective study. A subgroup was included (n = 55) for ultrasound measurements of intima-media thickness (IMT) at inclusion (T0), and after 5 years (T5) and 11 years (T11). Thirty-one age and gender-matched controls were also included for comparison. Results: IMT increased significantly between T0 and T11 among patients and controls (p < 0.0001). No statistically significant differences in IMT between patients and controls were detected at T11, T5, or T0 (p > 0.05 for all). In simple regression models, IMT at T11 was significantly associated with age (p < 0.0001), as well as systolic blood pressure at T0 (p < 0.01) and T11 (p < 0.01) among RA patients. Furthermore, the composite Systematic COronary Risk Evaluation (SCORE) measurements (p < 0.0001) and Reynolds risk score (p < 0.01) and the radiographic Larsen score (p < 0.05) at T0 were all significantly associated with IMT at T11. Results from conditional logistic regression analysis showed an increased progression rate between T0 and T11 in the RA group compared with controls (p < 0.05). Conclusion: We found increased atherosclerotic development among patients with RA compared with controls 11 years after diagnosis. The atherosclerotic burden was associated with disease severity at baseline.
33146469 Anti-carbamylated protein and peptide antibodies as potential inflammatory joint biomarker 2020 Dec OBJECTIVE: Antibodies against carbamylated proteins/peptide (CarP) have been associated with severity in rheumatoid arthritis (RA) patients. However, their role in risk groups, specific targets and relation with periodontal disease (PD) is uncertain yet. The aim of this study was evaluated the association between the levels of anti-CarP with clinical manifestation, human leukocyte antigen (HLA) alleles, periodontal activity markers, PD diagnosis, PD severity, and presence of Porphyromonas gingivalis (P gingivalis) in relatives of patients with RA. METHODS: One hundred and twenty-four individuals with a family history of RA in first-degree relatives (FDR) and 124 healthy individuals gender- and age-matched, RA activity was assessed. Antibodies against carbamylated protein anti-FCS-Carp and 2 carbamylated peptides of fibrinogen were selected (anti-Ca-Fib2, anti-Ca-Fib3). RESULTS: Anti-FCS-Carp-positive, anti-Ca-Fib2 and anti-Ca-Fib3 were more frequent in FDR than controls (25.0% vs 14.5%, 34.7% vs 15.3% and 33.1% vs 11.3%, respectively). Anti-FCS-CarP were associated with the HLA-DRB1-SE* 1402 allele (P = .035) and highly sensitive C-reactive protein levels (P = .016), the anti-Ca-Fib2 antibodies were associated with the HLA-DRB1-SE* 1501 allele (P = .03), with non-SE* 0901 allele (P = .01), the anti-Ca-Fib3 was associated with positive rheumatoid factor (P = .0012). The FDR condition was associated with the presence of anti-Ca-Fib3 (odds ratio [OR] =4.7; 95% CI = 1.8-11.7; P = .001) and painful joints (OR = 2.2; 95% CI = 1.01-4.68; P = .045); we also detected an important trend toward the presence of P gingivalis (OR = 1.9; 95% CI = 0.9-3.7; P = .062). CONCLUSION: The presence of anti-FCS-Carp, anti-Ca-Fib3 and anti-Ca-Fib2 antibodies may have a role for these antibodies as early biomarkers in the development of RA, probably including additional mechanisms related with other non-SE alleles; the anti-peptide antibodies proposed in the present study may represent a simpler way to identify antibodies directed to a specific target.
31930319 Comparison of methods to construct a genetic risk score for prediction of rheumatoid arthr 2020 Jul 1 OBJECTIVES: To evaluate selection methods among published single-nucleotide polymorphisms (SNPs) associated with RA to construct predictive genetic risk scores (GRSs) in a population-based setting. METHODS: The Nord-Trøndelag Health (HUNT) Study is a prospective cohort study among the whole adult population of northern Trøndelag, Norway. Participants in HUNT2 (1995-1997) and HUNT3 (2006-2008) were included (489 RA cases, 61 584 controls). The initial SNP selection from relevant genome-wide studies included 269 SNPs from 30 studies. Following different selection criteria, SNPs were weighted by published odds ratios. The sum of each person's carriage of all weighted susceptibility variants was calculated for each GRS. RESULTS: The best-fitting risk score included 27 SNPs [weighted genetic risk score 27 (wGRS27)] and was identified using P-value selection criterion ≤5 × 10-8, the largest possible SNP selection without high linkage disequilibrium (r2 < 0.8), and lasso regression to select for positive coefficients. In a logistic regression model adjusted for gender, age and ever smoking, wGRS27 was associated with RA [odds ratio 1.86 (95% CI 1.71, 2.04) for each s.d. increase, P < 0.001]. The AUC was 0.76 (95% CI 0.74, 0.78). The positive and negative predictive values were 1.6% and 99.7%, respectively, and the positive predictive value was not improved in sensitivity analyses subselecting participants to illustrate settings with increased RA prevalences. Other schemes selected more SNPs but resulted in GRSs with lower predictive ability. CONCLUSION: Constructing a wGRS based on a smaller selection of informative SNPs improved predictive ability. Even with a relatively high AUC, the low PPV illustrates that there was a large overlap in risk variants among RA patients and controls, precluding clinical usefulness.
31116056 Age and female gender associated with periodontal disease in Japanese patients with rheuma 2020 May Objectives: This study aimed to evaluate the prevalence of, and the factors associated with, periodontal disease in Japanese patients with rheumatoid arthritis (RA).Methods: Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed three self-administered questionnaires including questions about recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and any history of periodontitis. Logistic regression analyses were used to evaluate associations with clinical variables for each questionnaire.Results: Among 5600 Japanese patients with RA, 31.0%, 18.3%, and 20.4% of patients self-reported recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and a history of periodontitis, respectively. In multivariate models, younger age, fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), and prednisolone dosage were significantly (p < .05) associated with recent gingival bleeding during toothbrushing. Older age, female gender, and ever-smoker status were significantly correlated with a recent diagnosis of periodontitis.Conclusion: Many Japanese patients with RA experience gingival bleeding during toothbrushing and are diagnosed with periodontitis. Age, female gender, ever-smoker status, fracture history, JHAQ-DI, and prednisolone dosage appeared to be associated with periodontal disease in Japanese patients with RA.
30285533 Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese pat 2020 Jan Objectives: To confirm the safety and effectiveness of high-dose (>8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan.Methods: A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for 24 or 52 weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted.Results: The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24 and 52-week follow-up groups, respectively. Incidence of adverse drug reactions (ADRs) and serious ADRs was 21.42 and 1.66% in the 24-week and 35.52 and 2.69% in the 52-week groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-week (4.09-3.21) and 52-week treatment (3.91-2.80; both p < .001). In a majority of patients at baseline who had high-to-moderate disease activity, the remission rate (defined as DAS28-4ESR <2.6) increased three-fold from 10.6% (baseline) to 33.0% (24-week) compared to patients with low disease activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6% (24 weeks).Conclusion: High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.
32569434 lncRNA expression profiles related to apoptosis and autophagy in peripheral blood mononucl 2020 Aug Long noncoding RNAs (lncRNAs) are >200-bp molecules that do not generally code for proteins. Human lncRNAs have well-characterized roles in gene expression regulation, particularly with regard to protein-coding genes, and their dysregulation has been linked to disease. Here, we set out to investigate changes in the expression of lncRNAs related to apoptosis and autophagy in the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA). In addition, we aimed to correlate lncRNA expression profiles with clinical indexes and self-perception of patients (SPP). To this end, we employed RNA sequencing of lncRNAs in PBMCs from three patients with RA and three healthy controls. We used bioinformatics to screen several dysregulated lncRNAs related to apoptosis and autophagy. To validate key lncRNA candidates, we performed quantitative reverse transcriptase-PCR on 20 patients with RA and 20 healthy controls. We found the expression of seven lncRNAs (MAPKAPK5-AS1, ENST00000619282, C5orf17, LINC01189, LINC01006, DSCR9 and MIR22HG) was significantly altered in PBMCs of patients with RA. Receiver operating characteristic curve analysis suggested that MIR22HG [area under the curve (AUC) = 0.846, P = 0.000], DSCR9 (AUC = 0.783, P = 0.005), LINC01189 (AUC = 0.677, P = 0.034), MAPKAPK5-AS1 (AUC = 0.644, P = 0.025) and ENST00000619282 (AUC = 0.636, P = 0.043) are potential biomarkers of RA. Spearman's correlation analysis revealed selected lncRNAs correlated with clinical indexes and SPP. Therefore, we highlight that some lncRNAs related to apoptosis and autophagy may serve as potential biomarkers for diagnosis and monitoring of RA progression, which also correlate with several clinical indexes and SPP.
31729609 Physical exercise and low-level laser therapy on the nociception and leukocyte migration o 2020 Aug Rheumatoid arthritis denotes hyperplasia and intense inflammatory process. Treatment involves exercise protocols and use of resources such as low-level laser therapy (LLLT) to modulate the inflammatory process and maintain physical capacity. The objective was to investigate whether treatment with LLLT and exercise modulates the inflammatory process and peripheral functionality. Sample is composed of 128 male rats, separated into three groups, control, treated and untreated, in the acute and chronic period of the disease with 64 animals in each group, divided into 8 subgroups with n = 8. The animals were immunized with injection at the base of the tail and 7 days after intra-articular injection with complete Freund adjuvant (CFA) for lesion groups, and saline solution for the controls. Joint disability was evaluated by PET (paw elevation time) and joint edema and treated with LLLT and/or resisted stair climbing exercise. Normality Shapiro-Wilk test, ANOVA mixed for the functional analyses, and ANOVA one-way for the variables of cellular differentiation, with Bonferroni post hoc, p = 5% were used. For the evaluations of joint disability and nociception, there was a significant difference between the evaluations, the groups, and the interaction groups-evaluations. The treated groups showed recovery of functionality; it is still verified that laser therapy increased the nociceptive threshold of the chronic inflammatory period, and the exercise reflected in significant functional improvement and modulation of the inflammatory process both in the acute and chronic periods. LLLT, resistance exercise, or a combination of treatments had a positive effect on the modulation of the inflammatory process, reducing the migration of leukocytes, in addition to helping the return of peripheral functionality by reducing joint disability in a model of rheumatoid arthritis induced by CFA in rats.
31486066 Integrative analysis of genome-wide association study and expression quantitative trait lo 2020 Jan Rheumatoid arthritis (RA) is an autoimmune chronic disorder manifesting as warm, swollen, and painful joints. Multiple immune cells are implicated in the development of RA. Previous studies demonstrated that integrating the genetic information of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) is capable of identifying new disease-risk loci and providing novel insights into the etiology of complex human disease. In this study, we conducted an integrative pathway association analysis of RA by using GWAS summary data and five immune cell types related to eQTL datasets of RA. After combining the cell-specific eQTLs and GWAS summary of RA and performing a pathway-enrichment analysis, we detected a group of RA-associated pathways with common or cell-specific enriched in the five immune cell types. 41 pathways for B cells, 33 pathways for CD4(+) T cells, 27 pathways for CD8(+) T cells, 39 pathways for monocyte, and 25 pathways for natural killer cells are significant in RA, among which 48% are common pathways and 32% are cell-specific pathways. We detected a group of RA-associated eQTL pathways related to five different immune cell types. Our findings may provide novel insights into the pathogenesis of RA.
31483182 Validity and responsiveness of the Work Functioning Impairment Scale (WFun) in rheumatoid 2020 Sep Objective: Previous studies have not fully evaluated the measurement properties of the Work Functioning Impairment Scale (WFun) in clinical situations and there are no data from patients with rheumatoid arthritis (RA). This study aimed to investigate the convergent validity and responsiveness of the WFun in patients with RA.Methods: This substudy was a part of the multicenter, observational, prospective FIRST ACT-SC study. In total, 322 paid workers with RA received anti-rheumatic drugs at baseline. The WFun, Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Work Productivity and Activity Impairment Questionnaire (WPAI), and Japanese Health Assessment Questionnaire Disability Index (HAQ-DI) were administrated at baseline and weeks 12, 24, and 52. Multilevel regression analyses were performed.Results: High average WFun scores were associated with higher score categories of the DAS28-ESR, CDAI, SDAI, WPAI and HAQ-DI. Average WFun change scores linearly decreased with decreases on each instruments.Conclusion: The findings indicate that the WFun has reasonable measurement properties: the scale demonstrated validity and responsiveness with RA patients. The WFun could be useful in assessing presenteeism in patients with RA.
31378115 Plasma levels of the soluble form of the FcγRIIa receptor vary with receptor polymorphism 2020 Soluble forms of the low-affinity immunoglobulin receptor FcγRIIa (sFcγRIIa) lacking the cytoplasmic tail have been reported in plasma however the mechanism and functional consequences are unknown. This study aimed to evaluate mechanisms of FcγRIIa release compared to GPVI release from platelets, and examine whether genetic polymorphisms at positions 27 and 131 within FcγRIIa correlate with platelet FcγRIIa stability and function. Enzyme-linked immunosorbent assays (ELISAs) were used to measure plasma sFcγRIIa and sGPVI levels. FcγRIIa genotype at positions 27 and 131 was evaluated. sFcγRIIa levels were not significantly different between non-131HH and 131HH but were significantly lower in 27W than non-27W. Treatment of platelets with aggregated immunoglobulin (Ig) G induced release of FcγRIIa and GPVI, but only sGPVI release was statistically significant, required functional FcγRIIa, and was blocked by inhibitors of signaling pathways and metalloproteinases. This indicated that sFcγRIIa was not released from platelets by metalloproteolysis. sFcγRIIa levels were not correlated with sGPVI levels in healthy individuals however levels of sFcγRIIa and sGPVI in plasma from patients with rheumatoid arthritis (RA) were significantly elevated above levels found in healthy individuals. Elevated level of sFcγRIIa in RA patients may reflect active immune-based arthritis and be predictive of active inflammation.
32221385 Convolutional neural network for classification of two-dimensional array images generated 2020 Mar 27 This research aimed to study the application of deep learning to the diagnosis of rheumatoid arthritis (RA). Definite criteria or direct markers for diagnosing RA are lacking. Rheumatologists diagnose RA according to an integrated assessment based on scientific evidence and clinical experience. Our novel idea was to convert various clinical information from patients into simple two-dimensional images and then use them to fine-tune a convolutional neural network (CNN) to classify RA or nonRA. We semi-quantitatively converted each type of clinical information to four coloured square images and arranged them as one image for each patient. One rheumatologist modified each patient's clinical information to increase learning data. In total, 1037 images (252 RA, 785 nonRA) were used to fine-tune a pretrained CNN with transfer learning. For clinical data (10 RA, 40 nonRA), which were independent of the learning data and were used as testing data, we compared the classification ability of the fine-tuned CNN with that of three expert rheumatologists. Our simple system could potentially support RA diagnosis and therefore might be useful for screening RA in both specialised hospitals and general clinics. This study paves the way to enabling deep learning in the diagnosis of RA.
31999341 Conventional versus ultrasound treat to target: no difference in magnetic resonance imagin 2020 Sep 1 OBJECTIVE: To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. METHODS: A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. RESULTS: MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. CONCLUSION: Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.
33325525 Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthri 2020 Dec 23 BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases. The present study aimed to identify hub genes involved in the pathogenesis and further explore the potential treatment targets of RA and OA. METHODS: The gene expression profile of GSE12021 was downloaded from Gene Expression Omnibus (GEO). Total 31 samples (12 RA, 10 OA and 9 NC samples) were used. The differentially expressed genes (DEGs) in RA versus NC, OA versus NC and RA versus OA groups were screened using limma package. We also verified the DEGs in GSE55235 and GSE100786. Functional annotation and protein-protein interaction (PPI) network construction of OA- and RA-specific DEGs were performed. Finally, the candidate small molecules as potential drugs to treat RA and OA were predicted in CMap database. RESULTS: 165 up-regulated and 163 down-regulated DEGs between RA and NC samples, 73 up-regulated and 293 down-regulated DEGs between OA and NC samples, 92 up-regulated and 98 down-regulated DEGs between RA and OA samples were identified. Immune response and TNF signaling pathway were significantly enriched pathways for RA- and OA-specific DEGs, respectively. The hub genes were mainly associated with 'Primary immunodeficiency' (RA vs. NC group), 'Ribosome' (OA vs. NC group), and 'Chemokine signaling pathway' (RA vs. OA group). Arecoline and Cefamandole were the most promising small molecule to reverse the RA and OA gene expression. CONCLUSION: Our findings suggest new insights into the underlying pathogenesis of RA and OA, which may improve the diagnosis and treatment of these intractable chronic diseases.