Rheumatoid Arthritis Disease Research Articles

Skin tactile perception is associated with longitudinal gait performance in middle-aged and older Japanese community dwellers.

Skin tactile perception may indicate frailty in older adults. Although gait performance is crucial for diagnosing frailty, its association with skin tactile perception has not yet been explored. To examine the association between skin tactile perception and changes in step length, cadence, and gait speed in middle-aged and older adults. A longitudinal study (mean follow-up: 10.8 years) SETTING: Community-based survey PARTICIPANTS: A total of 1,403 middle-aged and older adults (aged 40-79 years, 53.6 % men) from the National Institute for Longevity Sciences-Longitudinal Study of Aging were included in this study. These participants completed the baseline survey (1997-2000) and at least two follow-up surveys (2000-2012), had no history of cerebrovascular disease, rheumatoid arthritis, or Parkinson's disease, and had complete data with no outliers in skin tactile perception measurements. Skin tactile perception was assessed using a two-point discrimination test. Step length (cm), cadence (steps/min), and gait speed (m/min) were evaluated on an 11-m walkway at a usual speed. The mean age of participants was 56.4 years. After full adjustment, mixed-effects models with splines revealed that the association between skin tactile perception and gait parameters varied with age. In adults aged 60 and above, we observed non-linear relationships between skin tactile perception and gait parameters. A consistent inflection point around 10 mm in tactile perception was identified across different age groups and gait parameters. Among community-dwelling middle-aged and older Japanese adults, skin tactile perception was associated with changes in gait parameters, particularly in those aged 60 and above. The 10-mm threshold in tactile perception may serve as a critical indicator for predicting changes in gait performance. Skin tactile perception tests may prove clinically useful for screening patients at elevated risk of impaired gait performance.

Trained immunity in chronic inflammatory diseases and cancer.

A decade after the term 'trained immunity' (TRIM) was coined to reflect the long-lasting hyper-responsiveness of innate immune cells with an epigenetically imprinted 'memory' of earlier stimuli, our understanding has broadened to include the potential implications of TRIM in health and disease. Here, after summarizing the well-documented beneficial effects of TRIM against infections, we discuss emerging evidence that TRIM is also a major underlying mechanism in chronic inflammation-related disorders such as periodontitis, rheumatoid arthritis and cardiovascular disease. Furthermore, mounting evidence indicates that the induction of TRIM by certain agonists confers protective antitumour responses. Although the mechanisms underlying TRIM require further study, the current knowledge enables the experimental development of innovative therapeutic approaches to stimulate or inhibit TRIM in a context-appropriate manner, such as the stimulation of TRIM in cancer or its inhibition in inflammatory disorders.

MAPK4 inhibits the early aberrant activation of B cells in rheumatoid arthritis by promoting the IRF4-SHIP1 signaling pathway

The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation. Using MAPK4 knockout (KO) mice, we demonstrated that MAPK4 intrinsically promotes the differentiation of marginal zone (MZ) B cells. Loss of MAPK4 in KO mice enhances proximal BCR signaling and activates the PI3K-AKT-mTOR pathway, leading to heightened B cell proliferation. Notably, B cells from MAPK4 KO mice produce significantly higher levels of IL-6, a key pro-inflammatory cytokine in RA. Furthermore, MAPK4 KO mice exhibit impaired T cell-independent humoral immune responses. Mechanistically, MAPK4 inhibits the activation of the PI3K signaling pathway in B cells by activating the IRF4-SHIP1 pathway. Treatment with the MAPK4 agonist Vacquinol-1 enhances MZ B cell differentiation in WT mice and reduces IL-6 secretion in CIA mouse models. In summary, this study reveals the diverse roles of MAPK4 in regulating of B cell functions, with potential implications for developing therapeutic strategies for RA and related autoimmune diseases.

Efficacy and safety of first-line targeted synthetic DMARDs in rheumatoid arthritis patients with chronic kidney disease.

To evaluate the efficacy and safety of first-line targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). This retrospective cohort study included 216 patients with RA prescribed their first tsDMARDs at two hospitals between 2013 and 2022. Dose reduction and contraindication guidelines for tsDMARDs according to kidney function were followed. The patients were categorised by kidney function and tsDMARD modality. The primary outcome was the 24-month drug retention rate, and the secondary outcomes were changes in the Disease Activity Score 28-C-reactive protein (DAS28-CRP) level, prednisolone dosage, and reasons for discontinuation. The 24-month drug retention rates according to the estimated glomerular filtration rate (eGFR) (≥60, 30-60, or < 30 mL/min/1.73 m2) were as follows: all tsDMARDs (46.0, 44.1, 47.1%), tofacitinib (55.9, 53.3, 66.7%), baricitinib (64.2, 42.0%), and peficitinib (36.4, 44.1, 40.0%). Even in groups with lower kidney function, the drug retention rate was maintained (adjusted hazard ratio was 1.14 (95% confidence interval, 0.81-1.62), p= 0.45). Patients had a decreased DAS28-CRP (p< 0.01) and a reduced prednisolone dosage (p< 0.01) over the six-month period following tsDMARD initiation. The incidence of herpes zoster and deep vein thrombosis (DVT) was higher in the group with an eGFR <30 mL/min/1.73 m2, but not statistically significant. tsDMARDs have demonstrated efficacy and safety in patients with RA and CKD; however, clinicians should consider the potential for herpes zoster and DVT in patients with eGFR <30 mL/min/1.73 m2.

Clinical features of inflammatory arthritis in daily practice-China's perspective.

This study aimed to analyze and compare the proportion of patients with different types of inflammatory arthritis and investigate the clinical characteristics, including symptoms and signs, medication choices, and disease activity, in the daily clinical practice of China. Patients with inflammatory arthritis were recruited from 16 Grade-A tertiary hospitals between August 2021 and April 2022. The medical profiles, encompassing sociodemographic characteristics, clinical and laboratory date, were collected. This study included 2,693 patients with arthritis, with rheumatoid arthritis (RA) accounting for the highest proportion (50.50%). Significant differences were observed in terms of age,gender, body mass index (BMI), disease duration, smoking and family history among patients with different types of inflammatory arthritis. Physical activity and cold exposure were identified as the main predisposing factors for RA, psoriatic arthritis (PsA), osteoarthritis (OA), and ankylosing spondylitis (AS), while alcohol consumption was the most common inducing factor for gout. Hypertension and hyperlipidemia were the primary concomitant diseases in RA, OA, and AS, whereas hyperuricemia and hypertension were mainly associated with gout, psoriasis and diabetes were the most common comorbidities in PsA. Peripheral joints were predominantly affected in PsA, RA, OA, and gout, while axial joints were mainly affected in AS. Methotrexate and leflunomide were the main therapeutic drugs for RA, while biologics were commonly prescribed for PsA and AS. OA and gout patients mainly utilized nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with different types of inflammatory arthritis exhibited varying predisposing factors, joint inflammation, concomitant diseases, and medication choices, highlighting the importance of individualized approaches in the clinic. Key Points • 2,693 patients classified and diagnosed with inflammatory arthritis were recruited in this study from 16 Grade-A tertiary hospitals in China between August 2021 and April 2022. • This study analyzed and compared the proportion of patients with different types of arthritis in routine clinical practice in China. • Joint inflammation, comorbidities, and medication choices were assessed among patients with the most common types of arthritis in this study. • This study also provided some epidemiologically relevant information about inflammatory arthritis patients in China.

Neutrophil extracellular traps (NETs) are increased in rheumatoid arthritis-associated interstitial lung disease

BackgroundNeutrophil extracellular trap (NET) formation has been implicated as a pathogenic mechanism in both rheumatoid arthritis (RA) and interstitial lung disease (ILD). However, the role of NETs in RA-associated ILD (RA-ILD) and the mechanisms driving NET formation remain unclear. This study aimed to assess the involvement of NETs in RA-ILD and elucidate the underlying mechanisms.MethodsSingle-cell sequencing was used to identify changes in the quantity and function of neutrophils in the lung tissue of a zymosan A (ZYM)-induced interstitial pneumonia arthritis model. Additionally, nuclear receptor 4A3 (NR4A3) interference was performed in HL-60 cells to assess its impact on NET formation and the transformation of MRC-5 cells into myofibroblasts. The clinical relevance of plasma myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (Cit-H3), and cell-free DNA was evaluated in RA-ILD patients with different imaging types via a commercial enzyme-linked immunosorbent assay (ELISA).ResultsIn the ZYM-treated SKG mouse model, which recapitulates key features of RA-ILD, an increased population of neutrophils in the lung tissue was primarily responsible for NET formation. Mechanistically, we found that interference with NR4A3 expression enhanced NET formation in HL-60 cells, which in turn promoted the differentiation of MRC-5 cells into myofibroblasts. Clinically, plasma MPO-DNA levels are elevated in patients with RA-nonspecific interstitial pneumonia (RA-NSIP), whereas Cit-H3 levels are elevated in RA-usual interstitial pneumonia (RA-UIP) patients compared with healthy subjects. ROC curve analysis further revealed that the combination of plasma MPO-DNA, rheumatoid factor (RF), and anti-citrullinated protein (anti-CCP) and the combination of Cit-H3, RF, and anti-CCP were superior diagnostic panels for NSIP and UIP in RA-ILD patients, respectively. Moreover, compared with those from healthy controls, neutrophils from patients with RA-UIP and RA-NSIP demonstrated a significantly increased ability to form NETs and induce the differentiation of MRC-5 cells into myofibroblasts. Specifically, RA-UIP patients exhibited a greater capacity for NET formation and the differentiation of MRC-5 cells into myofibroblasts than did RA-NSIP patients.ConclusionsThese findings suggest that targeting NETs may be a novel therapeutic approach for treating ILD in RA patients.

DOP013 Risk of immune mediated inflammatory diseases associated with anti-TNFs and ustekinumab in Crohn’s disease: a nationwide population-based cohort study

Abstract Background Biologics have been variously associated with an increased risk of paradoxical immune mediated inflammatory diseases (IMIDs) in patients with Crohn’s disease (CD). While this risk has been assessed in cohort studies for tumor necrosis factor inhibitors (anti-TNF), only case reports have reported the paradoxical occurrence of IMIDs in patients treated with ustekinumab. The aim of this study was to assess the risk of an incident second IMID in patients with CD treated with anti-TNF and ustekinumab. Methods We identified individuals with CD and no other IMIDs switching after a first anti-TNF to either a second anti-TNF or ustekinumab based on the French administrative healthcare databases 2008-2022. The primary outcome was the occurrence of a second IMID, including inflammatory rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and polymyalgia rheumatica), skin diseases (psoriasis, hidradenitis suppurativa, and vitiligo), neurologic diseases (multiple sclerosis, myasthenia gravis), thyroiditis, connective tissue diseases, and vasculitis. Follow-up started from treatment switch until occurrence of a second IMID, treatment withdrawal, or December 31, 2022. A lag period of 3 months was considered to minimize protopathic bias. Hazard ratios for the risk of second IMID were calculated, following 1:1 propensity score (PS) weighting, in order to control for confounders including demographics, previous and baseline IBD disease activity, co-treatment exposure, and comorbidities. Results Among 13,994 CD patients included, 10,712 (76.5%) and 3,282 (23.5%) patients were exposed to a second anti-TNF and ustekinumab, respectively. The overall proportion of women was 59.6%. Mean age at cohort entry was 38.0 (SD, 13.8) and 41.6 years (SD, 14.8) in the anti-TNF and ustekinumab groups, respectively. The median follow-up was 5.7 years (IQR, 3.3-9.1). Overall, 578 incident second IMID occurred (incidence rates: 23.2 per 1000 PY, person-years), mainly consisting in psoriasis (350, 60.6%) and ankylosing spondylitis (117, 20.2%). The cumulative incidence of second IMID after 10 years of follow-up was 9.85% (confidence interval 95% [8.84-10.85]). All covariates included in the PS model were balanced with an absolute standardized difference lower than 0.1. The risk of second IMID was lower in patients exposed to ustekinumab compared to those exposed to a second anti-TNF (HR=0.63 CI 95%[0.48-0.81], p-value&amp;lt;0.001). Conclusion Based on a population-based and propensity score weighted cohort of 13,994 CD patients, exposure to ustekinumab was associated with a lower risk of second IMID compared to anti-TNF.

Cardiovascular Risk Factor and Atherosclerosis in Rheumatoid Arthritis (RA).

To highlight advancements in managing traditional and rheumatoid arthritis (RA) specific risk factors and the impact of RA treatments on cardiovascular outcomes. Advancements in rheumatoid arthritis management have paralleled declining trends in cardiovascular disease risks. Biomarkers like CRP, Lipoprotein(a), Apolipoprotein B 100, and imaging tools such as coronary artery calcium scoring enhance cardiovascular risk stratification, particularly in intermediate-risk RA patients. While effective RA treatments, have demonstrated substantial cardiovascular benefits, subclass differences were noted in high-risk patients. Increased risk of cardiovascular disease is driven by chronic inflammation, altered lipid metabolism, and traditional risk factors. Effective RA treatment significantly lowers cardiovascular events. Standard treatment of hypertension, diabetes and hypercholesterolemia are effective and lowers RA disease activity and inflammatory markers. While RA is considered a risk enhancing state in calculating CV risk scores, currently there exists no RA disease -specific blood pressure, blood sugar or lipid targets.

Physician Views and Attitudes Regarding Tobacco-Cessation Strategies for Patients with Rheumatoid Arthritis.

In this study, we explored physicians' level of experience with patients with rheumatoid arthritis (RA) who used tobacco; their views on the effects of tobacco use on the efficacy of RA treatments; and their experiences and attitudes with respect to tobacco cessation programs. We conducted qualitative, semi-structured interviews of 20 physicians (10 primary-care physicians [PCPs] and 10 rheumatologists). The physicians had been in clinical practice for a mean of 9.9 years. Research themes included 1) risk perception of smoking, 2) cessation aids used, 3) preferences to deliver cessation programs, and 4) barriers and facilitators for tobacco cessation. For the first theme, many PCPs did not perceive smoking as influencing RA disease activity. For the second theme, most physicians supported the use of nicotine-replacement therapy and agreed that cessation-drug therapy (e.g., varenicline, bupropion) worked better than nicotine-replacement therapy or other cessation strategies, especially in patients with failed cessation attempts. For the third theme, some physicians recommended that patients join the Quitline cessation program and enroll in peer-support communities; others found educational programs informing patients about benefits of quitting and tailored with messages according to patients' specific clinical characteristics to be useful. For the fourth theme, PCPs and rheumatologists reported similar barriers to offering smoking cessation programs (e.g., lack of time, training in tobacco cessation, and financial motivation). Physicians agreed with the need for tailored, multifaceted interventions to support tobacco cessation in patients with RA. However, many perceived major barriers to helping their patients quit, some of which could be overcome by training.

Remote-Customized Telecontrol for Patients with Rheumatoid Arthritis: The iARPlus (Innovative Approach in Rheumatology) Initiative.

Objective. Telecontrol approaches for rheumatoid arthritis (RA) management aim to enhance patient outcomes. This pilot study assessed whether the Rheumatoid Arthritis Impact of Disease (RAID) approach could be used during teleconsultations to monitor RA disease activity through a web-based platform called iARPlus (Innovative Approach in Rheumatology). Methods. Forty RA patients participated in two in-person visits (baseline and 12 months) and seven teleconsultations over 12 months, collected via the iARPlus portal and accessible through an internet browser. Disease activity, at baseline and follow-up, was measured using the Clinical Disease Activity Index (CDAI) and self-reported RAID scores throughout the study. The RAID approach, developed by the European Alliance of Associations for Rheumatology (EULAR), combines key patient-reported outcomes (PROs). Results. Nineteen patients (mean age: 49.3 years) were treated with Janus kinase inhibitors (JAKis), and 21 patients (mean age: 48.1 years) received adalimumab. All patients had active disease (mean CDAI 27.9 ± 4.8). Strong correlations were found between CDAI and RAID scores at baseline (ρ = 0.809, p < 0.0001) and at follow-up (ρ = 0.789, p < 0.0001). JAKi-treated patients showed greater reductions in RAID scores, pain relief, and higher rates of disease remission compared to adalimumab-treated patients. Conclusions. RAID scores were effective in teleconsultations for assessing RA disease activity. JAKi treatment resulted in better pain control and disease activity improvement compared to adalimumab. Further studies are needed to confirm the clinical and economic benefits of telecontrol for RA management.

Biodegradable and Stimuli-Responsive Nanomaterials for Targeted Drug Delivery in Autoimmune Diseases.

Autoimmune diseases present complex therapeutic challenges due to their chronic nature, systemic impact, and requirement for precise immunomodulation to avoid adverse side effects. Recent advancements in biodegradable and stimuli-responsive nanomaterials have opened new avenues for targeted drug delivery systems capable of addressing these challenges. This review provides a comprehensive analysis of state-of-the-art biodegradable nanocarriers such as polymeric nanoparticles, liposomes, and hydrogels engineered for targeted delivery in autoimmune therapies. These nanomaterials are designed to degrade safely in the body while releasing therapeutic agents in response to specific stimuli, including pH, temperature, redox conditions, and enzymatic activity. By achieving localized and controlled release of anti-inflammatory and immunosuppressive agents, these systems minimize systemic toxicity and enhance therapeutic efficacy. We discuss the underlying mechanisms of stimuli-responsive nanomaterials, recent applications in treating diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease, and the design considerations essential for clinical translation. Additionally, we address current challenges, including biocompatibility, scalability, and regulatory hurdles, as well as future directions for integrating advanced nanotechnology with personalized medicine in autoimmune treatment. This review highlights the transformative potential of biodegradable and stimuli-responsive nanomaterials, presenting them as a promising strategy to advance precision medicine and improve patient outcomes in autoimmune disease management.

Citrullinated IGF2BP1 promotes rheumatoid synovial aggression via increasing the mRNA stability of SEMA3D

Protein citrullination modification plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and anti-citrullinated protein antibodies (ACPAs) are extensively employed for clinical diagnosis of RA. However, there remains limited understanding regarding specific citrullinated proteins and their implications in the progression of RA. In this study, we screen and verify insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) as a novel citrullinated protein with significantly elevated citrullinated level in RA. Autoantibodies against citrullinated IGF2BP1 are further detected in serum and synovial fluid samples from RA patients, which are positively correlated with erythrocyte sedimentation rate (ESR) and disease activity score 28 (DAS28). Transcriptomic sequencing and functional verification show that citrullination at the R167 site of IGF2BP1 promotes the proliferation, migration, and invasion of RA fibroblast-like synoviocytes (RA-FLSs) by improving the mRNA stability of Semaphorin 3D (SEMA3D). Experiments in collagen-induced arthritis (CIA) mice, the classical animal model of RA, show that IGF2BP1 R176K point mutation (Igf2bp1R167K/R167K) mice exert reduced inflammatory response, clinical scores, and joint destruction. At a molecular level, citrullination of IGF2BP1 promotes the stability of SEMA3D mRNA by promoting the interaction between IGF2BP1 and its cofactor ELAV-like protein 1 (ELAVL1), thereby promoting the invasiveness of RA-FLSs. In this study, a new citrullinated protein of IGF2BP1 is discovered, and the molecular mechanism of its citrullinated modification promoting the progression of RA disease is elucidated, which provides theoretical basis for the diagnosis and treatment of RA.

Updated Review for Guidelines for Cervical Cancer Screening in Immunosuppressed Women Without HIV Infection.

The purpose of this review was to examine new evidence since our 2019 guidelines for cervical cancer (CC) screening in non-HIV immunocompromised persons and to provide updated recommendations based on literature review and expert opinion. In addition, human papillomavirus (HPV) vaccine efficacy in these populations was reviewed. A literature search was performed similar to our previous publication but was conducted through March 2023. Risk of CC, squamous intraepithelial lesions, and HPV infection in those living with solid organ transplant (SOT), end-stage renal disease (ESRD), hematopoietic stem cell transplant (HSCT), and autoimmune diseases (AID), specifically systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) with addition of multiple sclerosis (MS) were researched. This update also summarizes data available on newer disease-modifying therapies (DMTs) including monoclonal antibodies (MABs). We then made recommendations for HPV vaccine administration, and screening using either general population guidelines or increased surveillance, the latter based on following current recommendations for women living with HIV. Additionally, the literature search included antibody response to HPV vaccines and recommendations for their administration for these same conditions. Based on the reviewed risks, evidence continued to support those persons living with SOT, ESRD, HSCT, and SLE, whether on immunosuppressant therapy or not, had an increased risk of HPV, squamous intraepithelial lesions, and CC whereas there was weak evidence that those persons with IBD, RA, and MS not on immunosuppressants were at risk. Data on persons using DMT/MAB were conflicting. Data showed that patients on certain immunosuppressants had lower antibody titers following HPV vaccination. There were no studies on HPV vaccine efficacy. Following US Center for Disease Control and Prevention HIV Cervical cancer screening (CCS) guidelines is recommended for the following: SOT, ESRD, HSCT, and SLE whether on immunosuppressants or not, and IBD, RA, and MS on immunosuppressants. Shared decision-making about increased surveillance for IBD and RA not on immunosuppressants and persons on any DMT or MAB is reasonable based on conflicting data. Human papillomavirus vaccination should not change the recommendations for increased CC surveillance. A 3-dose series of the HPV vaccine is recommended for all age-eligible patients starting at 9 years of age, with catch-up to 26 years of age. Vaccination from age 27 up to age 45 years per Advisory Committee on Immunization Practices guidelines should be considered in shared decision-making. When possible, HPV vaccine series should be initiated and completed before SOT or initiation of DMT/MAB. For HSCT, the vaccine series should be readministered along with other childhood vaccines.

Biosimilars in Focus: Evaluating Their Role Compared to Adalimumab in Clinical Practice

Introduction and Purpose: Adalimumab, a TNF-α inhibitor, is a cornerstone treatment for autoimmune and inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Despite its efficacy, the high cost of adalimumab (Humira®) limits accessibility. The emergence of biosimilars offers cost-effective alternatives with comparable efficacy, safety, and immunogenicity. This article reviews the role of adalimumab biosimilars, their clinical equivalence, and potential to address healthcare challenges. Materials and Methods: A comprehensive literature review was conducted to evaluate the structural, functional, and clinical parity of adalimumab biosimilars with the reference product. Key studies on pharmacokinetics, efficacy, safety, therapeutic drug monitoring (TDM), and real-world outcomes were analyzed. Results:Adalimumab biosimilars demonstrate equivalent pharmacokinetic profiles and clinical efficacy across conditions, with comparable remission rates and safety profiles. Innovations, such as citrate-free formulations and advanced delivery devices, enhance patient adherence. Biosimilars significantly reduce treatment costs, increasing accessibility, especially in resource-constrained settings. Challenges remain in patient acceptance and managing therapy transitions. Conclusion:Biosimilars are transformative in addressing the cost barrier of biologic therapies, maintaining therapeutic equivalence to adalimumab while expanding access globally. Enhanced TDM and patient-centered strategies are essential for optimizing outcomes and maximizing their adoption in clinical practice.

Introduction of c' g- Closed Sets in Nano Topological Spaces and Elimination of Prodromes in Rheumatoid Arthritis Disease Through Nano Topology

Introduction of c' g- Closed Sets in Nano Topological Spaces and Elimination of Prodromes in Rheumatoid Arthritis Disease Through Nano Topology

Coexisting rheumatoid arthritis and sickle cell disease: case series and literature review.

Rheumatoid arthritis (RA) is rarely reported among patients with sickle cell disease (SCD). RA treatment in these patients is believed to be more challenging due to fear of increasing the risk of infection and complications of SCD. We are reporting 7 patients with concurrent SCD and RA. The average age at the time of the diagnosis of RA was 33.3±12.6 years (ranging from 16 to 53 years), and most were women (5/7). Most of the patients were positive for rheumatoid factor (6/7) or anticyclic citrullinated peptide (6/7). Four patients were treated with hydroxyurea. The most used antirheumatic drugs were methotrexate (7/7), biologic agents (5/7), and prednisone (4/7). Two patients were in remission, four had low and one had high disease activity. Four patients (4/7) had avascular necrosis, two in the shoulders and two in the hip joints. Four patients had emergency visits or hospitalizations within one year of the diagnosis of RA, but none had blood transfusions, infections, or death. The start of antirheumatic medication was not associated with an increased risk of infection, blood transfusions, emergency visits, or hospitalizations, nor with a worsening of laboratory measures. The findings suggest that the treatment of RA in patients with SCD should follow the same strategy as in patients without SCD. However, treatment should be individualized according to the individual patient's risk of infection and SCD complications.

Current Status of Depression in Patients with Endometriosis and Rheumatoid Arthritis.

Endometriosis often causes chronic pain and fertility issues, exacerbating the risk of depression and complicating conditions like rheumatoid arthritis, which further impacts quality of life. This study aimed to explore the detection rate of depression in patients with endometriosis and rheumatoid arthritis by using different diagnostic criteria, and to analyze the occurrence and influencing factors. A total of 108 patients with endometriosis combined with rheumatoid arthritis in the First Hospital of Lanzhou University from July 2021 to July 2023 were selected as samples. The internationally accepted Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the new depression assessment tool Hamilton Depression Scale (HAMD), and the Self-rating Depression Scale (SDS) were used to detect the incidence of depression in patients with endometriosis and rheumatoid arthritis. On the basis of the DSM-5 results, patients with concurrent depression were categorized into the observation group, and those without depression were categorized into the control group. The patients' clinical data were collected, and the impact factors were analyzed through binary logistic regression. DSM-5 detected 20 patients with depression, with a detection rate of 18.52%. HAMD detected 21 patients with depression, with a detection rate of 19.44%. SDS detected 18 patients with depression, with a detection rate of 16.67%. The difference in the detection rate of depression in patients with endometriosis combined with rheumatoid arthritis among the three methods was not statistically significant (p = 0.865). Binary logistic regression analysis showed that dysmenorrhea (odds ratio (OR) = 3.589, p = 0.005), dyspareunia (OR = 2.964, p = 0.012), Visual Analog Scale score (OR = 2.545, p = 0.001), Disease Activity Score-28 score (OR = 3.828, p = 0.004), Pittsburgh Sleep Quality Index score (OR = 3.942, p = 0.004), and Health Assessment Questionnaire-Disability Index score (OR = 3.527, p = 0.008) were significant influencing factors for depression. DSM-5, HAMD, and SDS can be used to detect depression in patients with endometriosis and rheumatoid arthritis as effective tools for depression screening. Dysmenorrhea, dyspareunia, Visual Analog Scale (VAS), Rheumatoid arthritis disease activity (DAS28), Pittsburgh Sleep Quality Index (PSQI), and Health Assessment Questionnaire-Disability Index (HAQ-DI) are influencing factors of depression in these patients.

Expression profiles of miR-101-3p and miR-431-5p as potential diagnostic biomarkers for rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation of the synovial joints, leading to cartilage and bone destruction. This study aimed to evaluate the diagnostic utility of specific microRNAs (miRNAs) as potential biomarkers for RA. The study was conducted on 60 patients with RA disease along with 20 control participants. Comprehensive analysis of patient data, encompassing serological, hematological, and biochemical markers, revealed significantly elevated levels of miR-99b-5p, miR-101-3p, and miR-431-5p in RA patients compared to healthy controls. Among these, miR-101-3p demonstrated the highest diagnostic accuracy, with an area under the curve (AUC) of 0.873. These findings contribute to a deeper understanding of RA pathogenesis and suggest that miR-101-3p may serve as a valuable biomarker for early disease detection and potentially improved patient management. Further research is warranted to elucidate the precise mechanisms underlying miRNA involvement in RA and to explore their potential as therapeutic targets.

A Review of Connecting Bioinformatic Techniques to Rheumatoid Arthritis and its Associated Comorbidities.

Rheumatoid Arthritis (RA) is a progressive autoimmune condition inflicting serious threats to people's life and health by causing severe pain and joint destruction. It affects not only bones and joints but also causes comorbid conditions and shortens the lifetime. The interactions and synergistic effects of comorbid disease with RA are not yet well studied. Hence, understanding how these conditions will collectively affect the progression and outcome of RA is the current area of research. Identification of RA and comorbidities associated with target genes may uncover diagnosis and treatment methodologies. This review is to provide an overview of the interlinking approach of Rheumatoid Arthritis with its comorbid conditions and its systemic complications using bioinformatic techniques which would be useful to identify the genes and pathways that are in common for both RA and comorbid diseases. It would also emphasize the significance of bioinformatics in comparing the pathological features of RA and comorbid diseases. With the help of bioinformatics, valuable insights into the mechanism underlying Rheumatoid arthritis and comorbid diseases would be better understood.

Understanding Cardiovascular Events With JAK Inhibitors: Tofacitinib Reduces Synovial and Vascular Inflammation but not the Prothrombotic Effects of Inflammatory Cytokines on Endothelium.

Inflammation drives cardiovascular disease in rheumatoid arthritis (RA). Treatment with tofacitinib, a JAK1/JAK3 inhibitor, is associated with increased cardiovascular events in patients with RA. Here, we determined its effects on cytokine production during interactions between immune cells at the synovial and vascular levels and its impact on endothelial activation and coagulation during inflammation. Activated human peripheral blood mononuclear cells (PBMCs) were cocultured with RA synoviocytes or endothelial cells (ECs) mimicking the cellular interactions in synovium and vessels responsible for cytokine production. A dose-response of tofacitinib was tested on interferon γ, interleukin (IL) 17A, IL-10, IL-6, and IL-1β, and cytokine production was measured by enzyme-linked immunosorbent assay at 48 hours. Endothelial activation was induced with IL-17A and tumor necrosis factor (TNF) or on contact with PBMCs. Shortly after tofacitinib treatment, the expression of EC activation markers, specifically IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, and of coagulation, including tissue factor and thrombomodulin, was assessed by real-time polymerase chain reaction. Tofacitinib differentially inhibited production of IFNɣ, IL-17A, and IL-10 from PBMC cocultures with RA synoviocytes or ECs (all P < 0.001). In cocultures with ECs, tofacitinib reduced further IL-6 and IL-8 production (both P < 0.001). In ECs activated by TNF/IL-17A or indirectly via contact with activated PBMCs, tofacitinib decreased IL-6 upregulation but not that of IL-8, E-selectin, or tissue factor. Thrombomodulin was significantly decreased. VCAM-1 was greatly induced with a higher dose of tofacitinib in ECs incubated directly with added inflammatory cytokines (P < 0.05) or released by interaction with activated PBMCs (P < 0.001). Tofacitinib inhibits synovium and vascular inflammation but fails to prevent the prothrombotic effects of inflammatory cytokines on ECs.