Markers Of Rheumatoid Arthritis Research Articles

Circulating cell-free DNA as a potential biomarker for prediction of disease activity and prognosis among Egyptian rheumatoid arthritis patients.

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls (P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels (P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores (P-values <0.05) but did not correlate significantly with tenosynovitis scores (P-values >0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients (P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.

Natural killer cell activity and its relationship with disease activity in rheumatoid arthritis patients

The aim of this study was to explore the relationship between natural killer cell activity (NKA) and disease activity of rheumatoid arthritis (RA). We retrospectively reviewed 259 patients’ data including RA markers associated with disease activity and NKA measured by a blood NKA test. Patients were divided into two groups based on their NKA levels, a low NKA group (NKA < 100 pg/mL) and a high NKA group (NKA 100–250 pg/mL). The low NKA group exhibited heightened RA characteristics, including increased seropositivity, anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joints, visual analog scale (VAS), and TNF-α antagonist usage. A negative correlation was observed between NKA and RA severity metrics, including rheumatoid factor (RF), anti-CCP antibodies, ESR, C-reactive protein, tender and swollen joints, and VAS scores. Logistic regression analysis indicated that factors such as seropositivity, elevated RF and anti-CCP antibodies, increased tender and swollen joints, higher VAS scores, and the employment of biological agents were linked with higher chances of belonging to the lower NKA group. Comparable trends were found within the seropositive RA patient subset. Our findings highlight a significant link between diminished NKA levels and exacerbated RA symptoms.

14-3-3 Eta protein as a novel biomarker in early detection of uveitis in Egyptian juvenile idiopathic arthritis and rheumatoid arthritis patients: Diagnostic and prognostic value.

Juvenile Idiopathic Arthritis (JIA) and Rheumatoid arthritis (RA) are autoimmune chronic inflammatory disorders of undetermined cause. Uveitis is one of the commonest and most dangerous extra-articular manifestations of JIA and RA presenting chronic anterior uveitis with non-specific biomarkers for its early detection. We evaluated the role of serum 14-3-3 Eta protein to assess its potential role as a novel biomarker for the early detection of uveitis in Egyptian JIA and RA patients as well as its correlation with disease activity. A case-control study included three patient groups: group I includes 42 JIA patients, group II includes 42 RA patients, and an equal number of apparently healthy individuals matched in sex and age for each group of patients as controls, recruited from the rheumatology outpatient clinic. All participants were subjected to clinical examination, laboratory investigations with assessment of serum levels of 14-3-3 Eta protein, and ophthalmologic investigations to assess disease activity, eye affection, and its relation to 14-3-3 Eta protein level, and other disease variables among those patients. a statistically significant difference was estimated between the two patients' groups and controls regarding 14-3-3 Eta protein level. 14-3-3 Eta protein has a significant positive correlation with disease activity in JIA and RA patients. Also, RA patients with clinical uveitis had higher levels of the 14-3-3 Eta protein, while there were no significant differences among JIA patients with or without uveitis. 14-3-3 Eta protein is a potential diagnostic biomarker in early detection of uveitis in RA patients, as it is higher in patients versus controls especially those with uveitis with a cut-off point 57.5, at which patients must have a thorough eye examination to receive early intervention and, to prevent complications, while it doesn't have the same role in JIA patients. 14-3-3 Eta protein is a potential diagnostic and prognostic marker for JIA and RA being correlated with disease activity.

The reliability and validity of superb microvascular imaging as a potential disease activity marker in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown aetiology, that causes progressive and destructive inflammation in the joints. Superb microvascular imaging (SMI), a new ultrasound technique that allows visualizing slow blood flow in synovitis. This study aimed to report the clinical value and utility of the SMI technique and its grading for monitoring RA by determining the correlation with clinical disease activity scores (DAS 28) and power Doppler ultrasound (PDUS). All RA patients with clinically apparent synovitis were assessed using DAS 28. Synovitis were investigated with PDUS and SMI and each joint was graded semiquantitatively. All assessments were carried out at baseline and repeated at least 4-month follow-up. Correlations between scores were investigated using Spearman's correlation. Sixty RA patients with 552 affected joints were recruited. Clinical and sonographic scores were significantly improved at follow-up (p<0.001). SMI showed significantly more joint count and flow signal scores than clinical examination and PDUS. Moderate correlations were found between SMI score and clinical scores (p<0.001,0.586 for SMI score vs DAS 28-CRP, p=0.001,0.432 for SMI vs DAS 28-ESR). There were also stronger correlations between SMI score and PDUS score at both baseline and follow-up (p<0.001, r = 0.817, 0.842 respectively). SMI provides greater utility and ability to detect synovial vascularity and monitor disease activity than PDUS. A new activity scoring system based on SMI and clinical objective findings is required to improve reliability and validity.

Comprehensive analysis of glycoprotein profiles and their association with cardiovascular disease-related microRNAs in rheumatoid arthritis, metabolic disorders, and controls

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint pain and disability. The connection between RA and cardiovascular (CV) disease is still being studied. This research aims to explore the relationship between CV-related microRNAs, inflammation, and glycosylated proteins to understand RA’s inflammatory pathophysiology concerning CV disease. The study included 219 RA patients, 82 with metabolic disorders, and 64 controls. Clinical evaluations and blood samples were collected. Quantification of microRNAs (Let7a, 24, 96, 103, 125a, 125b, 132, 146, 191, 223, 425, 451) and measurement of glycoproteins (GlycA, GlycB, GlycF) using proton nuclear magnetic resonance (1 H-NMR) were performed. Multivariate linear models were applied. RA patients showed higher glycoprotein levels than those with metabolic disorders and controls. Significant associations between miRNAs 24, 451, Let7a and glycoprotein levels were found in RA patients, particularly in women. Glycoprotein levels were positively correlated with inflammatory markers, highlighting their role in indicating RA severity. This study highlights elevated glycoprotein levels in RA patients, indicating a severe inflammatory pattern. Moreover, glycoproteins were highly associated with CV-disease-related miRNAs, indicating that glycoproteins are involved in both inflammation and CV disease. Finally, the inflammatory profile of glycoproteins was validated as they were highly associated with inflammatory markers of RA.

Improved vascular health linked to increased physical activity levels and reduced sedentary behavior in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by deteriorated vascular health and increased cardiovascular risk. Physical activity (PA) is recommended for cardiovascular management in RA, but evidence on the associations between objectively measured PA and vascular health markers in RA is limited. In this cross-sectional study, 82 postmenopausal women with RA (62 ± 7 yr) undertook ultrasound assessments of vascular function and structure, including brachial and superficial femoral artery (BA and SFA) flow-mediated dilation; baseline and post-hyperemia peak diameters; and carotid intima-media thickness. Participants also performed a 7-day accelerometer-based assessment of PA and sedentary behavior (SB). Fitted regression models controlled for age, body mass index, and disease activity were conducted to examine associations between vascular and PA outcomes. Regression analyses revealed that prolonged SB (bouts >60 min) and total sedentary time were inversely associated with both baseline and peak BA diameters, with each additional hour of SB resulting in decreases of 0.08-0.1 mm in these diameters (P ≤ 0.01). Total sedentary time also showed similar negative associations with peak SFA diameters (β = -0.14 [-0.24 to -0.05], P < 0.01). Conversely, light-intensity PA and stepping time were positively associated with both baseline and peak BA diameters, with each additional hour increasing these diameters by 0.10-0.24 mm (P ≤ 0.02). Finally, standing time was positively associated with SFA peak diameter (β = 0.11 [0.01-0.20], P = 0.02). No associations were found between moderate-to-vigorous PA and vascular outcomes. In conclusion, in patients with RA, SB was negatively, whereas light PA was positively, associated with BA and SFA diameters. These findings suggest that reducing SB and increasing PA, even at light intensities, may improve vascular health in RA.NEW & NOTEWORTHY This was the first study to investigate associations between objectively measured physical activity and markers of vascular health in rheumatoid arthritis (RA). The findings suggest that reducing sedentary behavior and increasing light or total physical activity are associated with improved vascular outcomes in RA. These results support further investigation into interventions aimed at reducing sedentary time and replacing with any type of physical activity as a potential strategy for improving cardiovascular outcomes in individuals with RA.

Cardiac remodeling in rheumatoid arthritis: assessing the influence of anti-CCP and rheumatoid factor

Abstract Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF), markers of Rheumatoid Arthritis (RA) activity, are associated with adverse cardiovascular outcomes, suggesting a potential link between RA and cardiac remodeling. Purpose Our study aimed to explore the correlation between antibody levels (anti-CCP and RF) and left ventricular (LV) remodeling in RA patients without known heart disease. Additionally, it sought to identify other disease-related factors that correlate with LV remodeling. Methods A cross-sectional study of 124 RA patients aged ≥ 18 years, classified per the 2010 ACR/EULAR criteria, collected blood samples for CRP, and antibody levels (RF ≥ 20 IU/ml and anti-CCP ≥ 5 IU/ml via ELISA). Transthoracic echocardiography (TTE) was conducted using a linear method in a long-axis parasternal 2D window. Sixty-two patients exhibited LV remodeling and were matched with 62 patients without it. Echocardiographic variables included were those to calculate the relative wall thickness (RWT, cut-off value 0.42) and left ventricular mass index (LVMI, cut-off values of 43-95 g/m2 in women and 49-115 g/m2 in men) along with left ventricular end diastolic (LVIDd), and systolic volumes (LVIDs), and left ventricular ejection fraction (LVEF). Statistical analyses employed the Chi-square test, Student's t-test, or Mann-Whitney U test as applicable, with correlations assessed using Spearman's rho, an analysis was conducted on the area under the curve (AUC) and a significance level of p ≤ 0.05. Results The most common type of LV alteration in our study was concentric remodeling (74.2%). A statistically significant difference was observed in the levels of Anti-CCP titers 193.85 IU/ml (p &amp;lt; .001), RF IgM 200.00 IU/ml (p &amp;lt; .001) and IgA 185.5 IU/ml (p &amp;lt; .001) in patients with LV remodeling. Anti-CCP and RF IgA antibody levels exhibited a moderate correlation with the presence of LV remodeling, with rho 0.387 (p &amp;lt; .001) and rho 0.344 (p &amp;lt; .001), respectively. The RWT showed a moderate correlation with anti-CCP titers with rho 0.298 (p .001). AUC analysis anti-CCP titers demonstrated better diagnostic performance for the existence of cardiac remodeling (0.722, 95% CI 0.628-0.816, p &amp;lt; .001), RF IgA (0.696, 95% CI 0.602-790, p &amp;lt; .001) and IgM (0.650, 95% CI 0.563-755, p .002). Conclusion In summary, among RA patients without heart failure (HF), LV remodeling and elevated RWT correlate with antibody levels independently of traditional cardiovascular risk factors. Patients with altered LV geometry exhibit higher antibody titers, highlighting the need for RA-related biomarkers that correlate with changes in LV structure and function Recognizing association between autoimmunity and HF development holds significant implications for both prevention and treatment strategies in RA patients.

What Could Lead to the Production of Anti-Rheumatoid Antibodies in Patients with Brucellosis Spondylodiscitis: Possible Causes.

High titers of specific antibodies to cyclic citrulline peptide (ACCP) are often present in the serum of patients with rheumatoid arthritis (RA) and, together with rheumatoid factor (RF), are a diagnostic marker of RA. Brucellosis is a zoonotic infection in which osteoarticular involvement occurs in 10-85% of patients. RF in brucellosis patients is significantly higher than in healthy people. We presented 2 cases of brucellosis spondylodiscitis with positive results for RF and ACCP, which aroused great interest among the rheumatologists of our center. Both patients described were men (27 and 60 years old) with arthritis, back pain, and high levels of rheumatoid arthritis-specific antibodies. These patients were suspected of having tuberculous spondylitis, but the tuberculous process was excluded using specific tests. During antibacterial therapy, there is a dynamic decrease in antirheumatoid antibodies. X-rays of the hand joints revealed no signs of erosive arthritis. All cases of arthritis, spondylitis, and spondylodiscitis in endemic areas require careful analysis and comparison of patients' clinical and laboratory-instrumental data to prevent misdiagnosis. With brucellosis infection, against the background of adequate antibacterial therapy, inflammation of the joints and spine is reversible.

B-078 Serodiagnosis of Rheumatoid Arthritis Using the New Accentis Chemiluminescence Immunoassay Platform for Anti-CCP Antibody Detection

Abstract Background Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and the most frequent chronic inflammatory arthropathy. Reliable diagnosis at the earliest possible stage is indispensable to keep the disease under control with suitable therapy and to prevent irreversible joint damage. Autoantibodies against cyclic citrullinated peptides (CCP) are a highly specific marker for RA with relevance for (differential) diagnosis, prediction and prognosis. In this study, we investigated the clinical and analytical performance of a newly developed anti-CCP chemiluminescence immunoassay (ChLIA) system. Methods Serum samples from 170 patients with clinically confirmed RA and from a control panel of 274 patients with other diseases were analyzed using the EUROIMMUN Anti-CCP ChLIA (IgG), which was processed on the fully automated random-access system Accentis (EUROIMMUN). The results were compared with those obtained with the EUROIMMUN Anti-CCP ELISA (IgG) with regard to sensitivity, specificity and inter-assay concordance. Results The ChLIA achieved a sensitivity of 71.2% (121/170) and a specificity of 97.4% (267/274), while the ELISA was less sensitive (67.5%, 114/170) and specific (96.4%, 264/274). The qualitative results showed positive and negative agreement rates between the two assays of 92.7% (115/124) and 95.9% (307/320), respectively, resulting in 95.0% (422/444) overall agreement and a kappa score (0.878) indicating near perfect agreement. Conclusions The new Accentis ChLIA showed improved sensitivity and specificity for the detection of anti-CCP antibodies compared to the corresponding ELISA. Given the enhanced clinical performance and the practical benefits of using a random-access system, this ChLIA platform can effectively support the diagnosis of RA.

Microarchitectural analysis of the metacarpophalangeal joint using HR-pQCT in patients with rheumatoid arthritis: A comparison with healthy controls

ObjectiveTo investigate which joint microarchitectural parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) serve as imaging markers for rheumatoid arthritis (RA). MethodsThe second and third metacarpophalangeal (MCP) joints of 50 patients with RA and 50 healthy controls (HCs) (aged 50–79 years, all females) were scanned using a HR-pQCT. Joint space, trabecular bone microarchitecture, and erosion were measured and compared between RA patients and HCs. ResultsThere were no differences in joint space parameters between RA patients and HCs.For bone microarchitecture, RA patients had lower trabecular bone mineral density (127 vs. 167 mg/cm3), thinner trabecular thickness (0.20 vs. 0.21 mm), fewer trabecular number (1.49 vs. 1.55 /mm), more rod-like structure (1.68 vs. 1.23), and poorer trabecular connectivity (4.51 vs. 5.72 /mm3) than HCs.Regarding erosion, RA patients had a higher number of erosions per joint (36/100 vs. 18/100), larger volume (4.62 vs. 1.89 mm3), and longer width (2.40 vs. 1.82 mm) and longer length (2.34 vs. 1.64 mm) than HCs.Most of the erosions in HCs were <5 mm3 in volume (95 %) and located on the radial side (85 %). When erosions <5 mm3 were compared between RA patients and HCs, there were no differences in their location or morphology. ConclusionsDeterioration of bone microarchitecture and existences of erosions >5 mm3 in the MCP joints are sensitive imaging markers of RA. Erosions <5 mm3 in RA patients may include not only early pathological erosion but also physiological erosion because even HCs can have erosions <5 mm3.

Analysis and identification of ferroptosis-related diagnostic markers in rheumatoid arthritis

Background Rheumatoid arthritis (RA) is an autoimmune, inflammatory joint disease. There is growing evidence that ferroptosis is involved in the pathogenesis of RA. This study aimed to search for diagnostic markers of ferroptosis in RA and to analyse the potential mechanisms and clinical value. Materials and methods RA-associated datasets were used from the publicly available GEO database. Three methods of machine learning were applied to screen biomarkers. The diagnostic efficacy of the results was also verified by receiver operating characteristic (ROC) curve, external dataset, qRT-PCR and Western blot. Enrichment analysis was performed in this process, while protein–protein interaction (PPI) analysis and immune infiltration correlation analysis were performed using biomarkers, and competing endogenous RNA (ceRNA) networks were constructed to search for prospective therapeutic targets. Results MMP13 and GABARAPL1 can be used as ferroptosis diagnostic genes in RA. The ROC curve and PPI result demonstrated that MMP13 and GABARAPL1 had an excellent diagnostic value. The results of signature genes in the external dataset, qRT-PCR and Western blot further confirm our findings. The enrichment analysis showed that p53, MAPK and NOD-like receptor signalling pathways may be involved in the process of ferroptosis in RA. In addition, two ferroptosis diagnostic genes in RA participate in the occurrence of ferroptosis in RA via oxidative stress, metabolism and immune response. Immune infiltration analysis showed that RA extensively infiltrated B cells, T cells, macrophages and other immune cells. Persistent immune activation may be an essential reason for the progression of ferroptosis in RA. We also obtained five potential therapeutic agents for RA and some long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) regulating ferroptosis diagnostic genes. Conclusions Our study suggests that MMP13 and GABARAPL1, which are closely linked with oxidative stress and immunological modulation, can be used as ferroptosis-related potential diagnostic markers in RA and provide new clues regarding the diagnostic and therapeutic targets of ferroptosis in RA.

Decreased Serum CTRP3 level was associated with connective tissue diseases

ObjectiveComplement C1q tumor necrosis factor-related protein 3 (CTRP3) and 9 (CTRP9) are two of the most extensively studied adipokines, known for their diverse biological functions. However, it remains unclear whether serum levels of CTRP3 or CTRP9 are associated with connective tissue diseases (CTD). MethodsSerum CTRP3 and CTRP9 levels were measured by enzyme-linked immune sorbent assay (ELISA) and analyzed in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), ankylosing spondylitis (AS), undifferentiated connective tissue disease (UCTD), as well as in healthy controls (HCs). ResultsSerum CTRP3 levels were all significantly lower in patients with RA, SLE, pSS and AS compared with HCs. However, there were no significant differences in serum CTRP9 levels between patients with RA, SLE, pSS, or AS and HCs. In pSS patients, CTRP3 showed a weak correlation with blood glucose, creatinine, and urine acid in pSS patients, while no correlations were observed between serum CTRP3 levels and clinical or laboratory indices in RA, SLE or AS patients. Stable associations between CTRP3 and RA, SLE, pSS and AS were evaluated using multivariate logistics regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluated CTRP3 as a marker for RA, SLE, pSS and AS, yielding area under curve (AUC) values of 0.691, 0.727, 0.658 and 0.694, respectively. ConclusionDecreased serum CTRP3 levels were associated with RA, SLE, pSS and AS.

Extensive study of CCN4, VCAM-1, MMP-3, and GM-CSF as reliable markers for disease activity in rheumatoid arthritis

BackgroundThe involvement of Wnt-1-induced secreted protein-1 (WISP1/CCN4) in several inflammatory reaction has recently been proposed. Nevertheless, this protein's involvement in rheumatoid arthritis (RA) remains debated. Associations between poorly diagnosed RA and several classical markers derived from demography and biochemistry have been reported. AimWe sought to investigate the reliability and effectiveness of serum concentrations of CCN4, vascular cell adhesion molecule-1 (VCAM-1), matrix melloprotenase-3 (MMP-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in monitoring and predicting RA and bone damage, and their correlation with RA disease course. MethodsThe study analyzed 128 patients with RA, comprising 68 newly diagnosed and 60 previously diagnosed patients, as well as 60 controls. Biomarker levels were measured with enzyme linked immuno-sorbent assays. Routine laboratory parameters such as serological, clinical, biochemical, and hematological parameters were additionally measured. Demography, anthropometry, and clinical symptom data were collected through interviews and a questionnaire. The joint disease activity score 28 (DAS28) was used to determine disease activity. ResultsConcentrations of four biomarkers were significantly higher in the RA group than the healthy controls. Elevated biomarker concentrations were also observed in patients with high, rather than moderate or low, DAS28-ESR activity status, except for monocyte count, hematocrit (%), and urea level. Furthermore, CCN4 level positively correlated with VCAM-1, MMP-3, and GM-CSF levels, DA-S28-CRP and DAS28-ESR. The levels of three predictive markers, CCN4, VCAM-1, and MMP-3, were elevated in non-treated patients, whereas GM-CSF level showed no difference. The highest area under the curve was 73.3% for CCN4, with 93.3% sensitivity and 64.7% specificity. ConclusionOur data suggest that CCN4 can be reliably used to indicate activity and therapeutic response associated with RA, thus facilitating earlier RA diagnosis.

Rheumatoid meningitis in the absence of rheumatoid arthritis: 2 cases

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA) that has been increasingly recognized by neurologists. However, the diversity of its clinical manifestations makes its diagnosis difficult. RM does not have a unified diagnostic standard, and its link with RA needs to be studied further. Here we report two cases of RM without a history of RA. The first patient, an 80-year-old woman, presented with sudden unilateral limb weakness, with brain MR showing abnormal signals in the leptomeningeal of the right frontal parietal. Subarachnoid hemorrhage was excluded after imaging examination, and infectious meningitis was ruled out after cerebrospinal fluid (CSF) examination. The patient was diagnosed as having RM, she had increased levels of CCP and AKA, the markers of RA, but no history of the disease or other clinical manifestations of it. Another case, a 65-year-old man, was hospitalized with Bell’s palsy. We found that he had intracranial imaging changes highly consistent with those characteristic of RM during his routine examination. Except for the left peripheral facial palsy, the patient had no other neurological signs or symptoms and no RA history. After a careful physical examination, we found no joint or other manifestations or serological abnormalities consistent with RA (RF, CCP, AKA, etc.). However, after excluding infection meningitis and considering the patient’s unique imaging results, we diagnosed him as having RM. We report these two cases as references for clinical diagnosis and treatment of RM, providing a discussion of our rationale.

Role of CXCL-10 as a Biomarker for Rheumatoid Arthritis

Abstract Background CXCL-10 has been detected within sera, synovial fluid, and synovial tissue in patients with RA and identified as a pro-inflammatory chemokine that mediate leukocyte trafficking and modulate innate and adaptive immune responses. It plays a critical role in the inflammatory response and is involved in several biological processes. Objective To evaluate the predicative significance of chemokine CXCL10 in rheumatoid arthritis (RA) and to focus on its relation to disease activity. Patients and Methods A case control study included 30 patients; were diagnosed with RA, and 30 healthy controls. Clinical examination was done for all patients. Measurement of serum CXCL10 level was done by ELISA, while assessment of disease activity in patients was done using disease activity score (DAS-28). Serum levels of CXCL10 were significantly higher in RA patients than controls. Results Serum level of CXCL-10 was ranging from 349–1380 pg/ml with a mean of 784.6 ± 152.2 in RA patients, which was very high level compared to control group the serum level was ranging from 137 – 476.8 pg/ml with a mean of 338.1 ± 125.5. The difference was statistically highly significant (p &amp;lt; 0.001). AUC for CXCL-10 was 0.951 and the 95% CI was ≤ 1. The cutoff point of CXCL-10 was 450 pg/mL were able to differentiate between RA patients and control group. Most of RA patients (70%) were on methotrexate with dose ranged from 12.5–25 mg per week. Thirty-five (58.3%) patients were on steroids with dose 5-20 mg per day. Comparison of CXCL-10 levels in patients with different grades of disease activity had a statistically significant difference between different grades. Conclusion Our study supports the critical role of CXCL10 in the RA inflammatory cascade. The correlation of CXCL10 with clinical disease activity suggests that CXCL10 plays a central role in RA inflammation and may serve as a disease activity marker in RA. CXCL10 has a significant role as a biomarker for prediction of RA.

Identification of novel biomarker hsa_circ_0003914 for rheumatoid arthritis from plasma exosomes

Rheumatoid arthritis (RA) is a complex autoimmune disease featuring invasive and infiltrative fibroblast-like synoviocytes (FLS) that lead to joint damage. While current RA pathological mechanisms remain incompletely defined, exosomes have been implicated as having the potential to drive disease progression due to their ability to deliver different types of biomolecules to tissues effected by RA. One potentially disease exacerbating molecule type found in exosomes are Circular RNAs (circRNAs), which are highly stable and have been previously implicated in RA pathogenesis. Here, we examine hsa_circ_0003914, a circRNA found in exosomes located in blood plasma, for a role in RA. Plasma exosomes were isolated and injected into collagen-induced arthritis (CIA) mice, followed by functional experiments to analyze the influence of exosomes on FLS formation. Sequencing revealed the presence of hsa_circ_0003914 in exosomes, so we examined its association with clinical markers in RA. Finally, the role for hsa_circ_0003914 in RA was directly confirmed through in vivo and in vitro experiments. We found that plasma exosomes isolated from RA patients could aggravate the disease of CIA mice, compared to exosomes isolated from healthy control patients. Hsa_circ_0003914 was highly enriched in the exosomes of RA patients. Mechanistically, Hsa_circ_0003914 promoted abnormal cell proliferation, migration, invasion and stimulated the secretion of inflammatory cytokines in FLSs through targeting NF-κB/p65 signaling pathway. Interestingly, knockdown of hsa_circ_0003914 rescued disease phenotypes in CIA mice. Taken together, these data implicate hsa_circ_0003914 as a potential therapeutic target for the prevention and management of RA.

Analysis of potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression immunologic indicators

ObjectiveDepression can impact the severity of rheumatoid arthritis (RA). This study aimed to investigate the relationship between Th1, Th2, Th17, Treg cell subsets, and their associated cytokines (e.g., IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α), and the occurrence of RA both with and without comorbid depression. The objective is to identify potential biological markers, therapeutic targets, and the therapeutic effects of RA with comorbid depression. Results53 RA patients,46 RA with comorbid depression patients and 51 healthy subjects were included in the RA,RD and HC group from August 2021 and October 2022. Among RA patients, 46.46 % were comorbid with depression. IL-6 concentrations were significantly higher in RD group than in RA group.Comparison between the HC and RA and RD groups revealed that Th1 %, Th17 %, Th1, Th17, Th1/Th2, Th17/Treg and Th1/Treg were significantly higher in the RA and RD groups, and conversely, Th2 %, Treg%, Th2 and Treg were significantly lower than in the HC group.The RA group compared to the RD group found that Th17 %, Th17 and Th17/Treg were significantly higher in the RD group than in the RA group, however, Th1 %, Treg and Th2/Treg were significantly lower than in the RA group. The total HAMD score had a medium strength positive correlation with IL-6. ConclusionThese findings suggest that elevated the autoimmunity status was overactivated in RA with or without depression activates patients, IL-6 may be a predictor of the severity of RA with comorbid depression, IL-6 concentrations and an imbalance in the Th17/Treg may underlie the comorbidity of RA and depression, offering potential targets for therapeutic intervention, prompting further evaluation of the role of indirect inflammatory markers in RA with comorbid depression, highlighting the need for additional research to clarify the complex relationship between inflammation and psychological health.

Associations between type 1 diabetes and autoimmune skin diseases: Mendelian randomization analysis

BackgroundType 1 diabetes mellitus (T1DM) may be associated with various autoimmune diseases, but the causal relationship between T1DM and autoimmune skin diseases is not yet clear. MethodsThe summary statistical data on T1DM and nine autoimmune skin diseases in European populations were extracted for mendelian randomization (MR) analysis. Subsequently, the analysis was replicated in East Asian populations. In the MR estimation, inverse variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were utilized. Outliers were excluded using MR-PRESSO, and horizontal pleiotropy was assessed with MR-Egger. Additionally, a multivariable MR analysis was conducted to investigate whether T1DM has an independent effect on autoimmune skin diseases after adjusting for potential confounders. ResultsIn Europe, the MR estimated based on IVW method indicated a causal association between genetically determined T1DM and systemic lupus erythematosus (SLE) (OR = 1.38, 95%CI: 1.26−1.50, p＜0.01), rheumatoid arthritis (RA) (OR = 1.15, 95%CI: 1.05−1.25, p＜0.01), as well as multiple sclerosis (MS) (OR = 1.17, 95%CI: 1.01−1.36, p = 0.04), but there is no association between T1DM and atopic dermatitis (AD), vitiligo, lichen planus (LP), hidradenitis suppurativa (HS), alopecia areata (AA) and systemic sclerosis (SS). After adjusting for time spent watching television, body mass index, type 2 diabetes mellitus, and body fat percentage, we found a causal relationship between T1DM and SLE (OR = 1.29, 95%CI: 1.16–1.44, p < 0.01), RA (OR = 1.28, 95%CI: 1.20–1.38 p < 0.01) and MS (OR = 1.11, 95%CI: 1.04–1.18, p < 0.01). Then, no genetic causal association was found between TIDM and SLE, and AD in East Asia. These results didn't exhibit horizontal pleiotropy, and “leave-one-out” analysis demonstrated result stability. ConclusionOur MR research indicates a causal relationship between T1DM and SLE, RA, and MS in Europe. However, no causal relationship between T1DM and SLE has been observed in East Asia. Therefore, it is important to regularly monitor relevant immunological markers of SLE, RA, and MS in T1DM patients and take preventive measures.

WITHDRAWN: Efficacy of diets with specific compositions to reduce the symptoms of immune-mediated diseases. Narrative review

IntroductionDiet is considered a possible cofactor that participates in the inflammatory cascade and influences at the molecular level, microbiota, and intestinal permeability, affecting the immune system, and potentially causing dysregulation of intestinal homeostasis, inflammation, food intolerance, or food allergy. This study aimed to review the evidence on the effects of specific diet composition on the symptoms of some immune-mediated diseases -rheumatic diseases, multiple sclerosis, inflammatory bowel disease, and psoriasis-. MethodsWe conducted a narrative review of meta-analyses, and Cochrane systematic reviews, on PubMed, EMBASE, and Google Scholar, from inception to July 2023. The methodological quality of meta-analyses was assessed using AMSTAR 2 rating. ResultsEight meta-analyses showing the level of evidence for specific diets in IMD symptoms were selected and evaluated. A tendency to the reduction in pain, fatigue, and quality of life in the studied IMDs, and to improve inflammatory markers in rheumatoid arthritis with diets reducing inflammatory foods, and no differences were observed for other outcome measures, with a very low level of evidence. ConclusionsThis review provides clarity on the weaknesses of clinical trials and meta-analyses on diet, updates the global evidence on diet to improve immune-mediated disease symptoms, and analyzes the influence of dietary mechanisms. Likewise, it shows the beneficial effects of diets reducing inflammatory foods in decreasing the symptoms of immune-mediated diseases, however, the included studies had a very low level of evidence. The difficulty in obtaining high-level evidence is clear in diet studies, and this can delay the application of the results.

Association between serum antinuclear antibody and rheumatoid arthritis.

The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case-control study. Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis. A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively. There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.