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ID PMID Title PublicationDate abstract
35633522 Predictors of progression in rheumatoid arthritis-associated interstitial lung disease: A 2022 May 28 AIM: Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and is associated with high mortality, especially in progressive ILD. We aimed to identify predictors of disease progression in the early stages of ILD in a large sample of patients with RA. METHOD: The medical records of 201 RA-ILD patients were retrospectively analyzed. According to changes in their pulmonary function tests, patients were divided into progressive disease and stable disease groups. Data were collected on clinical characteristics, laboratory findings, chest high-resolution computed tomography, and therapeutic agents. Univariate and multivariate analyses were performed to identify predictors of ILD progression. RESULTS: During a median follow up of 38 months, 105 (52.5%) patients were diagnosed with progressive ILD. These patients were mostly male, past or present smokers (P = 0.028, P = 0.021, respectively). Higher Health Assessment Questionnaire-Disability Index score and higher Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) were observed in the ILD progression group (P = 0.003, P < 0.001, respectively). There were no significant differences in baseline respiratory symptoms, pulmonary function, or laboratory features. Multivariate analysis indicated that high DAS28-ESR, definite usual interstitial pneumonia pattern, fibrosis score, and less use of cyclophosphamide were independent risk factors for RA-ILD progression. Fifteen (7.46%) patients died during the follow up, and the most frequent cause of death was lung infection. CONCLUSION: Our results suggested that high disease activity, definite usual interstitial pneumonia pattern, fibrosis score, and less use of cyclophosphamide at the onset of ILD may indicate the progression of ILD in RA patients.
35492365 The Infection, Coinfection, and Abundance of Intestinal Protozoa Increase the Serum Levels 2022 Protozoa, nematodes, and platyhelminths are of clinical interest due to their role on the modulation of the immune responses. To determine the frequency of infection by intestinal parasites as well as the status of single or mixed infection (coinfection) and its relation with inflammation and intestinal permeability markers in patients with rheumatoid arthritis (RA), a cross-sectional study was conducted in 18 women diagnosed with RA. A fecal sample of each participant was analyzed for parasitic identification. The DAS28-erythrocyte sedimentation rate score, as well as the serum levels of TNF-α, IL-10, IL-17A, and the intestinal fatty-acid binding protein 2 (IFABP2), was determined through the ELISA technique. The T CD4+ and CD8+ lymphocytes' proportions were determined by flow cytometry. In this study, 50% (n = 9) of the total sample tested were positive to the presence of intestinal protozoa (27% by single infection and 22.2% by coinfection). Blastocystis sp. and Endolimax nana were the most frequently identified protozoa. The serum levels of IFABP2 were increased in patients with infection by protozoa, mainly in those individuals with coinfection and a larger abundance of Blastocystis sp. We found that coinfection by protozoa was related to higher levels of TNF-α and higher frequency of T CD4+ lymphocytes, mainly in patients under antirheumatic treatment. Infection by intestinal protozoa is associated with increased intestinal permeability in patients with RA; thus, infection, coinfection, and abundance of intestinal protozoa should be clinically screened because they could be an associated factor to the clinical variability of the disease.
35223954 Caffeine, Coffee, Tea and Risk of Rheumatoid Arthritis: Systematic Review and Dose-Respons 2022 OBJECTIVE: Prospective cohort studies on coffee, tea and caffeine in relation to the risk of rheumatoid arthritis (RA) have shown conflicting results. The aim of this study was to conduct a dose-response meta-analysis of cohort studies on the association between dietary caffeine, different types of coffee and tea consumption and the risk of RA. METHODS: PubMed/Medline, Scopus and EMBASE were searched up to July 2021 to identify relevant studies that had considered different types of coffee (caffeinated or decaffeinated), tea or caffeine exposure with RA as the main, or one of the, outcome(s). Two authors independently screened 742 publications. Finally, five prospective cohort studies were included in our meta-analysis. Pooled relative risks (RRs) were calculated by using a fixed-effects model. We also performed linear and non-linear dose-response analyses to examine the dose-response relations. RESULTS: Comparing extreme categories, we found a positive, significant association between coffee (RR: 1.30; 95% CI: 1.04-1.62; I (2) = 0%, n = 5) and decaffeinated coffee (RR: 1.89; 95% CI: 1.35-2.65; I (2) = 38.1%, n =3) consumption and risk of RA. One additional cup of coffee consumed per day was associated with an increased risk of RA by 6% (95% CI: 1.02-1.10; I (2) = 0%). This increase in the risk of RA for one cup/d of decaffeinated coffee was 11% (95% CI: 1.05-1.18; I (2) = 38). No significant association was observed between caffeinated coffee, tea or caffeine intake and the risk of RA. CONCLUSION: We found that a higher intake of coffee and decaffeinated coffee was associated with increased risk of RA. No significant association between caffeinated coffee, tea or caffeine intake and the risk of RA was observed. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227665, identifier: CRD42021227665.
35482485 Patient experienced symptom state in rheumatoid arthritis: sensitivity to change in diseas 2022 Apr 28 OBJECTIVES: The Patient Experienced Symptom State (PESS) is a single-question, patient-reported outcome which is validated to assess global disease impact in rheumatoid arthritis (RA). This study addresses its sensitivity to change and reliability. METHODS: Disease activity, disease impact in the 7 domains of RAID and PESS were assessed in patients with RA from the NOR-DMARD registry, at two visits, six-months apart. The PESS over the last week was scored in five levels, from "very bad" to "very good".Disease impact and disease activity were compared between patients who improved, maintained or worsened PESS over time, through one-way analysis of variance (ANOVA), with post-hoc Bonferroni correction. Correlations between changes in these parameters were assessed through Spearmańs correlation coefficient. Sensitivity to change was assessed by standardized response mean (SRM) between the two visits. Reliability was analyzed through intraclass correlation coefficient between the two visits in patients with stable disease activity and impact. RESULTS: In 353 patients (76.8% females, 9.9(9.6) years disease duration), patients who improved their PESS level was associated with substantial improvements in mean impact in all domains as well as disease activity. (p< 0.02). PESS change was moderately to strongly correlated with RAID domains and disease activity (rho: 0.4-0.7). PESS was responsive to change (SRM : 0.65, 95%CI: 0.54-0.76), particularly among RAID responders (SRM : 1.79, 95%CI: 1.54-1.99). PESS was moderately reliable in patients with stable condition (ICC: 0.72, 95%CI: 0.52-0.83). CONCLUSION: PESS is valid, feasible, reliable and responsive, representing an opportunity to improve the assessment of disease impact with minimal questionnaire burden.
35640491 Nanoparticulate DNA scavenger loading methotrexate targets articular inflammation to enhan 2022 May 24 Abnormal high cell-free DNA (cfDNA) activates toll-like receptor 9 (TLR9) in immune cell's endosome to produce inflammatory cytokines that aggravate rheumatoid arthritis (RA). Previously, we successfully developed cationic nanoparticles (cNPs) relieving symptoms of RA rats by scavenging cfDNA, but the strong positive charges of cNPs may cause systemic toxicity during circulation via intravenous injection. Herein, we design cNP-pp-PEG to shield the nanoparticles with MMP2-sensitive peptide (pp) linked PEG, the cations are exposed only when PEG is removed by MMP2, which is enriched in the inflamed articular cavity. Taking advantage of the self-assembled cNP-pp-PEG, hydrophobic methotrexate (MTX) is loaded into its core through hydrophobicity interaction, obtaining MTX@cNP-pp-PEG. The engineered reagents exhibit lower toxicity, longer retention time and higher accumulation in inflamed joints comparing to its counterpart MTX@cNP-pp due to the hidden cationic charges. Moreover, the anti-inflamed activity of MTX strengthens the therapeutic efficiency of cNPs. The dual roles of cNPs as therapeutic agent and MTX carrier significantly enhance the therapeutic efficacy and extended administration interval to 4 days. This research addresses the issues of targeting inflamed joints, reducing the systemic toxicities of both cNPs and MTX, and extending administration interval, demonstrating an upgraded strategy for DNA scavenger application.
35267027 Post hoc Analysis of Clinical Characteristics of Patients with Radiographic Progression in 2022 Mar 10 OBJECTIVE: To determine efficacy of peficitinib in reducing joint damage, and predictive factors affecting treatment response in Japanese patients with rheumatoid arthritis (RA). METHODS: This post hoc analysis used data from a placebo-controlled, phase 3 trial (RAJ4) of peficitinib in patients with RA and inadequate response to methotrexate. Erosion and joint space narrowing (JSN) was assessed at baseline and at Week 28/early termination (ET) of treatment using the van der Heijde-modified Sharp method. Univariate logistic regression analysis of change from baseline in modified total Sharp score identified predictive factors with significant treatment interaction; the effects of these factors on treatment response were further evaluated using a multivariate model. RESULTS: The analyses included 481 patients. For most joint groups, peficitinib demonstrated reduced change from baseline at Week 28/ET in erosion and JSN scores versus placebo; a numerically greater effect was observed with peficitinib 150mg versus 100mg. Baseline C-reactive protein (CRP) and prednisolone dose were identified as clinically significant negative predictive factors: treatment effect decreased as CRP or prednisolone dose increased, for both peficitinib doses. CONCLUSIONS: : Peficitinib 100mg and 150mg reduced joint damage versus placebo, across almost all joint groups. Higher baseline CRP and/or prednisolone dose were associated with reduced peficitinib efficacy. CLINICALTRIALS.GOV IDENTIFIER: : NCT02305849.
35069567 Innate Lymphoid Cells in Autoimmune Diseases. 2021 Innate lymphoid cells (ILC) are a heterogeneous group of immune cells characterized by lymphoid morphology and cytokine profile similar to T cells but which do not express clonally distributed diverse antigen receptors. These particular cells express transcription factors and cytokines reflecting their similarities to T helper (Th)1, Th2, and Th17 cells and are therefore referred to as ILC1, ILC2, and ILC3. Other members of the ILC subsets include lymphoid tissue inducer (LTi) and regulatory ILC (ILCreg). Natural killer (NK) cells share a common progenitor with ILC and also exhibit a lymphoid phenotype without antigen specificity. ILC are found in low numbers in peripheral blood but are much more abundant at barrier sites such as the skin, liver, airways, lymph nodes, and the gastrointestinal tract. They play an important role in innate immunity due to their capacity to respond rapidly to pathogens through the production of cytokines. Recent evidence has shown that ILC also play a key role in autoimmunity, as alterations in their number or function have been identified in systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Here, we review recent advances in the understanding of the role of ILC in the pathogenesis of autoimmune diseases, with particular emphasis on their role as a potential diagnostic biomarker and as therapeutic targets.
35200132 How do central sensitisation features affect symptoms among patients with rheumatoid arthr 2022 Feb 1 OBJECTIVES: Central sensitivity syndrome (CSS) comprises various symptoms caused by central sensitisation (CS). Using the central sensitisation inventory (CSI), a screening questionnaire developed for detecting CSS, this syndrome was recently identified in patients with long-standing rheumatoid arthritis (RA). However, the descriptors of CS-related pain and the effects of CSS on symptoms in patients with rheumatoid arthritis (RA) remain unknown. We examined the characteristics of pain and influence of CSS on patient and evaluator global assessment among multiple clinical variables. METHODS: We used the central sensitisation inventory (CSI) and short-form McGill pain questionnaire to evaluate CSS and characteristics of pain in 240 outpatients with RA. Disease activity, fibromyalgia, neuropathic pain, anxiety, depression, pain catastrophising, and health-related quality of life were evaluated. We used multivariate analysis to analyse the characteristics of CS-related pain according to CSI and the effect of CSS on patient global assessment (PGA), evaluator global assessment (EGA), and PGA minus EGA among relevant clinical variables. RESULTS: In patients with RA, the main descriptors of pain according to severity of CSI scores were "sharp" and "stabbing", whereas those of pain according to disease activity were "tender" and "throbbing". CSS was associated with EGA (p=0.000, β=- 0.199) and PGA minus EGA (p=0.021, β=0.147), but not with PGA. CONCLUSIONS: In patients with RA, descriptors for CS-related pain differ from those for disease activity-related pain. CSS may have an important impact on EGA and PGA minus EGA. Additionally, CSI may be helpful in identifying why there is discordance between PGA and EGA.
35450030 Lack of Association of rs12702634 in RPA3-UMAD1 With Interstitial Lung Diseases in Japanes 2022 BACKGROUND: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1. We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association. METHODS: Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease. RESULTS: No association was detected for rs12702634 with ILD in RA (P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association (P = .0996, OR 1.52, 95% CI 0.92-2.49). CONCLUSIONS: The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.
35395934 How much preoperative flexion contracture is a predictor for residual flexion contracture 2022 Apr 8 BACKGROUND: Although total knee arthroplasty (TKA) in hemophilic arthropathy (HA) or rheumatoid arthritis (RA) can improve functional ability, the postoperative range of motion (ROM) and prosthesis durability are reduced compared with those in osteoarthritic patients. AIM: We aimed to compare (1) the pre- and postoperative flexion contracture after TKA in HA and RA, (2) the threshold of preoperative flexion contracture as a predictor of residual contracture > 15° after TKA, and (3) the survival rate. METHODS: Data from a consecutive cohort comprising 48 TKAs in HA and 92 TKAs in RA were retrospectively reviewed. The degree of flexion contracture was analyzed. Through receiver operating characteristics analysis, we aimed to determine the cutoff value of preoperative flexion contracture that increases the risk of residual contracture > 15° after TKA and compare the cutoff value in HA and RA. The survival rate was evaluated based on life table analysis and the Kaplan-Meier method. RESULTS: The degree of preoperative flexion contracture was not significantly different. The degree of postoperative residual flexion contracture was 5.6° in the HA group and 1.4° in the RA group, respectively (p < 0.001). The cutoff value of preoperative flexion contracture for residual contracture of > 15° at last-follow up was 25.0° in the HA group and 32.5° in the RA group. The 5- and 12-year survival rates were 96% and 87% in the HA and 99% and 95% in the RA group, respectively (n.s.). CONCLUSIONS: The postoperative residual flexion contracture was greater and the cutoff value of preoperative flexion contracture for residual contracture was smaller in the HA group than the RA group. Appropriate intra- and postoperative care to avoid postoperative residual contracture is required in HA patients. LEVEL OF EVIDENCE: III.
35273709 Changes in peripheral blood T lymphocyte subsets predict disease progression in patients w 2022 OBJECTIVE: To explore the correlation between abnormal changes in peripheral blood T lymphocyte subsets and disease progression in patients with active rheumatoid arthritis (RA). METHODS: This is a retrospective study, in which 53 patients with active RA were selected as the study subjects and 50 healthy people were selected as the control group. Lymphocyte subsets were determined in both arms. According to whether CD4/CD8 ratio increased, RA patients were subdivided into an elevated CD4/CD8 group and a non-elevated CD4/CD8 group, and compared to the control group. The risk factors affecting the disease progression of patients with active RA were analyzed. RESULTS: CD4(+) T lymphocyte subsets in patients with increased CD4/CD8 were significantly higher than those in healthy controls. In addition, the elevated CD4/CD8 group showed significantly CD8(+) T lymphocyte subsets than the non-elevated CD4/CD8 group and the control group (P<0.05). The CD4(+) T lymphocyte subsets in the elevated CD4/CD8 group were not significantly higher than those in the non-elevated CD4/CD8 group (P>0.05). The CD3(+) T lymphocyte subsets as well as CD19(+) B and NK lymphocyte subsets showed no significant difference among the three arms (P>0.05). In addition, CD4, CD8 and CD4/CD8 were identified to be the risk factors affecting disease progression in patients with active RA. CONCLUSIONS: When an autoimmune disorder occurs in patients with active RA, CD8(+) T lymphocyte subsets are significantly suppressed, while CD4(+) T lymphocyte subsets show different manifestations, with some patients presenting no obvious increase. In addition, CD4, CD8 and CD4/CD8 can help to indicate the risk of disease progression in patients with active RA.
35141748 The Implication of Long Non-Coding RNA Expression Profile in Rheumatoid Arthritis: Correla 2022 Feb 10 OBJECTIVE: This study aimed to investigate the linkage of long non-coding RNA (lncRNA) expression profile with etanercept response in rheumatoid arthritis (RA) patients. METHODS: PBMC samples were collected from 80 RA patients prior to etanercept treatment. Samples from 8 responders and 8 non-responders at week 24 (W24) were proposed to RNA-sequencing, then 10 candidate lncRNAs were sorted and their PBMC expressions were validated by RT-qPCR in 80 RA patients. Subsequently, clinical response by lncRNA (CRLnc) prediction model was established. RESULTS: RNA-sequencing identified 254 up-regulated and 265 down-regulated lncRNAs in W24 responders compared with non-responders, which were enriched in immune or joint related pathways such as B cell receptor signaling, osteoclast differentiation and T cell receptor signaling pathways, etc. By RT-qPCR validation: 2 lncRNAs were correlated with W4 response, 3 lncRNAs were correlated with W12 response, 7 lncRNAs were correlated with W24 response. Subsequently, to construct and validate CRLnc prediction model, 80 RA patients were randomly divided into test set (n=40) and validation set (n=40). In the test set, lncRNA RP3-466P17.2 (OR=9.743, P=0.028), RP11-20D14.6 (OR=10.935, P=0.007), RP11-844P9.2 (OR=0.075, P=0.022) and TAS2R64P (OR=0.044, P=0.016) independently related to W24 etanercept response; then CRLnc prediction model integrating these 4 lncRNAs presented a good value in predicting W24 etanercept response (AUC: 0.956, 95%CI: 0.896-1.000). However, in the validation set, the CRLnc prediction model only exhibited a certain value in predicting W24 etanercept response (AUC: 0.753, 95%CI: 0.536-0.969). CONCLUSIONS: CRLnc prediction model is potentially a useful tool to instruct etanercept treatment in RA patients.
35640116 Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: r 2022 May 28 OBJECTIVE: To examine whether a weight loss intervention program improves rheumatoid arthritis (RA) disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients. METHODS: We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with DAS28 ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention(N = 20) or control group(N = 20). Diet intervention consisted of a hypocaloric diet of 1,000-1,500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and PDUS34. Clinical disease activity, imaging, biomarkers, adipokines, and patient reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05. RESULTS: The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (p< 0.001). RAPID3 improved, serum leptin decreased, and serum adiponectin increased significantly within the diet group and between the groups (all p< 0.03). DAS28 decreased, 5.2→4.2 within the diet group (p< 0.001)(-0.51 ([95%CI; -1.01, 0.00], p= 0.056, between groups). HAQ-DI improved significantly within the diet group (p< 0.04)(p= 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS34 -2.0 [95%CI; -7.00, 3.1], p= 0.46 between groups). CONCLUSION: Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin, and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307.
34878629 Differential Changes in ACPA Fine Specificity and Gene Expression in a Randomized Trial of 2022 Apr INTRODUCTION: The biologics abatacept and adalimumab have different mechanisms of action (MoAs). We analyzed data from patients with rheumatoid arthritis treated in AMPLE (NCT00929864) to explore the pharmacodynamic effects of abatacept or adalimumab on anti-citrullinated protein antibodies (ACPAs) and gene expression. METHODS: AMPLE was a phase IIIb, 2-year, randomized, head-to-head trial of abatacept versus adalimumab. Post hoc analyses of baseline anti-cyclic citrullinated peptide-2 (anti-CCP2, an ACPA surrogate) positive (+) status and ACPA fine-specificity profiles over time, as well as transcriptional profiling (peripheral whole blood), were performed. RESULTS: Of 646 patients treated (abatacept, n = 318; adalimumab, n = 328), ACPA and gene expression data were available from 508 and 566 patients, respectively. In anti-CCP2+ patients (n = 388), baseline fine specificities for most ACPAs were highly correlated; over 2 years, levels decreased with abatacept but not adalimumab. By year 2, expression of genes associated with T cell co-stimulation and antibody production was lower for abatacept versus adalimumab; expression of genes associated with proinflammatory signaling was lower for adalimumab versus abatacept. Treatment modulated the expression of T- and B-cell gene signatures, with differences in CD8+ T cells, activated T cells, plasma cells, B cells, natural killer cells (all lower with abatacept versus adalimumab), and polymorphonuclear leukocytes (higher with abatacept versus adalimumab). CONCLUSIONS: In AMPLE, despite similar clinical outcomes, data showed that pharmacodynamic/genetic changes after 2 years of abatacept or adalimumab were consistent with drug MoAs. Further assessment of the relationship between such changes and clinical outcomes, including prediction of response, is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00929864.
35232494 Public perceptions of predictive testing for rheumatoid arthritis compared to breast cance 2022 Mar 2 BACKGROUND: There is increasing research focus on prediction and prevention of rheumatoid arthritis (RA). Information about risk of RA is increasingly available via direct-to-consumer testing. However, there is limited understanding of public perceptions around predictive testing for RA. This study explores public perceptions of predictive testing for RA in comparison to breast cancer (BC) and early-onset Alzheimer's disease (AD). METHODS: Four focus groups with 21 members of the public were conducted using hypothetical vignettes about predictive testing for each disease. Transcripts of focus group proceedings were analysed inductively using thematic analysis. RESULTS: Thematic analysis of the data produced three key themes: decision-making factors, consequences, and consumer needs. Factors suggested that might influence decision-making about predictive testing included family history, fear, and perceived severity and treatability of the illness. RA was perceived to be less severe and more treatable than BC/AD. Potential consequences of predictive testing across all diseases included lifestyle modification, planning for the future and discrimination by employers or insurers. Predictive testing for RA was perceived to have less potential for negative psychological consequences than other diseases. Participants highlighted that individuals undertaking predictive testing should be signposted to appropriate support services and receive information on the accuracy of predictive testing. It was suggested that strategies to mitigate concerns regarding communication and confidentiality of risk results are required. CONCLUSIONS: The findings of this study reflect public misunderstandings regarding RA that may impact the uptake of and responses to predictive testing, and key informational needs of individuals considering a predictive test. Predictive strategies should be accompanied by awareness-raising initiatives and informational resources.
35500218 Association of serum hepatoma-derived growth factor levels with disease activity in rheuma 2022 May 2 BACKGROUND: Hepatoma-derived growth factor (HDGF) is reported to play an important role in tumorigenesis and cancer progression. However, growing evidence indicates its participation in immune system activation. This study analyzed the relationship among serum HDGF levels, disease activity, and laboratory markers in patients with rheumatoid arthritis (RA). METHODS: Blood samples from 165 patients with RA, 42 with osteoarthritis (OA), and 28 healthy controls, were used to evaluate the serum HDGF levels. Correlations of serum HDGF levels with age, 28-joint count disease activity score (DAS28), and laboratory findings were assessed by Pearson correlation and receiver operator characteristic (ROC) curve analyses to obtain HDGF optimal cutoffs according to the disease status. Immunohistochemical staining was performed on the knee synovial tissue samples from patients with RA and OA (n = 10 each) to investigate HDGF joint expression. RESULTS: Serum HDGF levels were significantly correlated with DAS28 erythrocyte sedimentation rate (r = 0.412, p < 0.001) and C-reactive protein values (r = 0.376, p < 0.001). The optimal cutoffs of serum HDGF levels from the ROC analysis were 5.79 and 5.14 for the differentiation of active/inactive disease and remission/non-remission, respectively. The ideal cutoff of serum HDGF levels to differentiate RA and OA was determined as 5.47. Serial serum HDGF level analyses in 21 patients with RA revealed that serum HDGF levels significantly decreased after improvement in disease activity (p = 0.046). HDGF expression was not observed in the synovial tissues of the patients with RA and OA. CONCLUSION: Serum HDGF level could be a potential laboratory biomarker for the severity of RA.
35220965 Incidence and predictors of fragility fracture in postmenopausal rheumatoid arthritis pati 2022 Feb 28 BACKGROUND: Although many studies have reported the predictors of fractures in patients with rheumatoid arthritis (RA) who are not receiving anti-osteoporotic treatments or who are receiving unspecified treatments, studies focusing on the predictors of fracture in patients with RA who are currently being treated with oral bisphosphonates (BP) are quite scarce. This study aims to investigate the incidence and predictors of fragility fracture in postmenopausal patients with RA receiving oral BP. METHODS: This retrospective longitudinal observational study comprised 98 postmenopausal RA patients receiving oral BP for a minimum of 6 months between April 2015 and December 2020. The cumulative incidence of fragility fractures including vertebral and nonvertebral fractures was investigated using the Kaplan-Meier method. Cox proportional hazards analysis was used to analyze baseline predictors of future fragility fractures. To determine a cutoff value of continuous predictors, the receiver-operating characteristic curve was applied. RESULTS: Twenty patients developed fractures during the study period, with a cumulative incidence of 6.1% at 12 months, 10.5% at a median follow-up of 28 months, and 14.4% at 36 months. Multivariable Cox hazards analysis showed a history of prior vertebral fracture (hazard ratio [HR] 6.26, 95% confidence interval [CI] 1.99‒19.68, P = 0.001) and dose of methotrexate (HR 0.87, 95% CI 0.76‒0.99, P = 0.041) to be independent predictors. The cutoff value for methotrexate dose was 4 mg/week. CONCLUSIONS: We found a cumulative incidence of any fractures of 10.5% at 28 months in patients with RA currently being treated with oral BP. A history of prior vertebral fractures and methotrexate dose were positive and negative predictors for fractures, respectively. Practitioners should consider selecting another anti-osteoporotic drug in patients with RA who remain at risk despite receiving oral BP.
35422654 Bioinformatics Analysis Identified the Hub Genes, mRNA-miRNA-lncRNA Axis, and Signaling Pa 2022 OBJECTIVE: Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA-miRNA-lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA. METHODS: The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo). Perl was used to perform data merging, and R was used to perform batch correction. The "limma" package of R was used to screen differentially expressed genes, and the "clusterProfiler" package was used to perform enrichment analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network, Cytoscape was used for module analysis, and R was used to screen for hub genes. GraphPad Prism was used to plot the receiver operating characteristic curve of the hub genes. Gene set enrichment analysis and competitive endogenous RNA network analysis were performed on hub genes with the greatest diagnostic values. The hub gene with the greatest diagnostic value was verified using immunohistochemical staining. RESULTS: We obtained nine hub genes (ITGB2, VAMP8, HLA-A, PTAFR, SYK, FCER1G, HLA-DPB1, LCP2, and ACTR2) and four mRNA-miRNA-lncRNA axes (ITGB2-hsa-miR-486-3p-SNHG3, ITGB2-hsa-miR-338-5p-XIST, ITGB2-hsa-miR-5581-3p-XIST, and ITGB2-hsa-miR-1226-5p-XIST) related to the pathogenesis of RA. The nine hub genes were highly expressed, and ITGB2 had the highest diagnostic value for RA. We also identified signaling pathways related to the pathogenesis of RA: Fc epsilon Rl and chemokine signaling pathways. The immunohistochemical results showed that ITGB2 expression was significantly upregulated in RA. CONCLUSION: The hub genes, mRNA-miRNA-lncRNA axes, and signaling pathways related to RA pathogenesis identified in this study provide a new research direction for the mechanism, diagnosis, and treatment of RA.
35416951 New indicator for discordance between patient-reported and traditional disease activity ou 2022 Apr 13 OBJECTIVE: To unravel disease impact in early Rheumatoid Arthritis (RA) by separately quantifying patient-reported (PRF), clinical (CF) and laboratory (LF) factors. We propose a new indicator, the discordance score (DS), for early identification and prediction of patient's unmet needs and of future achievement of sustained remission (SR) and RA-related quality of life (QoL). METHODS: Factor-scores obtained by factor analysis in the CareRA trial, allowed to compute DS, reflecting the difference between PRF and the mean of CF and LF. Improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time points per factor-score were calculated and compared between patients achieving/not achieving sustained (week 16-104) remission (DAS28CRP < 2.6) with ANOVA. Logistic and linear regressions were used to predict SR based on previous factor and discordance scores, and QoL at year 1 and 2 based on DS at week 16. RESULTS: PRF, CF and LF scores improved rapidly within 8 weeks. PRF improved 57%, CF 90% and LF 27%, in those achieving SR, compared with 32% (PRF: p= 0.13), 77% (CF: p< 0.001) and 9% (LF: p= 0.36) in patients not achieving SR. Patients achieving SR had an AUC of 15.7, 3.4 and 4.8 for PRF, CF and LF, respectively, compared with 33.2, 10.1, and 7.2 in participants not achieving SR (p< 0.001 for all). Early discordance was associated with later factor scores, QoL, and self-efficacy. CONCLUSIONS: All factor scores improved rapidly, especially in patients achieving SR. Patient-reported burden improved less. Discordance scores could help predicting the need for additional non-pharmacological interventions to achieve SR and decrease disease impact.
35302602 Automated quantification system predicts survival in rheumatoid arthritis-associated inter 2022 Mar 18 OBJECTIVE: The prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is difficult to predict because of the variable clinical course. This study aimed to determine the prognostic value of an automated quantification system (AQS) in RA-ILD. METHODS: We retrospectively analysed the clinical data and high-resolution computed tomography (HRCT) images of 144 patients with RA-ILD. Quantitative lung fibrosis (QLF, sum of reticulation and traction bronchiectasis) and ILD (QILD; sum of QLF, honeycombing [QHC], and ground-glass opacity [QGG]) scores were measured using the AQS. RESULTS: The mean age was 61.2 years, 43.8% of the patients were male, and the 5-year mortality rate was 30.5% (median follow-up, 52.2 months). Non-survivors showed older age, higher erythrocyte sedimentation rate (ESR), and greater AQS scores than survivors. In multivariable Cox analysis, higher QLF, QHC, and QILD scores were independent prognostic factors along with older age and higher ESR. In receiver-operating characteristic curve analysis, the QLF score showed better performance in predicting 5-year mortality than the QHC and QGG scores but was similar to the QILD score. Patients with high QLF scores (≥12% of total lung volume) showed higher 5-year mortality (50% vs. 17.4%, P<0.001) than those with low QLF scores and similar survival outcome to patients with idiopathic pulmonary fibrosis (IPF). Combining with clinical variables (age, ESR) further improved the performance of QLF score in predicting 5-year mortality. CONCLUSION: QLF scores might be useful for predicting prognosis in patients with RA-ILD. High QLF scores differentiate a poor prognostic phenotype similar to IPF.