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ID PMID Title PublicationDate abstract
35181628 Integrative Analyses of Biomarkers and Potential Therapeutic Drugs for Rheumatoid Arthriti 2022 Jan OBJECTIVE: This study aims to explore key candidate genes and predict potential therapeutic agents for rheumatoid arthritis (RA). METHODS: Differentially expressed genes (DEGs) of synovial tissue in patients with RA compared with normal donors are identified by analyzing four expression profiles. Coexpressed DEGs are confirmed by Venn diagrams. Gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction network, gene-microRNAs (miRNAs) network, and gene-drugs network are interrogated to identify hub genes and discover possible therapeutic drugs. RESULTS: A total of 69 DEGs in RA synovium samples are identified. GO analysis reveals that DEGs are significantly enriched in lymphocyte activation, adaptive immune response, and leukocyte migration in biological process. The most enriched KEGG pathway is cytokine-cytokine receptor interaction. Gene set enrichment analysis shows that most genes are enriched and upregulated in interferon gamma response. The top 10 hub genes are CD27, CD2, CCL5, IL15, GZMA, CD8A, CXCL9, IL2RG, CXCL10, and LCK. Finally, a miRNA-mRNA network and a drug-mRNA network are constructed, and 105 miRNAs and 35 drugs are screened out. CONCLUSIONS: The identified hub genes and drugs may provide valuable novel markers and treatment options for diagnosis and therapy of RA.
35111160 Metabolic Enzyme Triosephosphate Isomerase 1 and Nicotinamide Phosphoribosyltransferase, T 2021 Metabolic intervention is a novel anti-rheumatic approach. The glycolytic regulator NAMPT has been identified as a therapeutic target of rheumatoid arthritis (RA), while other metabolic regulators coordinating NAMPT to perpetuate inflammation are yet to be investigated. We continuously monitored and validated expression changes of Nampt and inflammatory indicators in peripheral while blood cells from rats with collagen-induced arthritis (CIA). Gene transcriptional profiles of Nampt (+) and Nampt (++) samples from identical CIA rats were compared by RNA-sequencing. Observed gene expression changes were validated in another batch of CIA rats, and typical metabolic regulators with persistent changes during inflammatory courses were further investigated in human subjects. According to expression differences of identified genes, RA patients were assigned into different subsets. Clinical manifestation and cytokine profiles among them were compared afterwards. Nampt overexpression typically occurred in CIA rats during early stages, when iNos and Il-1β started to be up-regulated. Among differentially expressed genes between Nampt (+) and Nampt (++) CIA rat samples, changes of Tpi1, the only glycolytic enzyme identified were sustained in the aftermath of acute inflammation. Similar to NAMPT, TPI1 expression in RA patients was higher than general population, which was synchronized with increase in RFn as well as inflammatory monocytes-related cytokines like Eotaxin. Meanwhile, RANTES levels were relatively low when NAMPT and TPI1 were overexpressed. Reciprocal interactions between TPI1 and HIF-1α were observed. HIF-1α promoted TPI1 expression, while TPI1 co-localized with HIF-1α in nucleus of inflammatory monocytes. In short, although NAMPT and TPI1 dominate different stages of CIA, they similarly provoke monocyte-mediated inflammation.
35435192 [Validation of the Pollard' s classification criteria (2010) for rheumatoid arthritis pati 2022 Apr 18 OBJECTIVE: To evaluate the sensitivity and specificity of Pollard' s classification criteria(2010) for the diagnosis of rheumatoid arthritis (RA) patients withfibromyalgia (FM) in Chinese patients, and to assess the clinical features and psychological status of RA-FM patients in a real-world observational setting. METHODS: Two hundred and two patients with rheumatoid arthritis were enrolled from the outpatients in Rheumatology and Immunology Department in Peking University People' s Hospital. All the patients were evaluated whether incorporating fibromyalgia translation occured using the 1990 American College of Rheumatolgy (ACR)-FM classification criteria. Forty two RA patients were concomitant with FM, while the other one hundred and sixty RA patients without FM were set as the control group. RESULTS: There was no significant difference in general demography between the two groups (P>0.05). In this study, the Pollard' s classification criteria (2010) for RA-FM in Chinese patients had a high sensitivity of 95.2% and relatively low specificity of 52.6%. Compared with those patients without FM, RA patients with FM (RA-FM patients) had higher Disease Activity Scale in 28 joints (DAS-28) score (5.95 vs. 4.38, P=0.011) and much more 28-tender joint counts (TJC) (16.5 vs.4.5, P < 0.001).RA-FM patients had worse Health Assessment Questionnaire (HAQ) score (1.24 vs. 0.66, P < 0.001) and lower SF-36 (28.63 vs. 58.22, P < 0.001). Fatigue was more common in RA-FM patients (88. 1% vs. 50.6%, P < 0.001) and the degree of fatigue was significantly increased in RA-FM patients (fatigue VAS 5.55 vs. 3.55, P < 0.001). RA-FM patients also had higher anxiety (10 vs.4, P < 0.001) and depression scores (12 vs.6, P < 0.001). erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), morning stiffness time and 28-swollen joint counts (SJC) showed no difference between these two groups. CONCLUSION: The Pollard' s classification criteria (2010) for RA-FM are feasible in Chinese rheumatoid arthritis patients. The Pollard' s classification criteria is highly sensitive in clinical application, while the relativelylow specificity indicates that various factors need to be considered in combination. RA patients with FM result in higher disease activity, worse function aland psychological status. RA patients with FM also have poorer quality of life. DAS-28 scores may be overestimated in RA patients with FM. In a RA patient thatdoes not reach remission, the possibility of fibromyalgia should be con-sidered.
34251302 Local adaptation of recommendation-based materials for shared decision-making and manageme 2022 May OBJECTIVES: To describe local adaptations of materials derived from evidence-based recommendations in a training programme in rheumatoid arthritis (RA). METHODS: The eRA (evolving the management of rheumatoid arthritis) programme generated shared decision-making practises and a checklist for managing comorbidity in RA, among others, at the international level. Unmet needs in RA management were first identified and prioritised. Then educational materials were designed and developed to address these gaps. These materials were evaluated in detailed and discussed in small regional groups by practicing rheumatologists. Voting, open discussions and recommendations were extracted from the meetings. RESULTS: Thirty-five Spanish rheumatologists discussed a comorbidity checklist and a shared decision-making tool. The results of the local meetings were synthesised as (1) a judicious commitment to check agreed comorbidities, and (2) a list of barriers and facilitators for the implementation of shared decision making in the local settings. With regards to ways to implement the agreed list and periodicity, two issues stand-out: (1) patient education and (2) the need of easy access to information and the use of local organisational systems in place. With respect to shared decision-making, issues raised included messages for self-awareness, challenges, and practical facilitators. CONCLUSIONS: Discussion, adaptation, and planning are needed before implementing any evidence-based recommendation and materials if we want to achieve a successful implementation. Further studies should demonstrate whether this initiative was successful in achieving the goals of improved patient care. Our experience could be used as a guidance or example for implementation elsewhere.
35464423 Bioinformatics and System Biology Approach to Identify the Influences of COVID-19 on Rheum 2022 BACKGROUND: Severe coronavirus disease 2019 (COVID -19) has led to a rapid increase in mortality worldwide. Rheumatoid arthritis (RA) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas the molecular mechanisms underlying RA and CVOID-19 are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19 and RA using bioinformatics and a systems biology approach. METHODS: Two Differentially expressed genes (DEGs) sets extracted from GSE171110 and GSE1775544 datasets were intersected to generate common DEGs, which were used for functional enrichment, pathway analysis, and candidate drugs analysis. RESULTS: A total of 103 common DEGs were identified in the two datasets between RA and COVID-19. A protein-protein interaction (PPI) was constructed using various combinatorial statistical methods and bioinformatics tools. Subsequently, hub genes and essential modules were identified from the PPI network. In addition, we performed functional analysis and pathway analysis under ontological conditions and found that there was common association between RA and progression of COVID-19 infection. Finally, transcription factor-gene interactions, protein-drug interactions, and DEGs-miRNAs coregulatory networks with common DEGs were also identified in the datasets. CONCLUSION: We successfully identified the top 10 hub genes that could serve as novel targeted therapy for COVID-19 and screened out some potential drugs useful for COVID-19 patients with RA.
34424413 Incidence of and risk factors for spondylolisthesis, scoliosis, and vertebral fracture in 2022 Jan INTRODUCTION: Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study. MATERIALS AND METHODS: The study cohort comprised 110 patients with RA from the 'analysis of factors for RA spinal disorders (AFFORD)' study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey. RESULTS: The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio [aOR] 4.81, p = 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87, p = 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without. CONCLUSION: The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.
35107652 A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthri 2022 Jun OBJECTIVES: Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and variants of genes playing a critical role in both immune response and bone homeostasis among patients with RA. METHODS: IRAK-1 rs3027898, IRAK-2 rs3844283, IRAK-2 rs708035, IFIH1 rs1990760, CD40 rs48104850, TNFAIP3 rs2230926, and miR146-a rs2910164 were genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). RESULTS: Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. Among all the SNPs assessed, only CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR = 0.31, 95% CI = 0.16-0.59, p = 3.84 × 10(-4)). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788 ± 0.136 versus 0.826 ± 0.146 g/cm(2), p = 0.001). IRAK-1 rs3027898, IRAK-2 rs3844283, rs708035, IFIH rs1990760, TNFAIP3 rs2230926, and miR146-a rs2910164 were not found to be associated with SBL. CONCLUSION: This study for the first time ever demonstrated an association between a CD40 genetic variant and SBL among patients with RA. KEY POINTS: • CD40 rs4810485 GG genotype is associated with decreased BMD among patients with RA. • CD40 rs4810485 might serve as a genetic marker for SBL in RA. • CD40 genetic variations might be integrated in future development of more effective therapeutic interventions for prevention of SBL in RA.
34033729 Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA c 2022 Mar Difficult-to-treat rheumatoid arthritis (D2T RA) is a multifactorial condition in which disease activity of RA persists despite consecutive treatment with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). To evaluate the prevalence and predictive risk factors of D2T RA in our institution, a single-center, retrospective study was conducted. Medical records of RA patients, who visited our hospital from 2011 to 2020 and had a follow-up of more than 6 months, were retrospectively reviewed. D2T RA was defined as RA with a disease activity score of 28 - erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or higher at the last visit, despite the use of at least two b/tsDMARDs. A logistic regression model was used to identify risk factors. A total of 672 patients were enrolled. The mean age at disease onset was 52.1 years and females were dominant (76.3%). After a mean follow-up of 46.6 months, patients with D2T RA accounted for 7.9% of overall patients. Multivariate analysis identified high rheumatoid factor (RF) levels (≥156.4 IU/mL, odds ratio [OR]: 1.95), DAS28-ESR (OR: 1.24), and coexisting pulmonary disease (OR: 2.03) as predictive risk factors of D2T RA. In conclusion, high RF levels, high DAS28-ESR, and coexisting pulmonary disease at baseline can predict the development of D2T RA.
34655002 Metabolic syndrome and its effect on the outcomes of rheumatoid arthritis in a multi-ethni 2022 Mar INTRODUCTION: Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes. AIM: We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes. METHOD: Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients' demographics with MetS and MetS with RA outcomes. RESULTS: The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR 1.06 [95% CI 1.04-1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02-3.09]), or Indian ethnicity (OR 3.07 [95% CI 1.68-5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease. CONCLUSION: The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease.
35577477 Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body 2022 May OBJECTIVE: Tofacitinib is an oral Janus kinase for the treatment of rheumatoid arthritis (RA). This post hoc analysis assessed whether baseline body mass index (BMI) impacts tofacitinib efficacy in patients with RA. METHODS: Pooled data from six phase 3 studies in patients receiving tofacitinib 5 mg (N=1589) or 10 mg (N=1611) twice daily or placebo (advancing to active treatment at months 3 or 6; N=680), ±conventional synthetic disease-modifying antirheumatic drugs, were stratified by baseline BMI (<25, 25 to <30, ≥30 kg/m(2)). Endpoints (through to month 6) were assessed descriptively: American College of Rheumatology 20/50/70 response rates; changes from baseline (∆) in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), DAS28-4(C-reactive protein), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) and pain; and proportions of patients achieving DAS28-4(ESR) ≥1.2 and HAQ-DI ≥0.22 decreases from baseline, low disease activity (DAS28-4(ESR) ≤3.2 or CDAI ≤10) and radiographic non-progression (Δmodified Total Sharp Score ≤0.5; months 12 and 24). Estimates were adjusted using multivariable models for selected outcomes. Univariate/multivariable regression analyses determined predictors of month 6 outcomes. RESULTS: Of 3880 patients included, 1690 (43.6%), 1173 (30.2%) and 1017 (26.2%) had baseline BMI <25, 25 to <30 and ≥30 kg/m(2), respectively. Tofacitinib showed greater efficacy improvements versus placebo in each BMI category. Differences in efficacy outcomes (adjusted and unadjusted) were generally not clinically meaningful across BMI categories within treatment groups. In regression analyses, BMI was not consistently associated with selected outcomes. CONCLUSIONS: Baseline BMI did not consistently affect tofacitinib response suggesting that tofacitinib is an effective oral treatment option for adults with moderate to severe RA regardless of baseline BMI, including patients with BMI ≥30 kg/m(2). TRIAL REGISTRATION NUMBERS: NCT00814307, NCT01039688; NCT00960440; NCT00847613; NCT00856544; NCT00853385.
34897196 Arthroscopic Synovectomy of the Wrist in Patients With Rheumatoid Arthritis: A Systematic 2022 Mar 1 BACKGROUND: Rheumatoid arthritis (RA) of the wrist can lead to loss of wrist function and progressive joint destruction if inadequately treated. Arthroscopic synovectomy of the wrist may prove a valuable treatment for local inflammation. OBJECTIVE: The aim of this study was to perform a systematic review evaluating functional outcomes and pain following arthroscopic synovectomy of the wrist in RA patients. METHODS: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. MEDLINE, EMBASE, The Cochrane Library, Web of Science, and Google Scholar were searched for studies describing pain or functional outcomes following arthroscopic synovectomy of the wrist in RA patients (CRD42021270846). Risk of bias was assessed using the Methodological Index for Non-Randomized Studies. Data collection included patient characteristics, pain scores, wrist function questionnaires, secondary surgery, and complications. RESULTS: Six noncomparative cohort studies were included, with a total of 153 arthroscopic synovectomies. Disease duration of RA ranged from 32 to 89 months, and radiographic progression was mild to moderate. The Methodological Index for Non-Randomized Studies scores ranged from 8 to 10 out of 16. Mean follow-up ranged from 21 to 95 months. Improvements were seen in pooled mean visual analog scale pain score (from 7.7 to 2.2, p < 0.05), pooled mean Modified Mayo Wrist Score (from 43.3 to 70.4, p < 0.05), and the Disability of the Arm, Shoulder, and Hand (from 67.5 to 36.5, p < 0.05). Two complications occurred, and 5 patients required secondary surgery. CONCLUSIONS: There is limited evidence suggesting that arthroscopic synovectomy of the wrist improves wrist function and pain in patients with RA, with few complications. In centers with arthroscopic expertise, it can be considered as a treatment option.
35462572 A retrospective study of the efficacy of JAK inhibitors or abatacept on rheumatoid arthrit 2022 Jun OBJECTIVES: To examine the effectiveness of Janus-kinase inhibitors (JAKis) or abatacept (ABA) in patients with rheumatoid arthritis-interstitial lung disease (RA-ILD). METHODS: Patients with RA-ILD receiving JAKis or ABA were retrospectively evaluated at baseline and after 18 months of treatment. A computer-aided method (CaM) was used to assess the extent of high-resolution computed tomography (HRCT) fibrosis percentage. According to HRCT fibrosis changes, patients were classified as "worsened" (progression of 15% or more), "stable" (changes within 15%) or "improved" (reduction of 15% or more). Correlations between RA characteristics and JAKis or ABA responses were studied using a multivariate regression model. RESULTS: Seventy-five patients (69.3% women) were evaluated, 31 received a JAKi while 44 received ABA. In the JAKis group, five patients (16.1%) showed RA-ILD progression, 20 patients (64.5%) were considered stable, and six patients (19.4%) demonstrated RA-ILD improvement. In the ABA group, five patients (11.3%) showed RA-ILD progression, 32 patients (72.7%) were stable, and seven patients (16.0%) demonstrated RA-ILD improvement. In both groups, the percentage of current smokers was different between those classified as "worsened" and those classified as "improved/stable" (p = 0.01). In multivariate regression analysis, current smoking habit (p = 0.0051) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in ABA-treated patients, whereas in JAKis-treated patients, the only RA-ILD progression-related variable was disease duration of RA (p < 0.001). CONCLUSIONS: Treatment with JAKis or ABA was related to stability or improvement of RA-ILD in 83.9% and 88.6% of patients, respectively. RA duration is the only variable associated with worsening RA-ILD in JAKis-treated patients.
35023331 Inflammation-Triggered Supramolecular Nanoplatform for Local Dynamic Dependent Imaging-Gui 2022 Mar The aging of population has resulted in a significant increase in the prevalence of rheumatoid arthritis (RA), which is a persistent and recurrent synovial inflammation caused by abnormal immune activation. Herein, the authors designed an inflammation-triggered disassembly (ITD) nanoplatform by a supramolecular assembly method, which controls the decomposition and drug release through changes in cytokine concentrations and redox potentials during the onset of arthritis, and its dual-targeted synergistic effect on collagen-induced arthritis (CIA) rats resulted in higher cell death rate and immunosuppressive rate. Meanwhile, they propose the local dynamic dependent imaging (LDDI) technology to diagnose the disease status, which may produce corresponding changes with the fluctuation of inflammatory activity and improve the accuracy of dual-target therapy by monitoring the synovial changes through in situ photoactivation of the second near infrared light (NIR-II). Very importantly, histological analysis shows that ITD strategy relieved joint destruction and cartilage degeneration and its clinical score is similar to that of the healthy group. Their work provides an effective strategy for the early diagnosis and treatment of acute and chronic inflammation diseases, which can interfere to abnormal immune activation, rather than affecting the normal function of immune system.
34369363 Plasma micro-RNA-22 is associated with disease activity in well-established rheumatoid art 2022 May OBJECTIVES: Micro-RNAs (miRNAs) are an endogenous small, single-stranded, non-coding RNAs with a 18-25 nucleotide long and have been reported as potential extracellular biomarkers of various diseases. They mainly decrease the gene expression by inhibiting the translation or cause mRNA destabilisation. The aim of our study was to identify miRNAs whose concentration may be associated with severity of rheumatoid arthritis (RA). METHODS: A total of 74 unrelated individuals, 50 with RA and 24 in a control group were enrolled to the study. Real-time PCR was used to evaluate the plasma concentration levels of 8 miRNAs: miR-26a, miR-125b, miR-20b, miR-22, miR-221, miR-17, miR-93, miR-106b. RESULTS: The logistic regression results showed that miR-22 (p=0.0003) and miR-26a (p=0.049) may be the most important molecules distinguishing RA patients and healthy controls. Moreover, the quantity of miR-22 was different between rheumatoid factor (RF)-positive and RF-negative patients (p=0.04). CONCLUSIONS: In this study we demonstrated for the first time that plasma concentration of miR-22 may be considered as a potential molecular marker associated with disease activity.
35169224 Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis. 2022 Feb Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.
35304503 Identification of hub genes and transcription factors in patients with rheumatoid arthriti 2022 Mar 18 The aim of this study was to explore the overlapping key genes, pathway networks and transcription factors (TFs) related to the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. The gene expression profiles of RA and atherosclerosis were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between RA and atherosclerosis were identified. The biological roles of common DEGs were explored through enrichment analysis. Hub genes were identified using protein-protein interaction networks. TFs were predicted using Transcriptional Regulatory Relationships Unraveled by Sentence Based Text Mining (TRRUST) database. The hub genes and TFs were validated with other datasets. The networks between TFs and hub genes were constructed by CytoScape software. A total of 131 DEGs (all upregulated) were identified. Functional enrichment analyses indicated that DEGs were mostly enriched in leukocyte migration, neutrophil activation, and phagocytosis. CytoScape demonstrated 12 hub genes and one gene cluster module. Four of the 12 hub genes (CSF1R, CD86, PTPRC, and CD53) were validated by other datasets. TRRUST predicted two TFs, including Spi-1 proto-oncogene (SPI1) and RUNX family transcription factor 1(RUNX1). The expression of RUNX1 was validated with another dataset. Our study explored the common pathogenesis of RA and atherosclerosis. These results may guide future experimental research and clinical transformation.
35041111 Importance of baseline musculoskeletal ultrasound findings in the prognosis of rheumatoid 2022 Mar OBJECTIVES: To investigate the prognostic value of baseline musculoskeletal ultrasound (MSUS) findings for rheumatoid arthritis (RA). METHOD: We retrospectively analyzed 138 patients with RA. Patients' first MSUS record was considered as the baseline expression. The subsequent MSUS changes that showed alleviation or progression were regarded as the cutoff point. Grayscale ultrasound (GSUS) synovitis, power Doppler ultrasound (PDUS) synovitis, PDUS tenosynovitis (TS), and bone erosion were scored using a semi-quantitative scale. According to the ultrasound (US) results of the cutoff point, patients were divided into the alleviation group and the progression group. Laboratory results (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], rheumatoid factor [RF], anticyclic citrullinated peptide [anti-CCP] antibody, and anti-keratin antibody [AKA]), disease activity score in 28 joints (DAS28)-ESR, and US scores were compared between the two groups to analyze the prognostic value of US findings in RA. RESULTS: The alleviation group had higher levels of CRP, synovitis, TS, GSUS synovitis, PDUS synovitis, PDUS TS, and US total scores at baseline than the progression group (p < 0.05). The alleviation group received more aggressive treatment in their initial approach than the progression group (p < 0.05). The frequency of US examinations in the alleviation group was more than that in the progression group at follow-up (p < 0.05). Presence of baseline synovitis (OR 0.248, p = 0.006) and a higher GSUS synovitis score (OR 0.521, p = 0.006) were negatively correlated with RA progression. CONCLUSIONS: Presence of baseline synovitis and higher GSUS synovitis score do not always indicate worse prognosis of RA, which can be improved with aggressive treatment. Regular MSUS follow-up may have positive influences on prognosis. Key Points • The presence of synovitis at baseline and higher GSUS synovitis score do not necessarily imply poor prognosis of RA. • Prompt and powerful therapy and regular ultrasound follow-up can slow down the progression of RA and improve its prognosis. • Patients with slight and less arthritis at baseline might be ignored and get worse prognosis due to mild treatment strategies and irregular MSUS examination.
35273614 CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Art 2022 The overproduction of osteoclasts, leading to bone destruction in patients with rheumatoid arthritis (RA), is well established. However, little is known about the metabolic dysfunction of osteoclast precursors (OCPs) in RA. Herein, we show that increasing fatty acid oxidation (FAO) induces OCP fusion. Carnitine palmitoyltransferase IA (CPT1A), which is important for carnitine transportation and is involved in FAO in the mitochondria, is upregulated in RA patients. This metabolic change further increases the expression of clathrin heavy chain (CLTC) and clathrin light chain A (CLTA) by enhancing the binding of the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) to the promoters of CLTA and CLTC. This drives clathrin-dependent endocytosis pathway, which attenuates fusion receptors in the cellular membrane and contributes to increased podosome structure formation. This study reveals a new mechanism through which FAO metabolism participates in joint destruction in RA and provides a novel therapeutic direction for the development of drugs against bone destruction in patients with RA.
32067367 Microstructural Bone Changes Are Associated With Broad-Spectrum Autoimmunity and Predict t 2022 Mar OBJECTIVE: To assess if microstructural bone lesions in individuals at risk of developing rheumatoid arthritis (RA) are related to the spectrum of anti-modified protein antibodies (AMPAs) and affect the risk of developing RA. METHODS: Cortical microchannels as well as cortical and trabecular bone mineral density (BMD) volumes (expressed as mg hydroxyapatite/cm(3) ) were analyzed by high-resolution peripheral quantitative computed tomography of the hand joints of individuals at risk of RA. AMPA response was profiled, including reactivities against citrullinated proteins (vimentin, enolase, and fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed up for the development of RA. RESULTS: Subjects at risk of developing RA (n = 75) who had broad-spectrum AMPAs (6-8 reactivities) had significantly more severe microstructural changes, including a higher mean ± SD number of cortical microchannels per joint (95 ± 3) and lower total volumetric BMD (vBMD; 265 ± 45), trabecular vBMD (176 ± 42), and cortical vBMD (585 ± 138), than those with moderate AMPA reactivity (3-5 reactivities) (number of cortical microchannels, 79 ± 30; total vBMD, 293 ± 33; trabecular vBMD, 195 ± 32; and cortical vBMD, 627 ± 91) and those with narrow AMPA reactivity (1-2 reactivities) (number of cortical microchannels, 47 ± 20; total vBMD, 311 ± 34; trabecular vBMD, 211 ± 30; and cortical vBMD, 674 ± 56). Progressors to RA had significantly higher numbers of cortical microchannels (103 ± 30 versus 71 ± 35) and lower bone volume (258 ± 37 versus 295 ± 34) compared to nonprogressors. Furthermore, rate of progression to RA was high in subjects with broad AMPA reactivity (48%) versus those with medium AMPA reactivity (26%) or narrow AMPA reactivity (0%), as well as in those with a high number of cortical microchannels (44%) versus those with a low number of cortical microchannels (10%). CONCLUSION: Microstructural changes in individuals at risk of RA are associated with broad-spectrum autoimmunity and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.
34980225 Validation of an algorithm to identify incident interstitial lung disease in patients with 2022 Jan 3 BACKGROUND/PURPOSE: Interstitial lung disease (ILD) is an important problem for patients with rheumatoid arthritis (RA). However, current approaches to ILD case finding in real-world data have been evaluated only in limited settings and identify only prevalent ILD and not new-onset disease. Our objective was to develop, refine, and validate a claims-based algorithm to identify both prevalent and incident ILD in RA patients compared to the gold standard of medical record review. METHODS: We used administrative claims data 2006-2015 from Medicare to derive a cohort of RA patients. We then identified suspected ILD using variations of ILD algorithms to classify both prevalent and incident ILD based on features of the data that included hospitalization vs. outpatient setting, physician specialty, pulmonary-related diagnosis codes, and exclusions for potentially mimicking pulmonary conditions. Positive predictive values (PPV) of several ILD algorithm variants for both prevalent and incident ILD were evaluated. RESULTS: We identified 234 linkable RA patients with sufficient data to evaluate for ILD. Overall, 108 (46.2%) of suspected cases were confirmed as ILD. Most cases (64%) were diagnosed in the outpatient setting. The best performing algorithm for prevalent ILD had a PPV of 77% (95% CI 67-84%) and for incident ILD was 96% (95% CI 85-100%). CONCLUSION: Case finding in administrative data for both prevalent and incident interstitial lung disease in RA patients is feasible and has reasonable accuracy to support population-based research and real-world evidence generation.