Biomarker For Diagnosis Of Rheumatoid Arthritis Research Articles

Combination of scavenger receptor-A with anti-cyclic citrullinated peptide antibody for the diagnosis of rheumatoid arthritis.

The routine biomarkers for rheumatoid arthritis (RA), including anticyclic citrullinated peptide antibody (anti-CCP), rheumatoid factor (RF), immunoglobulin M (IgM), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) have limited sensitivity and specificity. Scavenger receptor-A (SR-A) is a novel RA biomarker identified by our group recently, especially for seronegative RA. Here, we performed a large-scale multicentre study to further assess the diagnostic value of SR-A in combination with other biomarkers for RA. The performance of SR-A in combination with other biomarkers for RA diagnosis was first revealed by a pilot study, and was further elucidated by a large-scale multicentre study. A total of 1129 individuals from 3 cohorts were recruited in the study, including RA patients, healthy controls, and patients with other common rheumatic diseases. Diagnostic properties were evaluated by the covariate-adjusted receiver-operating characteristic (AROC) curve, sensitivity, specificity and clinical association, respectively. Large-scale multicentre analysis showed that SR-A and anti-CCP dual combination was the optimal method for RA diagnosis, increasing the sensitivity of anti-CCP by 13% (87% vs 74%) while maintaining a specificity of 90%. In early RA patients, SR-A and anti-CCP dual combination also showed promising diagnostic value, increasing the sensitivity of anti-CCP by 7% (79% vs 72%) while maintaining a specificity of 94%. Moreover, SR-A and anti-CCP dual combination was correlated with ESR, IgM, and autoantibodies of RA patients, further revealing its clinical significance. SR-A and anti-CCP dual combination could potentially improve early diagnosis of RA, thus improving the prognosis and reducing mortality.

Comparison of Plasma Levels of MicroRNA-155-5p, MicroRNA-210-3p, and MicroRNA-16-5p in Rheumatoid Arthritis Patients with Healthy Controls in a Case-control Study.

Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation and destruction of the joints. The objective of the current study was to evaluate the expression of microRNA (miR)-155-5p, miR-210-3p, and miR-16-5p in the plasma of patients with rheumatoid arthritis in comparison with a healthy control group to attain an expression profile for earlier diagnosis and treatment. To carry out this study, 100 individuals were chosen as two equally sized groups of rheumatoid arthritis patients and healthy controls. Five milliliters of blood were drawn from each individual, and plasma RNA was extracted using Trisol solution. Complementary DNAs were synthesized using the Moloney leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Finally, real-time polymerase chain reaction (PCR) was implemented using the SYBR Green kit. The mean expression of miR-155-5p, miR-210-3p, and miR-16-5p were 2.46±2.79, 1.97±1.90, and 69.62±88.44 in the rheumatoid arthritis group, and 0.34±0.33, 9.82±9.34, and 7.94±7.09 in the healthy group, respectively. Additionally, significant differences were revealed in the relative expression of the selected microRNAs in 4 subgroups of rheumatoid arthritis patients with different disease activities based on the disease activity score 28 (DAS28). ROC curve analysis showed that miR-155-5p (area under the curve, AUC=0.90, sensitivity=80%, specificity=81%), miR-210-3p (AUC=0.75, sensitivity=66%, specificity=71%), and miR-16-5p (AUC=0.96, sensitivity=89%, specificity=82%) could be potential biomarkers for rheumatoid arthritis diagnosis. Increased expressions of miR-16-5p and miR-155-5p and decreased expression of miR-210-3p in rheumatoid arthritis patients compared with healthy individuals demonstrate the effectiveness of these microRNAs in disease incidence and progression. Thus, the expression levels of these microRNAs can be used for diagnostic and therapeutic purposes.

Circulating interleukin-39 as a potential biomarker for rheumatoid arthritis diagnosis

BackgroundImbalances in cytokine networks have been shown to be a possible cause of rheumatoid arthritis (RA). The interleukin (IL)-12 family is involved in the pathogenesis of autoimmune diseases including RA, while IL-39 is a newly discovered member of the IL-12 family, although its role in RA remains unclear. The purpose of the present study was to detect the expression of IL-39 in the sera of patients with RA and its relationship with RA activity. MethodsWe recruited 46 patients with RA and 35 healthy controls at Ningbo Sixth Hospital. Blood samples were collected for biochemical analysis, and disease activity scores of 28 joints based on C-reactive protein were monitored. Serum concentrations of IL-39 were determined using an enzyme-linked immunosorbent assay. The Pearson correlation test was used to analyze the association between serum IL-39 levels and clinical indicators. ResultsSerum levels of IL-39 were significantly higher in patients with RA compared with healthy controls (p < 0.0001). IL-39 levels positively correlated with rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and IgM; RF positively correlated with ESR. Receiver operating characteristic curve analysis showed that IL-39 has diagnostic value for RA (p < 0.0001). ConclusionsThe significant increase of IL-39 levels in serum of patients with RA and its positive correlation with clinical indicators suggest that IL-39 may serve as biomarker for the diagnosis of RA.

Oleuropein as An Effective Suppressor of Inflammation and MicroRNA-146a Expression in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common progressive autoimmune disorder that causes chronic inflammation of the joints and damage to other organs. Previous studies have reported the important role of miRNA-146a in the pathogenesis of RA. In addition, the anti-inflammatory and modulatory effects of oleuropein (OLEU) on the expression pattern of microRNAs (miRNAs) have been shown in different diseases. Therefore, this study aimed to evaluate both the sensitivity and specificity of miRNA-146a and determine the potential effects of OLEU on the expression levels of miRNA-146a and tumour necrosis factor-alpha (TNF-α) in RA patients. The participants in this experimental study were divided into 2 groups: RA (n=45) and healthy controls (n=30). The isolated peripheral blood mononuclear cells (PBMCs) were treated with different concentrations of OLEU; and the level of TNF-α expression, anti-citrullinated protein, and miRNA-146a were determined using enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. In addition, the receiver operating characteristic (ROC) curve analysis evaluated the sensitivity and specificity of miRNA-146a in RA patients. Results revealed a positive correlation between the levels of miRNA-146a expression with the serum levels of C-reactive protein (CRP) and rheumatoid factor (RF) in RA patients. In addition, OLEU treatment decreased the levels of TNF-α and miRNA-146a expression in treated PBMCs samples compared with untreated cells. The ROC curve analysis showed an 85% sensitivity and 100% specificity of miRNA-146a in RA patients. Therefore, miRNA-146a can be used as a useful biomarker for RA diagnosis, particularly for early detection. In addition, OLEU could suppress inflammation in RA patients through the regulation of miRNA-146a.

Role of the granzyme family in rheumatoid arthritis: Current Insights and future perspectives.

Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by chronic inflammation that affects synovial tissues of multiple joints. Granzymes (Gzms) are serine proteases that are released into the immune synapse between cytotoxic lymphocytes and target cells. They enter target cells with the help of perforin to induce programmed cell death in inflammatory and tumor cells. Gzms may have a connection with RA. First, increased levels of Gzms have been found in the serum (GzmB), plasma (GzmA, GzmB), synovial fluid (GzmB, GzmM), and synovial tissue (GzmK) of patients with RA. Moreover, Gzms may contribute to inflammation by degrading the extracellular matrix and promoting cytokine release. They are thought to be involved in RA pathogenesis and have the potential to be used as biomarkers for RA diagnosis, although their exact role is yet to be fully elucidated. The purpose of this review was to summarize the current knowledge regarding the possible role of the granzyme family in RA, with the aim of providing a reference for future research on the mechanisms of RA and the development of new therapies.

Validation of galectin-1 as potential diagnostic biomarker of early rheumatoid arthritis

Galectin 1 (Gal1) is a lectin with a wide cellular expression that functions as a negative regulator of the immune system in several animal models of autoimmune diseases. Identification of patients with rheumatoid arthritis (RA) has improved during the last decade, although there is still a need for biomarkers allowing an early diagnosis. In this regard, it has been recently proposed that Gal1 serum levels are increased in patients with RA compared to the general population. However, this topic is controversial in the literature. In this work, we provide additional information about the potential usefulness of Gal1 serum levels as a biomarker for RA diagnosis. We studied Gal1 serum and synovial fluid levels and clinical parameters in samples from 62 patients with early arthritis belonging to the PEARL study. In addition, 24 healthy donors were studied. We found that both patients fulfilling RA criteria and patients with undifferentiated arthritis showed higher Gal1 levels than healthy donors. Similar findings were observed in synovial fluid, which showed even higher levels than serum. However, we did not find correlation between Gal1 levels and disease activity or disability. Therefore, our results suggest that Gal1 could be a diagnostic but not a severity biomarker.

PAD enzymes in rheumatoid arthritis: pathogenic effectors and autoimmune targets

Peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) owing to their ability to generate citrullinated proteins - the hallmark autoantigens of RA. Of the five PAD enzyme isoforms, PAD2 and PAD4 are the most strongly implicated in RA at both genetic and cellular levels, and PAD inhibitors have shown therapeutic efficacy in mouse models of inflammatory arthritis. PAD2 and PAD4 are additionally targeted by autoantibodies in distinct clinical subsets of patients with RA, suggesting anti-PAD antibodies as possible biomarkers for RA diagnosis and prognosis. This Review weighs the evidence that supports a pathogenic role for PAD enzymes in RA as both promoters and targets of the autoimmune response, as well as discussing the mechanistic and therapeutic implications of these findings in the wider context of RA pathogenesis. Understanding the origin and consequences of dysregulated PAD enzyme activity and immune responses against PAD enzymes will be important to fully comprehend the pathogenic mechanisms involved in this disease and for the development of novel strategies to treat and prevent RA.

MicroRNAs in rheumatoid arthritis: From pathogenesis to clinical impact

Over the last decade, many epigenetic mechanisms that contribute in the pathogenesis of autoimmune disorders have been revealed. MicroRNAs (miRNAs) are small, non-coding, RNA molecules that bind to messenger RNAs and disrupt the transcription of target genes. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which a plethora of epigenetic changes take place. Current research on RA epigenetics has focused mainly on miRNAs. Genetic variance of some miRNA genes, especially miR-499, might predispose an individual to RA development. Additionally, altered expression of many miRNAs has been discovered in several cells, tissues and body fluids in patients with RA. MiRNAs expression also differs depending on disease's stage and activity. Serum miR-22 and miR-103a might predict RA development in susceptible individuals (pre-RA), while serum miR-16, miR-24, miR-125a and miR-223 levels are altered in early RA (disease duration <12 months) patients compared to established RA or healthy individuals. Moreover, serum miR-223 levels have been associated with RA activity and disease relapse. What is more, serum levels of several miRNAs, including miR-125b and miR-223, could be used to predict response to RA treatment. Finally, miRNA analogs or antagonists have been used as therapeutic regimens in experimental arthritis models and have demonstrated promising results. In conclusion, the research on the miRNA alterations in RA sheds light to several aspects of RA pathogenesis, introduces new biomarkers for RA diagnosis and treatment response prediction and offers the opportunity to discover new, targeted drugs for patients with RA.

Expression Profile of Long Noncoding RNAs, lnc-Cox2, and HOTAIR in Rheumatoid Arthritis Patients.

Despite the increased proof that long noncoding RNAs (lncRNAs) can control gene expression and broadly affect the normal physiological and disease conditions, the part of lncRNAs in rheumatoid arthritis (RA) is not well known. This study aimed to assess the serum expression levels of lnc-Cox2 and HOTAIR in RA and to investigate their role as novel noninvasive biomarkers in diagnosis of RA. Also, their relations with the levels of interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and with other clinicolaboratory data in RA patients were analyzed. LncRNAs-Cox2 and HOTAIR expression levels were detected in serum by real-time quantitative polymerase chain reaction. Both IL-6 and MMP-9 levels in serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of lncRNA-Cox2 and HOTAIR was significantly upregulated in RA patients compared with healthy controls. Serum levels of both IL-6 and MMP-9 were significantly higher in RA patients than in healthy subjects (P < 0.001 each). Receiver operating characteristic (ROC) curve demonstrated that lncRNA-Cox2 and HOTAIR could discriminate RA patients from healthy controls. HOTAIR (not lnc-Cox2) was observed to be an independent predictor for RA using multiple logistic regression analysis. We concluded that lnc-Cox2 and HOTAIR serum expression levels can be used as novel noninvasive biomarkers for the diagnosis of RA.

Serum miR-210 and miR-155 expression levels as novel biomarkers for rheumatoid arthritis diagnosis

Background: MicroRNAs play a crucial role in the regulation of immune response. We hypothesised roles for serum miR-210 and miR-155 in the diagnosis of rheumatoid arthritis (RA) and relationships with the clinical and laboratory variables including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β).Methods: MiR-210 and miR-155 levels were identified by real-time polymerase chain reaction (PCR). TNF-α and IL-1β were measured by enzyme-linked immunosorbent assay and routine markers by standard techniques in 100 patients with RA and 100 individuals as healthy controls. Disease activity in the patients was assessed by DA-S28.Results: MiR-210 was lower in RA compared to controls [median/IQR 0.96 (0.8–1.24) vs. 4 (1.28–3.93), p < 0.001]. miR-210 correlated inversely with clinical and laboratory variables including TNF-α and IL-1β (both r = −0.96, p < 0.001). MiR-155 expression was increased in RA compared to controls [median/IQR 6 (3.5–8.1) vs. 1.0 (0.95–1.6), p < 0.001] and correlated with TNF-α and IL-1β (both r = 0.94, p < 0.001). In multivariate analysis, miR-210 and miR-155 were both independent diagnostic markers for RA, and both were associated with RA disease activity.Conclusion: Serum miR-210 and miR-155 levels are independent diagnostic markers for RA, out-performing several routine indices and reflect disease activity. Thus, miR-210 and miR-155 might serve as non-invasive biomarkers for the diagnosis of RA.