A bibliometric analysis of miRNAs in rheumatoid arthritis from 2001 to 2022: Research hotspots and trends.

BACKGROUND: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. METHODS: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H-index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. RESULTS: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H-index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih-hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high-frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR-146a and miR-155. CONCLUSIONS: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR-146a and miR-155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration.

High prevalence of radiographic erosions in early, untreated PsA: results from the SpARRO cohort.

AIMS: To investigate the prevalence and distribution of bone erosions in an early psoriatic arthritis (PsA) population using conventional radiography (CR) and to explore the agreement between CR and ultrasound (US) detected bone erosions. METHODS: Newly diagnosed, treatment naïve PsA patients fulfilling the ClASsification for Psoriatic Arthritis (CASPAR) classification criteria of ≤5 years symptom duration were recruited as part of the Leeds Spondyloarthropathy Register for Research and Observation and underwent CR and US examination of hands and feet. RESULTS: Overall, 4655 hand and feet joints were assessed in 122 patients. CR erosions were detected in 24.6% (n=30) with lowest prevalence seen below 8 months of symptoms (17.5% vs 24.3%>24 months). The number of erosions was higher on CR (1.55% (63/4,655); US 1.04% (34/3,270)), with 5th metatarsophalangeal (MTP) joint being the most affected site in both CR (5.21% (11/211)) and US (7.14% (15/210)). Erosions in CR were more evenly distributed compared with US where three-quarters of the total number of bone erosions were detected in wrists, second metacarpophalangeal (MCP) and fifth MTP joints. Most joints had almost perfect prevalence-adjusted bias-adjusted kappa values ranging from 0.91 to 1. CONCLUSIONS: Erosions were seen in a quarter of patients with newly diagnosed, untreated PsA with a declining trend around the 8-month symptom duration cut-off. High levels of agreement between CR and US were seen with CR detecting more erosions. A focused US assessment of the wrist, second MCP and fifth MTP joints may be useful to detect bone erosions in early PsA.

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test.

OBJECTIVES: To investigate the role of third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in predicting progression to inflammatory arthritis (IA) in individuals with new musculoskeletal (MSK) symptoms and a negative second-generation anti-CCP antibody test (anti-CCP2-). METHODS: 469 anti-CCP2- individuals underwent baseline anti-CCP3 testing (QUANTA Lite CCP3; Inova Diagnostics) and received a post enrolment 12-month questionnaire. A rheumatologist confirmed or excluded diagnosis of IA. Univariable/multivariable analyses were performed to assess the value of anti-CCP3 in predicting IA development in these anti-CCP2- individuals. RESULTS: Only 16/469 (3.4%) anti-CCP2- individuals had a positive anti-CCP3 test. Of these 16 individuals, 4 developed IA. In addition, 61/469 (13.0%) anti-CCP2- individuals self-reported, to have developed, IA. Progression was confirmed in 43/61 of them (70.5%); of whom 30/43 (69.8%) and 13/43 (30.2%) were given a diagnosis of IA and rheumatoid arthritis (RA), respectively. In qualitative univariable analysis, anti-CCP3 positivity was associated with self-reported progression (p<0.01) and IA (p=0.03), but not with RA. Anti-CCP3 levels differed significantly between progressors and non-progressors (p<0.01) for all three categories. At the manufacturer's cut-off, OR for progression ranged from 2.4 (95% CI 0.5 to 18.6; RA) to 7.5 (95% CI 2.3 to 24.0; self-reported progression). Interestingly, when cut-offs for anti-CCP3 were optimised, lower values (≥5 units) significantly increased the OR for progression in all three categories. In multivariable analysis, anti-CCP3 positivity at the manufacturer's cut-off did not remain associated with IA progression, while this lower cut-off value (≥5 units) was associated with diagnosis of RA (p=0.02). CONCLUSIONS: Anti-CCP3 testing could improve the prediction of IA development in anti-CCP2- individuals with new MSK symptoms.

Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients.

BACKGROUND: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). METHODS: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. RESULTS: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators. CONCLUSION: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.

Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these "at-risk" stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA. METHODS: Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables. RESULTS: Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, "mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations." In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs. CONCLUSIONS: Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.

ASSOCIATION OF MPV AND RDW WITH DISEASE ACTIVITY IN PATIENT WITH RHEUMATOID ARTHRITIS.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation of the synovial joints. Disease activity assessment plays a crucial role in guiding treatment decisions and monitoring disease progression in RA patients. Thus, the current study examines the association between Mean Platelet Volume (MPV), Red Cell Distribution Width (RDW), and disease activity in RA patients. A total of 100 patients were included following the inclusion and exclusion criteria. All participants underwent physical examination and laboratory tests. Disease activity was assessed using the Disease Activity Score 28 (DAS28). The cut-off levels for RDW and MPV were 14.8 and 11.25, respectively. However, a significant association was observed between RDW levels and DAS28, indicating that the group with RDW ≤14.8% displayed higher DAS compared to the RDW >14.8% group. Also, MPV levels did not exhibited statistically significant variations. RDW levels did not show significant disparities among patients with different comorbidities. There is a significant correlation exists between RDW and disease activity in RA exists. Moreover, RDW can be utilized in clinical settings to monitor disease activity effectively. Since RDW is routinely included in standard blood tests, it is cost-effective and more convenient for treating RA cases.

Classification of rheumatoid arthritis: is it time to revise the criteria?

Classification criteria have been developed for rheumatoid arthritis (RA) and other rheumatic diseases in order to gather a homogeneous patient population for clinical studies and facilitate the timely implementation of therapeutic measures. Although classification criteria are not intended to be used for diagnosis, they are frequently used to support the diagnostic process in clinical practice, including clinical decision-making. The 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for RA are capable of identifying the majority of symptomatic patients with RA already in the earliest stages of the disease who are not yet showing radiographic changes. These patients will also profit from the early implementation of therapy with disease-modifying antirheumatic drugs (DMARDs). However, the risk of misclassification is higher as compared with the former 1987 ACR criteria, which were considerably less sensitive to the recognition of patients with early RA. Of note, the presence of rheumatoid factors (RFs) and anticitrullinated protein antibodies (ACPAs) has been attributed equal weight in the 2010 ACR/EULAR criteria and may contribute up to 50% of the score needed for being classified as RA. However, while ACPAs have been proven to be the most specific serological markers of RA, the specificity of RF is moderate, especially at lower titres. This may lead to the misclassification of RF-positive patients and, consequently, the unjustified implementation of DMARD therapy. Therefore, issues arise on how comprehensive the criteria should be and whether they should be updated and adapted to findings from the past two decades that might increase both their specificity and sensitivity.

A novel diagnostic model based on lncRNA PTPRE expression, neutrophil count and red blood cell distribution width for diagnosis of seronegative rheumatoid arthritis.

Diagnosis of seronegative rheumatoid arthritis (SNRA) is difficult due to the lack of diagnostic markers. The study aims to construct a novel diagnostic model based on long noncoding RNAs (lncRNAs) expression and laboratory indicators to provide a new idea for diagnostic methods of SNRA. Differentially expressed lncRNAs in peripheral blood cells of RA patients were screened through eukaryotic long noncoding RNA sequencing and validated by quantitative real-time PCR. Meanwhile, the correlation between lncRNAs expression and laboratory indicators was analyzed. The diagnostic value was evaluated by receiver operating characteristic curve analysis. Finally, combined with laboratory indicators, a diagnostic model for SNRA was constructed based on logistic regression and visualized by nomogram. Expression of ADGRE5, FAM157A, PTPN6 and PTPRE in peripheral blood was significantly increased in RA than healthy donors. Meanwhile, we analyzed the relationship between lncRNAs and erythrocyte sedimentation rate, C-reactive protein and CD4 + T cell-related cytokines and transcription factors. Results showed that FAM157A and PTPN6 were positively related to RORγt, and negatively related to GATA3. Moreover, PTPRE has potential discrimination ability between SNRA and healthy donor (AUC = 0.6709). Finally, we constructed a diagnostic model based on PTPRE, neutrophil count and red blood cell distribution width (RDW). The AUC of the model was 0.939 and well-fitted calibration curves. Decision curve analysis indicated the model had better predict performance in SNRA diagnosis. Our study constructed a novel diagnostic model based on PTPRE, neutrophil count and RDW which may serve as a potential tool for the diagnosis of SNRA.

Development and validation of the rheumatoid arthritis scale among the system of quality of life instruments for chronic diseases QLICD-RA (V2.0).

Rheumatoid Arthritis is a more serious threatening to people and suitable for QOL measurement. A few specific QOL instruments are available without considering Chinese culture. The present study was aimed to develop and validate the Rheumatoid Arthritis Scale among the System of Quality of Life Instruments for Chronic Diseases (QLICD-RA V2.0). The data collected from 379 patients with RA was used to evaluate the psychometric properties of the scale. The reliability was evaluated by the internal consistency Cronbach's α, test-retest reliability Pearson correlation r and intra-class correlation (ICC). We evaluated the construct validity and criteria-related validity by correlation analysis and structural equation modeling. We compared the differences in scores of QLICD-RA before and after treatment and used the Standard Response Mean (SRM) to assess the responsiveness. The results showed that the internal consistency coefficient Cronbach's α values were greater than 0.70. The correlations r and ICCs were greater than 0.80. The correlation analysis and structural equation modeling confirmed good construct validity and criterion-related validity. The SRM ranges from 0.07 to 0.27 for significant domains/facets. It concluded that QLICD-RA (2.0) is a reliable and valid instrument to measure QOL among patients with RA.

Cognitive dysfunction, depression and serum level of brain-derived neurotrophic factor (BDNF) in Egyptian patients with rheumatoid arthritis / Disfunción cognitiva, depresión y nivel sérico del factor neurotrófico derivado del cerebro (BDNF) en pacientes egipcios con artritis reumatoide

Aim of the work: To evaluate serum brain-derived neurotrophic factor (BDNF) in Egyptian patients with rheumatoid arthritis (RA) and its relation with cognitive dysfunction. Patients and methods: The study was carried out on 60 RA patients; 30 were active (group A) and 30 were non active (group B); and 30 controls (group C). RA disease activity was assessed via DAS28 tool, cognitive function via The Montreal Cognitive Assessment and depression via the PHQ depression scale. Serum BDNF levels were measured. Results: The mean age in group A was 37.8 (±9.37) years with 83.3% females, in group B was 39.97 (±8.04) years with 86.7% females and in group C was 33.17 (±3.6) years with 93.3% females. Abnormal cognitive functions test was detected in 66.7% of group A, 66.7% of group B, and in 23.3% of group C. There was a statistically significant difference in BDNF serum level between both groups of patients (1.58±0.9ng/ml for group A, 1.81±1.17ng/ml for group B) compared with the control group (3.01±1.25ng/ml, p<0.001). There was no statistically significant difference between BDNF and both disease duration and cognitive function, also no statistically significant difference regarding cognitive function, depression, and BNDF levels in patients with and without fibromyalgia. At a cut-off value of <2ng/ml, BDNF detected RA patients with cognitive dysfunction with a sensitivity of 80%, specificity of 96.67%. Conclusion: BDNF can be a potential biomarker of cognitive dysfunction in RA patients.(AU)

Objetivo: Evaluar el factor neurotrófico derivado del cerebro (BDNF) en suero en pacientes egipcios con artritis reumatoide (AR) y su relación con la disfunción cognitiva. Pacientes y métodos: El estudio se realizó en 60 pacientes con AR; 30 eran activos (grupo A) y 30 no activos (grupo B); y 30 controles (grupo C). La actividad de la enfermedad de AR se evaluó a través de la herramienta DAS28, la función cognitiva a través de la Evaluación Cognitiva de Montreal y la depresión a través de la escala de depresión PHQ. Se midieron los niveles de BDNF en suero. Resultados: La edad media en el grupo A fue de 37,8 (±9,37) años con 83,3% de mujeres, en el grupo B de 39,97 (±8,04) años con 86,7% de mujeres y en el grupo C de 33,17 (±3,6) años con 93,3% de mujeres. La prueba de funciones cognitivas anormales se detectó en 66,7% del grupo A, 66,7% del grupo B y 23,3% del grupo C. Hubo una diferencia estadísticamente significativa en el nivel sérico de BDNF entre ambos grupos de pacientes (1,58±0,9ng/mL para grupo A, 1,81±1,17ng/mL para el grupo B) en comparación con el grupo control (3,01±1,25ng/mL, p<0,001). No hubo diferencias estadísticamente significativas entre el BDNF y la duración de la enfermedad y la función cognitiva, tampoco hubo diferencias estadísticamente significativas con respecto a la función cognitiva, la depresión y los niveles de BDNF en pacientes con y sin fibromialgia. A un valor de corte de <2ng/mL, BDNF detectó pacientes con AR con disfunción cognitiva con una sensibilidad de 80% y una especificidad de 96,67%. Conclusión: BDNF puede ser un biomarcador potencial de disfunción cognitiva en pacientes con AR.(AU)

Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis.

INTRODUCTION: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined. METHODS: In a cross-sectional study of sequential RA patients with at least moderate DAS28 erythrocyte sedimentation rate disease activity, we assessed 66/68 joints for swelling and tenderness, respectively, FM American College of Rheumatology 2010 diagnostic criteria, completed PROMs for function, quality of life and mood, alongside PDUS examination of 44 joints. Statistical analysis included logistic regression modelling and regularised (lasso) logistic regression methods. RESULTS: From 158 patients, 72 (46%) patients met FM criteria, with significantly worse tender joint counts and PROMs, but no differences in PDUS compared with the non-FM group. Categorising patients by PDUS+ joint presence and/or FM criteria, we identified four distinct groups: 43 (27.2%) patients with -FM-PD, 43 (27.2%) with -FM+PD, 42 (26.6%) with +FM-PD and 30 (19%) with +FM+PD. Both FM+ groups had worse PROMs for fatigue, mood and pain, compared with the FM- groups. We were unable to develop algorithms to identify different groups. CONCLUSION: The unexpected group -FM-PD group may have peripheral nociplastic pain, not commonly recognised in rheumatology. Only 46% of patients demonstrated PDUS+ inflammation. However clinical examination and PROMs did not reliably differentiate groups, emphasising PDUS remains an important tool.

Concomitant Sjögren's disease as a biomarker for treatment effectiveness in rheumatoid arthritis - results from the Swiss clinical quality management cohort.

OBJECTIVE: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren's disease (SjD). METHODS: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders. RESULTS: We identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07-1.6]; OMA HR 1.12 [0.91-1.37]; JAKi HR 0.97 [0.62-1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46-0.84]) and JAKi (HR 0.52 [0.28-0.96]). CONCLUSION: RA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi.

Integrative analysis and validation of necroptosis-related molecular signature for evaluating diagnosis and immune features in Rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that is characterized by persistent morning stiffness, joint pain, and swelling. However, there is a lack of reliable diagnostic markers and therapeutic targets that are both effective and trustworthy. METHODS: In this study, gene expression profiles (GSE89408, GSE55235, GSE55457, and GSE77298) were obtained from the Gene Expression Omnibus database. Differentially expressed necroptosis-related genes were attained from intersection of necroptosis-related gene set, differentially expressed genes, and weighted gene co-expression network analysis. The LASSO, random forest, and SVM-RFE machine learning algorithms were utilized to further screen potential diagnostic genes for RA. Immune cell infiltration was analyzed using the CIBERSORT method. The expressions of diagnostic genes were validated through quantitative real-time PCR, western blotting, immunohistochemistry, and immunofluorescence staining in synovial tissues collected from three trauma controls and three RA patients. RESULTS: Five core necroptosis-related genes (FAS, CYBB, TNFSF10, EIF2AK2, and BIRC2) were identified as potential biomarkers for RA. Two different necroptosis patterns based on these five genes were confirmed to significantly correlated with immune cells (especially macrophages). In vitro experiments showed significantly higher mRNA and protein expression levels of CYBB and EIF2AK2 in RA patients compared to normal controls, consistent with the bioinformatics analysis results. CONCLUSION: Our study identified a novel necroptosis-related subtype and five diagnostic biomarkers of RA, revealed vital roles in the development and occurrence of RA, and offered potential targets for clinical diagnosis and immunotherapy.

Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing.

OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. RESULTS: The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94. CONCLUSIONS: This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.

Tumor Necrosis Factor Inhibitor Use Increases Birthweight in Pregnant Women With Rheumatoid Arthritis Independently of the Soluble Fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio.

BACKGROUND: To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt-1 (soluble Fms-like tyrosine kinase-1), PlGF (placental growth factor), or their impact on birthweight. METHODS AND RESULTS: sFlt-1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt-1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt-1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester-related variation in levels of sFlt-1 and PlGF, after correction for relevant confounders, the sFlt-1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt-1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54-26.29], P=0.79; sFlt-1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73-22.50], P=0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g; P=0.03), and sFlt-1 displayed a negative correlation with birthweight (r=-0.462, P<0.001) and birthweight percentile (r=-0.332, P=0.008). In TNFi users, these correlations were absent. CONCLUSIONS: TNF inhibitor use increases birthweight in pregnant women with rheumatoid arthritis independently of the sFlt-1/PlGF ratio. REGISTRATION: http://clinicaltrials.gov. Unique identifier: NCT01345071.

Evaluation of the prognostic nutritional index (PNI) as a tool for assessing disease activity in rheumatoid arthritis patients.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease of unknown exact cause, characterized by chronic inflammation. The prognostic nutritional index (PNI), reflecting albumin concentration and lymphocyte count, is a newly established inflammation-based nutritional score. This study aimed to determine the relationship between PNI and disease activity in RA patients. PATIENTS AND METHODS: This cross-sectional study included 138 RA patients who met the 2010 revised criteria of the American College of Rheumatology (ACR) for RA. PNI was calculated using the following formula: 10 × serum albumin value (g/dL) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The study population was divided into two groups: DAS28-ESR ≤ 3.2 (group 1 with remission and low disease activity) and DAS28-ESR > 3.2 (group 2 with moderate and high disease activity). RESULTS: A total of 138 patients with a mean age of 52.1 years were recruited. While the female gender was more prevalent in both groups, it was significantly higher in group 2 (p < 0.05). Group 2 exhibited a lower PNI compared to those in group 1 (42.17 ± 3.46 vs. 44.02 ± 2.92; p = 0.001). Multivariate logistic regression analyses revealed that PNI was an independent predictor of disease activity (OR, 0.850; 95% CI, 0.735-0.983; p = 0.029). ROC curve analysis determined that the optimal cutoff value of PNI for disease activity was 43.01, with a sensitivity of 69.1% and specificity of 57.7% (AUC, 0.66; 95% CI, 0.57-0.75, p = 0.001). CONCLUSION: This study demonstrates that the simple and readily available PNI could serve as an independent predictor of disease activity in rheumatoid arthritis patients. Key Points •The relationship between disease activity and the prognostic nutritional index, which is a nutritional indicator, in rheumatoid arthritis patients was investigated. •It has been shown that there is a connection between low PNI and high disease activity. •It has been shown that PNI can be used to evaluate disease severity with a simple calculation.

Promoting physical activity in rheumatoid arthritis through a physiotherapist led behaviour change-based intervention (PIPPRA): a feasibility randomised trial.

Physical activity (PA) is recommended as a key component in the management of people with rheumatoid arthritis (RA). The objective of this study was to examine the feasibility of a physiotherapist led, behaviour change (BC) theory-informed, intervention to promote PA in people with RA who have low levels of current PA. A feasibility randomised trial (ClinicalTrials.gov NCT03644160) of people with RA over 18 years recruited from outpatient rheumatology clinics and classified as insufficiently physically active using the Godin-Shephard Leisure Time Physical Activity Questionnaire. Participants were randomised to intervention group (4 BC physiotherapy sessions in 8 weeks) delivered in person/virtually or control group (PA information leaflet only). Feasibility targets (eligibility, recruitment, and refusal), protocol adherence and acceptability were measured. Health care professionals (HCPs) involved in the study and patients in the intervention and control arms were interviewed to determine acceptability. Descriptive statistics were used to analyse the data with SPSS (v27) with interviews analysed using content analysis using NVivo (v14). Three hundred and twenty participants were identified as potentially eligible, with n = 183 (57%) eligible to participate, of which n = 58 (32%) consented to participate. The recruitment rate was 6.4 per month. Due to the impact of COVID-19 on the study, recruitment took place over two separate phases in 2020 and 2021. Of the 25 participants completing the full study, 23 were female (mean age 60 years (SD 11.5)), with n = 11 allocated to intervention group and n = 14 to control. Intervention group participants completed 100% of sessions 1 & 2, 88% of session 3 and 81% of session 4. The study design and intervention were acceptable overall to participants, with enhancements suggested. The PIPPRA study to improve promote physical activity in people with RA who have low PA levels was feasible, acceptable and safe. Despite the impact of COVID-19 on the recruitment and retention of patients, the study provides preliminary evidence that this physiotherapist led BC intervention is feasible and a full definitive intervention should be undertaken. Health care professionals involved in the study delivery and the patient participants described a number of positive aspects to the study with some suggestions to enhance the design. These findings hence inform the design of a future efficacy-focused clinical trial.