Biomarker Of Disease Activity In Rheumatoid Arthritis Research Articles

Circulating microRNA-23b as a new biomarker for rheumatoid arthritis

MicroRNA-23b (miR-23b) is associated with inflammation and autoimmune diseases. This study evaluated miR-23b expression and assessed its potential as a biomarker of disease activity for rheumatoid arthritis (RA). Differential expression of microRNAs was determined by miRNA microarray analysis in fibroblast-like synoviocytes (FLSs) from four trauma patients as healthy controls (HCs) and eight RA patients. The microarray results showed elevated expression of miR-23b in FLSs from RA patients and this finding was corroborated by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization using synovial tissues (STs). Furthermore, we found miR-23b levels in plasma of RA patients were significantly higher than in HCs, and plasma miR-23b levels positively correlated with the erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP), C-reactive protein (CRP), DAS28, and platelet (PLT) count (P < 0.05). MiR-23b levels in plasma inversely correlated with the levels of hemoglobin (Hb), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but not with rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA) (P > 0.05). Moreover, patients with anorexia showed higher levels of miR-23b in plasma than those without anorexia. Similar results were observed with fatigue. Appropriate treatment for RA not only ameliorated the disease condition but also reversed the elevated plasma miR-23b level remarkably. These results suggest that circulating miR-23b may be a promising biomarker for RA disease activity.

Circulating IL-27 Is Elevated in Rheumatoid Arthritis Patients.

Cytokines are key immunoregulatory molecules that regulate T lymphocyte-mediated immune responses and inflammatory reactions. We determined whether there is aberrant expression of interleukin-27 (IL-27) in rheumatoid arthritis (RA) patients and investigated the clinical significance of these changes. IL-27 is a key cellular factor that regulates the differentiation of CD4+ T cells, which can secrete interleukin-10 (IL-10) and interleukin-17 (IL-17) in vivo. Concentrations of serum IL-27 in 67 RA patients, and 36 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay (ELISA). Results showed that concentrations of serum IL-27 in all RA patients were significantly higher than in healthy control subjects, and there was a significant and positive correlation between serum IL-27 levels and disease activity in all RA patients. Levels of serum IL-27 in RA patients were significantly correlated with disease activity score in 28 joints (DAS28). Moreover, immunosuppressive treatment with leflunomide downregulated the levels of IL-27 in active RA patients. Therefore, the elevated production of circulating T cell inflammatory factors contributes to the pathogenesis of RA, and serum IL-27 could potentially serve as a new biomarker of RA disease activity.

Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti-interleukin-6 biologic therapy in rheumatoid arthritis.

To investigate whether leucine-rich α2 -glycoprotein (LRG) could be a biomarker for disease activity during interleukin-6 (IL-6) blockade treatment of rheumatoid arthritis (RA). In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme-linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C-reactive protein (CRP) and LRG were evaluated after treatment with anti-IL-6 receptor antibody. Among tocilizumab-treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL-6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL-6 blockade-treated monkeys with low levels of CRP. Under conditions of IL-6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL-6 blockade treatment.

AB0148 Leucine-Rich Alpha-2 Glycoprotein is A Potential Disease Activity Marker under IL-6 Suppression in Autoimmune Arthritis

BackgroundC-reactive protein (CRP) is frequently used to evaluate inflammation in patients with rheumatoid arthritis (RA). However, CRP is normalized when IL-6 function is potently suppressed by anti-cytokine biologics such as...

Frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells correlate with disease activity in rheumatoid arthritis

Objective. Rheumatoid arthritis (RA) is a common autoimmune disease that is primarily driven by effector T cells, particularly Th17 cells, which are mainly contained within CD4+CD161+ T cells. Thus, we aimed to explore whether the frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were correlated with RA disease activity.Methods. The surface phenotype and cytokine production of blood were analyzed by flow cytometry in 52 RA patients and 17 healthy controls. The disease activity was evaluated by the 28-joint disease activity score.Results. The frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were increased in RA patients, and they were elevated in patients with active disease status compared to patients with low disease status. Furthermore, their frequencies were positively correlated with disease activity parameters. Receiver operating characteristic curve analysis revealed that IL-17-producing CD4+CD161+ T cell levels were able to distinguish disease activity with 60.7 % sensitivity and 87.5 % specificity, while CD4+CD161+ T cell levels showed 92.9 % sensitivity and 66.7 % specificity.Conclusion. These results support the hypothesis that Th17 cells are involved in the pathogenesis of RA and suggest that circulating CD4+CD161+ T cells are a potential biomarker of RA disease activity.

A functional variant in FCRL3 is associated with higher Fc receptor–like 3 expression on T cell subsets and rheumatoid arthritis disease activity

CD4+FoxP3+ Treg cells suppress effector T cells and prevent autoimmune disease. Treg cell function is deficient in active rheumatoid arthritis (RA), a loss which may play a role in the pathogenesis of this disease. We previously showed that a single-nucleotide polymorphism in the FCRL3 gene led to higher expression of Fc receptor-like 3 (FcRL3) on Treg cells and that FcRL3+ Treg cells are functionally deficient in comparison to FcRL3- Treg cells. This study was undertaken to investigate the potential role of FcRL3 in RA. A cross-sectional study was performed to evaluate the FCRL3 -169 genotype and FcRL3 expression on T cell subsets, including Treg cells, in peripheral blood samples from 51 patients with RA enrolled in the University of California, San Francisco (UCSF) RA Cohort. Clinical data were obtained from the UCSF RA Cohort database. Patients with the FCRL3 -169C allele (genotype C/C or C/T) expressed higher levels of FcRL3 on Treg cells, and on CD8+ and γ/δ T cells, in comparison to RA patients with the T/T genotype. Higher FcRL3 expression on these T cell subpopulations correlated with RA disease activity in patients harboring the FCRL3 -169C allele. Furthermore, FcRL3 expression on Treg cells was higher in patients with erosive RA, and the FCRL3 -169C allele was overrepresented in patients with erosive RA. Our findings indicate that FcRL3 expression, which is strongly associated with the presence of the FCRL3 -169C allele, may serve as a biomarker for RA disease activity.

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<h3>Background</h3> Dissociation between the responses of a number of acute-phase proteins (APP) is well known. C reactive protein (CRP) levels have been used extensively to model disease activity in rheumatoid arthritis (RA). However, biologic therapy reduce CRP levels, even without associated reductions in RA disease activity. Serum amyloid A (SAA) also models RA disease activity and has been suggested as a better biomarker for RA disease activity. <h3>Objectives</h3> To determine if SAA levels had better correlation with conventional clinical and serological assessments in RA than CRP and ESR. <h3>Methods</h3> A cross-sectional study was performed. Samples were analyzed from RA patients under biologic therapy of a reference hospital in northern Portugal. We compared the correlation between SAA, CRP and ESR levels with swollen and tender joints counts (SJC and TJC), DAS28-4v, SDAI, CDAI, HAQ and visual analogue scale for pain (VAS-P). Correlation was calculated using the Spearman rank correlation (r). P-values &lt;0.05 were regarded as significant. <h3>Results</h3> 173 patients were evaluated, 86.7% (n=150) were women. The mean (SD) age was 56 years (10.75). Mean disease duration was 16.31 years (8.87). Most of patients had positive serology (rheumatoid factor and/or anti-CCP antibody) (n=146, 84.4%). Ninety eight patients (56.6%) were under TNF antagonists, 23.7% (n=41) were under rituximab and the remaining under tocilizumab (TCZ). SAA levels were moderately correlated with CRP levels (r=0.49, p&lt;0.001) but there was no statistically significant correlation with ESR (r=0.03, p=0.75). Correlation analysis of SAA and CRP levels with several conventional assessments showed (SAA and CRP, respectively): SJC - 0.17 vs 0.08, TJC - 0.18 vs 0.09, DAS28-4v - 0.32 vs 0.41, SDAI - 0.23 vs 0.18, CDAI - 0.18 vs 0.11, ESR – 0.32 vs 0.55; all p values &lt;0.05 except SJC, TJC and SDAI for CRP values. There was no statistically significant correlation of these acute-phase protein with HAQ and VAS-P. ESR levels showed very weak correlation with all parameters (p&gt;0.05), except with DAS28-4v (r=0.58, p&lt;0.001). We also noted that SAA levels were raised (&gt;6.4mg/L) in 37.6% (n=65) of patients in which the CRP concentration was normal (&lt;0.3mg/dL). However, only 6% (n=11) with normal SAA levels had raised concentrations of CRP. When evaluated SAA and CRP levels in patients with active disease (DAS28-4v ³2.6, SDAI&gt;3.3 and CDAI&gt;2.8) we found more patients with normal CRP values than SAA (62 vs 26, 82 vs 32, 84 vs 33, respectively). Interestingly, when comparing the effects of biological therapy on APP we noted that in TCZ group the CRP, ESR and SAA levels were lower than in group under TNF antagonists and rituximab (p&lt;0.001 for all, Mann-Whitney test). <h3>Conclusions</h3> The lack of a strong correlation between SAA and CRP or ESR levels coupled with their better correlation with markers of RA activity suggests that changes in their levels may provide a more sensitive indicator of disease activity, especially during treatment with biologic therapy. <h3>Disclosure of Interest</h3> None declared