Biomarkers For Rheumatoid Arthritis Research Articles

Circulatory age-associated B cells: Their distinct transcriptomic characteristics and clinical significance in drug-naïve patients with rheumatoid arthritis.

Age-associated B cells (ABCs) have been implicated in the pathogenesis of autoimmune diseases. However, the global gene expression and clinical significance of circulatory ABCs in rheumatoid arthritis (RA) remain poorly understood. Here, single-cell RNA sequencing identified nine B cell subsets in peripheral blood of RA patients, including ABCs. Increased phagocytosis and antigen presentation were functionally enriched by the genes expressed differentially in ABCs. Network analysis and in vitro experiments demonstrated SYK as a key regulator defining the myeloid-like phenotypes in ABCs. Flow cytometry showed that the proportion of ABCs correlated with RA activity and serum tumor necrosis factor-alpha level. Notably, ABCs above a cutoff threshold specifically distinguished RA from healthy controls and indicated higher disease activity. This study highlights the myeloid characteristics of circulatory ABCs regulated by SYK in RA. Increased ABCs may reflect disease activity and could serve as a potential biomarker in RA.

Disclosing the impact of metformin and methotrexate in adjuvant arthritis in female rats: molecular docking and biochemical insights on visfatin.

Rheumatoid arthritis (RA) is one of the most common systemic autoimmune inflammatory diseases, with a progressive etiology that results in serious complications and a higher chance of early death. Visfatin, an adipokine, is correlated with disease pathologic features and becomes a key biomarker and therapeutic target for RA. This study aimed to evaluate the anti-arthritic activity of metformin (an antidiabetic drug with anti-inflammatory activities) and methotrexate (the first choice for disease-modifying antirheumatic drugs in RA, with diverse adverse effects) in complete Freund's adjuvant (CFA)-induced arthritis in female rats. Treatment outcomes were assessed using arthritis severity, serum levels of inflammatory markers, and pro-inflammatory adipokine (visfatin). In addition to radiological and histopathological examination, and docking analysis. Results showed that Met, MTX, and Met/MTX significantly (p ≤ 0.05) lowered paw swelling and arthritic score, as well as attenuated serum levels of rheumatoid factor (RF), C-reactive protein (CRP), and visfatin. The combined treatment gives the best results. The previously mentioned findings were further confirmed through radiological and histopathological examinations. In conclusion, the co-administration of metformin could potentiate the anti-arthritic activity of methotrexate, providing a medical strategy for arthritis management.

One Step Visual Homogeneous Immunoassay of a Rheumatoid Arthritis Biomarker in Serum via Target-Regulated Steric Hindrance and Competitive Recognition.

Homogeneous analysis techniques offer several advantages as alternatives to heterogeneous immunoassays, such as simplicity and rapidity. In this study, a visual homogeneous immunoassay without a labeling process was developed based on target-induced steric hindrance to regulate competitive recognition mechanism. Specifically, as the analyte concentration varies, the change of microenvironment based on steric hindrance could affect the recognition of Cu2+ by signal probes. Herein, taking anticyclic citrullinated peptide antibody (anti-CCP) as an example, the method was verified. Cu2+ can bind to histidine (His), as well as signal probes. Cyclic citrullinated peptide containing His was served as the capture antigen, and the fluorescence of both CdTe quantum dots and calcein can be quenched by Cu2+. Then, this quenching effect can be regulated by the change of steric hindrance, so that anti-CCP analysis can be realized. The limit of detection of anti-CCP was as low as 0.002 and 0.01 U/mL in fluorescence mode and red, green, and blue (RGB) mode, respectively. Furthermore, clinical practicality was validated through 46 clinical samples, including rheumatoid arthritis patients (n = 28) and healthy donors (n = 18), with the assay demonstrating a sensitivity and specificity of 96.4% and 88.9%, respectively. Indeed, the results were consistent with those of clinical electrochemiluminescence immunoassays and digital radiography images. Overall, this method shows great potential for clinical application and offers a universal template for a label-free homogeneous immunoassay.

Regulation of reactive oxygen species and the role of mitochondrial apoptotic-related genes in rheumatoid arthritis

Previous research suggests mitochondrial apoptosis alleviates rheumatoid arthritis (RA), but the role of mitochondrial apoptosis-related genes (MARGs) is unclear. Urgent exploration of RA-related mitochondrial apoptosis biomarkers is needed. Gene Expression Ontology (GEO)-derived RA datasets were used to identify differentially expressed genes (DEGs) compared to normal controls, intersected with MARGs to obtain differentially expressed mitochondrial apoptosis-related genes (DE-MARGs). Three ML algorithms screened diagnostic biomarkers. A nomogram was built and validated by receiver operating characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA), regulatory network, and drug prediction explored biomarker mechanisms. Finally, key cells analysis included clustering, type annotation, pseudo-temporal study, and interaction, focusing on validated biomarker expression in those cells. A total of 147 DE-MARGs linked to energy & ROS metabolism were identified. Four validated biomarkers (MRPS10, EEF2, HSPA9, TUFM) formed a new RA diagnostic model. Moreover, GSEA linked them to oxidative phosphorylation. YY1 regulates EEF2, HSPA9, MRPS10; FOXO3 regulates EEF2, TUFM. Drugs like Nonoxynol-9, Nedocromil, Gadobutrol target these biomarkers. In addition, biomarkers are expressed in plasmablasts, with CD74 as a key receptor binding multiple ligands. RA biomarkers (MRPS10, EEF2, HSPA9, TUFM) linked to energy & ROS, progression tied to AMPK/mTOR, CD74-MIF crucial. Study advances RA pathogenesis knowledge, supporting clinical diagnosis.

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.

Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure

Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure

Multi-omic Biomarkers Distinguish Rheumatoid Arthritis in Discordant Monozygotic Twins.

Although genetic factors have been identified in the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other features contribute to disease development. Further, the relative contribution of such non-genetic elements in identical twins have not been characterized. Here, we aimed to measure differentiating host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multi-omics approach. Eight pairs of MZ twins discordant for RA (n=16) were enrolled. Gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and other plasma proteins were measured in both plasma and feces. Levels of short and medium-chain fatty acids from serum and feces were quantified using gas chromatography mass spectrometry (GC-MS). While overall microbiome diversity and composition did not significantly differ between twins, we observed a decrease in Blautia faecis in affected twins. Affected twins had higher concentrations of both fecal and plasma citrullinated and non-citrullinated autoantibodies, as well as significantly lower concentrations of fecal butyrate and propionate. Multi-omics biomarkers differentiate MZ twins discordant for RA. Blautia faecis , which is associated with reduced inflammatory cytokine expression, was decreased in RA twins. Similarly, short-chain fatty acids, known to have immune modulatory effects, were decreased in affected twins, suggesting further bi-directional interactions between inflammation at the gut barrier and disease state. If confirmed in other cohorts, exhaustive multi-omics approaches may improve our understanding of RA pathogenesis and potentially contribute to novel diagnostics and co-adjuvant therapies.

MicroRNAs as Biomarker in Rheumatoid Arthritis: Pathogenesis to Clinical Relevance.

MicroRNAs (miRNAs) have emerged as intricate players in rheumatoid arthritis (RA), holding promise as discerning biomarkers for diagnostic and prognostic purposes. The lack of sensitivity and specificity in current diagnostic techniques, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), causes diagnosis delays in RA. The miR-146a and miR-155 act in inflammatory cascades and reduce joint deterioration, and miR-223 is paradoxical, acting differently in different illness scenarios. The microenvironment of RA is shaped by the complex modulation of gene expression and cytokine dynamics by miR-126 and miR-24. miRNAs serve as a promising candidate for precision medicine in the management of RA. There are obstacles encountered in validation, delivery optimization, and off-target effect mitigation before miRNA-based biomarkers may be applied in clinical settings. Machine learning (ML) and artificial intelligence (AI) have been used to integrate miRNA expression patterns with clinical data to greatly advance the treatment of RA. Because of the disease's inherent complexity and variability, these state-of-the-art models provide accurate predictions regarding the onset, development, and response to treatment of RA. By using clinical information and miRNA expression data, ML algorithms are revolutionizing the treatment of RA by predicting the onset and course of the disease with remarkably high accuracy. The development of therapeutic modalities and miRNA profiling has great potential to transform the diagnosis, prognosis, and treatment of RA, providing fresh hope for better patient outcomes.

Evaluate the Association Between IL-37 Isoform-C and D Gene Expression with the Severity and Activity of Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a systemic, chronic autoimmune condition characterized by joint inflammation and pain, leading to the degeneration of the joints and bones, which may develop into deformities. The identification of the potential of new RA biomarkers, such as IL-37 isoforms for diagnosis and treatment applications is now under investigation. Purpose: This research aims to investigate the connection between the expression of IL37 isoform-c and IL37 isoform-d genes with RA activity and severity, their rules in diagnosis of the disease and for future RA therapeutic purposes. Methods: A case-control study was conducted on a total of 140 individuals. A total of 70 patients, who were recently diagnosed with rheumatoid arthritis by a rheumatologist, were included in the study, along with 70 control volunteers. The samples were obtained by using freshly acquired blood and serum samples via the use of RT-qPCR, ELISA, and other methods. The sample included 64 females and 6 men in both the patient and control groups. The age ranges from 20 to 70 years. Specimens were gathered between August 2023 and December 2023 from the Rheumatology department at AL-Sader Medical City in Najaf Governorate, Iraq. The blood IL-37 level was quantified using an enzyme-linked immunosorbent assay (ELISA). Additionally, immune markers including Anti-CCP, ESR, RF, and CRP were assessed. The quantification of IL-37 isoforms' gene expression was performed using qRT-PCR. The activity of rheumatoid arthritis (RA) was assessed using DAS28-ESR, DAS28-CRP, and CDAI, which also allowed for the determination of disease severity. Results: The levels of inflammatory parameters including Anti-CCP, CRP, RF, and ESR were significantly elevated in RA patients in compared to controls. IL-37 isoform-c mRNA expression, as determined by RT-qPCR, has significantly greater expression in the patients' group. It was upregulated in moderate groups of patients. Furthermore, the isoform-d gene was downregulated, in contrast to control groups for both genes, who exhibited normal expression for these genes. And there was a non-significant association between IL37 isoforms c and d expression and RA activity and severity. However, IL37-c expression increased within the moderate patient groups based on severity and activity categorization as compared to controls. Conclusion: IL37 isoform-c and isoform-d are considered as a weak biomarker for diagnosing RA, evaluating disease activity and severity for RA patients.

Elevated Cathepsin B enzyme levels: a potential risk indicator for rheumatoid arthritis: Insights from a Mendelian randomization study.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly impacts the quality of life of affected individuals. Observational data have consistently pointed towards an associative relationship between cathepsins and the development of RA. Nonetheless, the establishment of a definitive causal nexus between members of the cathepsin family and the pathogenesis of RA remains elusive. In this study, we harnessed the principles of Mendelian randomization (MR) to interrogate the putative causal association between cathepsins and RA, and a series of sensitivity analyses were used to test the reliability of the MR results. Forward MR analyses substantiated a significant genetic correlation between the genetically predicted levels of Cathepsin B and the predisposition to RA, elevated levels of Cathepsin B exhibit a significant association with an increased risk of RA (OR = 1.0727, 95% CI: 1.0171-1.1314, P = .0098). In the reverse MR and multivariable MR analyses, no significant causal relationship was identified between cathepsins and RA. The findings suggest that Cathepsin B may serve as a biomarker for RA, thereby offering significant implications for the advancement of diagnostic and therapeutic strategies in the management of RA.

Exploration of the Regulatory Network of Programmed Cell Death Genes in Rheumatoid Arthritis Based on Blood-Derived circRNA Transcriptome Information and Single-Cell Multi-omics Data.

Programmed cell death (PCD) and circular RNA (circRNA) have been found to involve in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to explore PCD mechanisms and gene regulatory networks in RA. RA related to circRNA, mRNA and single-cell data sets were obtained from the GEO database. The limma package was used to screen differentially expressed circRNA and differentially expressed genes (DEGs) of RA. The PCD gene set from literature was intersected with the DEGs of RA to obtain PCD-related DEGs of RA. The ENCORI database was used to predict and construct a competing endogenous RNAs (ceRNA) regulatory network to obtain key circRNAs and PCD-related DEGs. Hub genes were identified from the key PCD-related DEGs in the ceRNA regulatory network through LASSO regression, and a diagnostic model was constructed based on these hub genes. The expression of hub genes in various cells and stages was analyzed using single-cell datasets. Finally, the expression of key circRNAs and hub genes in peripheral blood of RA patients and healthy individuals was verified by PCR. In this study, a total of 71 differential circRNAs and 221 DEGs in RA were obtained, and 23 PCD-related DEGs were identified. Through ceRNA regulatory network, three key circRNAs (hsa_circ_0001241, hsa_circ_0089761, and hsa_circ_0001654) and four hub PCD-related DEGs. Among them, TXN and RRAGD were highly expressed, and PARP1 and TXNIP were lowly expressed in RA. Single-cell analysis revealed that these genes were significantly differentially expressed in myeloid cell subpopulation. PCR results indicated that among the 7 key factors, the expression of hsa_circ_0001241, hsa_circ_0089761, TXN, and RRAGD in RA was consistent with the results of bioinformatics analysis. Hsa_circ_0001241, hsa_circ_0089761, TXN and RRAGD may be potential biomarkers for RA, and their interactions may have significant implications for the pathology of RA.

HIPK3 hypomethylation as a potential epigenetic biomarker in rheumatic immune diseases with emphasis on rheumatoid arthritis.

This study aimed to explore the potential of HIPK3 DNA methylation as a biomarker for rheumatoid arthritis (RA) by examining its methylation levels in various rheumatic immune diseases and analyzing its correlation with clinical indicators. We recruited 368 participants, including patients with RA, ankylosing spondylitis (AS), GOUT, psoriatic arthritis (PSA), sjogren's syndrome (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), and healthy controls (HC), and MethylTargetTM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HIPK3 (cg15692052). We analyzed the HIPK3 methylation levels and correlated them with common clinical indicators. Transcriptome data from the GEO dataset (GSE93272) were also analyzed to assess HIPK3 mRNA expression levels in RA patients. Statistical analyses included Spearman correlation, One-Way ANOVA, Kruskal-Wallis tests, and ROC curve analysis. HIPK3 methylation levels were significantly lower in the RA, SLE, and DM groups compared to the HC group (P < 0.05). RA subgroups based on RF and CCP statuses also showed lower HIPK3 methylation levels compared to the HC group (P < 0.05). Analysis of the GEO dataset revealed significantly elevated HIPK3 mRNA expression in RA patients (P < 0.05). A negative correlation was found between HIPK3 methylation levels and ESR (r = -0.14, P = 7.1e-3), CRP (r = -0.25, P = 4.1e-7), RF (r = -0.18, P = 5.2e-4), and DAS28-CRP (r = -0.12, P = 0.04) in the RA group. ROC analysis indicated that HIPK3 methylation levels had high diagnostic value for RA (AUC = 0.742), SLE (AUC = 0.701), and DM (AUC = 0.948), especially in distinguishing seronegative RA (AUC = 0.612, 0.747, 0.836) and differentiating RA from AS (AUC = 0.788). The study suggests that HIPK3 hypomethylation in peripheral blood is associated with RA and correlated with inflammatory markers, such as CRP. HIPK3 methylation levels have potential as a novel biomarker for RA diagnosis and predicting inflammation trends, showing particular promise in differentiating RA from other types of arthritis. Key Points • MethylTargetTM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HIPK3 (cg15692052). • HIPK3 methylation levels have potential as a novel biomarker for RA diagnosis and predicting inflammation trends.

Synovial Fluid Markers and Extracellular Vesicles in Rheumatoid Arthritis.

In recent years, numerous potential prognostic biomarkers for rheumatoid arthritis (RA) have been investigated. Despite these advancements, clinical practice primarily relies on autoantibody tests-for rheumatoid factor (RF) and anti-citrullinated protein antibody (anti-CCP)-alongside inflammatory markers, such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Expanding the repertoire of diagnostic and therapeutic biomarkers is critical for improving clinical outcomes in RA. Emerging evidence highlights the significance of synovial fluid biomarkers, including aggrecan, matrix metalloproteinases, glucosyl-galactosyl-pyridinoline, hyaluronic acid, S100 proteins, calprotectin, and various cytokines, as well as immunological markers. Additionally, specific components of extracellular vesicles, such as non-coding RNAs, heat shock proteins, and lipids, are gaining attention. This review focuses on molecular markers found in synovial fluid and extracellular vesicles, excluding clinical and imaging biomarkers, and explores their potential applications in the diagnosis and management of RA.

Scavenger receptor-A is a sensitive disease activity biomarker in ESR and CRP normal rheumatoid arthritis.

Identification of rheumatoid arthritis (RA) patients in active disease with normal ESR and CRP is a challenge in disease activity assessment. The objective of this study was to evaluate the performance and clinical significance of Scavenger receptor-A (SRA) as a disease activity biomarker in RA, especially in ESR and CRP normal patients. One hundred and sixty-two RA (40 discovery cohort; 122 validation cohort), 20 osteoarthritis (OA), and 36 healthy controls (HCs) were recruited. Ten disease activity markers were evaluated by Bio-Plex Pro Human Cytokine Assay in the discovery cohort. SRA levels were measured by enzyme-linked immunosorbent assay (ELISA) in the validation cohort. The association between SRA and clinical phenotypes was also analyzed. ROC analysis was performed for disease activity prediction. SRA was found to be correlated with disease activity in the discovery cohort. The serum SRA level was verified by ELISA in the validation cohort, and was found to be correlated with disease activity index in RA patients, including DAS28-ESR (r = .477, p < .001), swollen joint counts, and tender joint counts; as well as inflammation markers, including ESR and CRP. In ESR and CRP normal RA, there was a strong correlation between SRA and DAS28-ESR ( = 4.564, p = .003). In addition, area under the ROC of SRA was higher than AUCESR and AUCCRP in ESR and CRP normal RA patients, suggesting that serum SRA could be more sensitive than ESR and CRP for disease activity assessment in this group of patients. In the low DAS28-ESR (≤3.2) group, the AUC of SRA for disease activity measurement was higher than that of ESR and CRP, indicating that SRA was also more sensitive than ESR and CRP in low-disease activity RA. SRA was correlated with RA disease activity and may be a sensitive serum biomarker for disease activity evaluation, especially in ESR and CRP normal patients, as well as in the low-disease activity group. SRA could be a promising marker for disease activity assessment.

Integrated multi-omics revealed that dysregulated lipid metabolism played an important role in RA patients with metabolic diseases

ObjectivesPatients with rheumatoid arthritis (RA) commonly experience a high prevalence of multiple metabolic diseases (MD), leading to higher morbidity and premature mortality. Here, we aimed to investigate the pathogenesis of MD in RA patients (RA_MD) through an integrated multi-omics approach.MethodsFecal and blood samples were collected from a total of 181 subjects in this study for multi-omics analyses, including 16S rRNA and internally transcribed spacer (ITS) gene sequencing, metabolomics, transcriptomics, proteomics and phosphoproteomics. Spearman’s correlation and protein-protein interaction networks were used to assess the multi-omics data correlations. The Least Absolute Shrinkage and Selection Operator (LASSO) machine learning algorithm were used to identify disease-specific biomarkers for RA_MD diagnosis.ResultsOur results found that RA_MD was associated with differential abundance of gut microbiota such as Turicibacter and Neocosmospora, metabolites including decreased unsaturated fatty acid, genes related to linoleic acid metabolism and arachidonic acid metabolism, as well as downregulation of proteins and phosphoproteins involved in cholesterol metabolism. Furthermore, a multi-omics classifier differentiated RA_MD from RA with high accuracy (AUC: 0.958). Compared to gouty arthritis and systemic lupus erythematosus, dysregulation of lipid metabolism showed disease-specificity in RA_MD.ConclusionsThe integration of multi-omics data demonstrates that lipid metabolic pathways play a crucial role in RA_MD, providing the basis and direction for the prevention and early diagnosis of MD, as well as new insights to complement clinical treatment options.

From a better knowledge of periodontal disease to Porphyromonas gingivalis target for rheumatoid arthritis disease activity

Periodontal disease (PD) and rheumatoid arthritis (RA) are both inflammatory diseases affecting the tooth and joint, with local inflammation associated with bone loss. Bacterial infections by oral bacteria are involved in periodontal inflammation, and the best known to be associated with PD is Porphyromonas gingivalis (Pg). A large body of recent data suggests a strong involvement of this specific bacteria, Pg, in PD outcomes, but also in RA. The aim of this review is to discuss the association between PD and Pg, RA and its mechanisms, and to determine whether targeting Pg bacteria could improve RA. Numerous epidemiological studies have already confirmed the association between PD and Pg, as well as between PD and RA, which is mainly associated with a common genetic background, the shared epitope. The involvement of Pg in pathogenesis of RA is supported by the induction of gingival citrullinated proteins and therefore of anti-citrullinated proteins antibodies, which constitute the most specific biomarker of RA. The prevalence of Pg in RA is still controversial, but studies should include patients with preclinical and early RA. Finally, recent data confirmed that targeting Pg is highly effective in improving RA.

Genomic and Serological Rheumatoid Arthritis Biomarkers, MUC5B Promoter Variant, and Interstitial Lung Abnormalities.

Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples. Determine whether genetic and serological biomarkers of RA risk in combination with the MUC5B (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans. Associations of RA-risk HLA-DRB1 alleles (*04:01, *04:08, *04:05, *04:04, *10:01) and serum RA autoantibodies with ILA in the Multi-Ethnic Study of Atherosclerosis (MESA, n=4,018) and COPDGene (n=5,963) cohorts were modeled using logistic regression and adjusted for age, sex, self-reported race and ethnicity, smoking history, body mass index, and principal components of genetic ancestry. The prevalence of an RA risk HLA-DRB1 allele was 16.5% and 21.9% in MESA and COPDGene, respectively. ILA was present in 3.9% and 11% in MESA and COPDGene, respectively. An RA risk HLA-DRB1 allele was not significantly associated with ILA in MESA and COPDGene. In MESA, higher serum levels of IgA rheumatoid factor (RF) and anti-cyclic citrullinated peptide were associated with an odds ratio (OR) for ILA of 1.20 (95% CI 1.07-1.35) and 1.19 (95% CI 1.04-1.37), respectively. Among smokers without baseline ILA, per doubling of IgM RF was associated with an OR for ILA 10 years later of 1.25 (95% CI 1.08-1.43). Associations were not significantly different by MUC5B risk allele status. RA-related HLA-DRB1 alleles were not associated with ILA, whereas higher serum levels of IgM RF among smokers without baseline ILA were associated with subsequent ILA.

Serum lncRNA ITGB2-AS1 and ICAM-1 as novel biomarkers for rheumatoid arthritis and osteoarthritis diagnosis.

The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients. Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included. Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients. Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies.

Association Between Pharmacotherapy And Circulating Hematological Profile In Rheumatoid Arthritis

Background — Hematological indices are useful predictors and prognostic biomarkers in rheumatoid arthritis (RA). Some antirheumatic drugs (ARD) have a negative effect on circulating blood cells and bone marrow and therefore may bias the interpretation of biomarker value. Objective — Our cross-sectional study aimed to demonstrate the effect of ADR use on peripheral blood indices in RA patients. Methods — This cross-sectional study was conducted on 103 adult RA patients and 21 healthy subjects at Rizgari Teaching Hospital in collaboration with the Department of Clinical Pharmacy and College of Pharmacy, Hawler Medical University, Erbil, Iraq, from January 2020 through December 2022. Patients were treated with methotrexate (MTX), hydroxychloroquine (HCQ), biologics (BL), MTX+HCQ, MTX+BL, and HCQ+BL. RA activity and complete blood count were obtained from patient records. Results — Our results implied that HCQ was associated with significantly lower hemoglobin levels, while MTX+BL was accompanied by significantly lower mean corpuscular volume. The mean platelet volume was significantly higher in all treatment groups than in healthy subjects. Conclusion — We concluded that BL use was statistically significantly associated with changes in hematological indices and ratios in patients with RA. It is important to consider the category of pharmacotherapy when interpreting circulating blood cell indices as predictors or prognostic biomarkers in RA.

Anti-inflammatory potential of polyphenols: Combining in silico prediction and in vivo data

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation and destruction, leading to significant pain and disability. Adenosine deaminase (ADA) is identified as a biomarker for RA’s inflammatory process. This study aims to investigate the potential of flavonoids and phenolic acids to inhibit ADA activity (in silico) and evaluate their anti-inflammatory effects in a RA model (in vivo). Methods: The molecular docking study was conducted using YASARA Structure 19.12.14. software following the Auto Dock 4.2 protocol. A rat model with pristane-induced arthritis was used to test the anti-inflammatory effect of selected polyphenols. The consistency of the development of the rat model was evaluated through the following indicators artistic score, paw volume, and body weight. Quercetin was administered intragastrically at doses of 150 and 400 mg/kg over 15 days. The C-reactive protein (CRP) level in serum was measured with an automatic biochemical analyzer. Statistical analyses were performed using SPSS 29.0.2.0. Results: Molecular docking simulations showed flavonoids inhibited ADA activity with inhibition constants ranging from 0.012 mM to 0.190 mM. In the in vivo RA model, quercetin significantly reduced joint inflammation and serum CRP levels at a higher dose of 400 mg/kg. Conclusion: Quercetin shows promise as an anti-inflammatory agent for RA by targeting ADA, suggesting that flavonoid-rich plant extracts could enhance RA treatment.