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Circulating lnc-ITSN1-2 expression presents a high value in diagnosis of rheumatoid arthritis and correlates with disease activity.

ABSTRACT: This study was aimed to investigate the correlation of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 expressions in plasma by qPCR with rheumatoid arthritis (RA) risk and disease activity. 30 RA patients and 30 health controls (HC) were enrolled in this study. Plasma sample were collected from RA patients before any treatment carried out and HCs. Top 3 RA related long non-coding RNAs (lncRNAs) (lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1) were selected by a computational framework prediction. The expression of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 were determined by qPCR method. Age (P=0.350) and gender (P=0.542) were similar between RA patients and HCs. lnc-ITSN1-2 level was extremely increased in RA patients compared with HCs (P<0.001), while both lnc-APOC3-2 and lnc-AL355149.1 expressions were numerically higher in RA patients but with no statistical significance (P=0.152 and P=0.139 respectively). Receiver Operating Characteristic (ROC) curves were performed and we found lnc-ITSN1-2 disclosed a great diagnostic value for RA with area under curve (AUC) 0.898, 95% CI 0.813-0.983, and sensitivity was 90.0% and specificity was 80.0% respectively at the best cut-off point. In addition, plasma lnc-ITSN1-2 level was illuminated to be positively associated with erythrocyte sedimentation rate (ESR) (P=0.049), C-reactive protein (CRP) (P<0.001) and disease activity score in 28 joints (DAS28) (P=0.007). Circulating lnc-ITSN1-2 expression was observed to be a novel and convincing biomarker for RA diagnosis as well as disease management.

SUBMITTER: Gong X

PROVIDER: S-EPMC6965784 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Circulating lnc-ITSN1-2 expression presents a high value in diagnosis of rheumatoid arthritis and correlates with disease activity.

Gong Xuming X Fan Xiaolei X Zhang Zhanming Z Cai Qiang Q Guo Mengru M Gao Chenxin C Xiao Lianbo L Yue Tao T

International journal of clinical and experimental pathology 20171001 10

This study was aimed to investigate the correlation of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 expressions in plasma by qPCR with rheumatoid arthritis (RA) risk and disease activity. 30 RA patients and 30 health controls (HC) were enrolled in this study. Plasma sample were collected from RA patients before any treatment carried out and HCs. Top 3 RA related long non-coding RNAs (lncRNAs) (lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1) were selected by a computational framework prediction. The ...[more]

PMID: 31966382

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Project description:ObjectivesTo assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients.MethodsPeripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis.ResultsThe methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10-3 ) and in the HC group (p = 5.5 × 10- 4 ). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti-cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970-0.995). The methylation level of cg04537602 in RA was positively correlated with C-reactive protein (CRP) (r = .16, p = .01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r = .31, p = 4.7 × 10- 4 ), tender joint count (r = .21, p = .02), visual analog scales score (r = .21, p = .02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28-CRP (r = .27, p = 2.1 × 10- 3 ), and DAS28-ESR (r = .22, p = .01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single-loci-based CpG methylation measurement.ConclusionThe methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients.

Project description:BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease of which the pathogenetic mechanisms are not fully understood. Semaphorin3A (Sema3A) has an immune regulatory role. Neuropilin1 (NRP1), the primary receptor for Sema3A, is also a receptor for vascular endothelial growth factor 165 (VEGF 165). It has been shown that Sema3A competitively antagonizes VEGF 165 signaling. This study investigated whether Sema3A is expressed in synovial tissues, and is associated with disease activity and the histological features of synovial tissues from RA patients. METHODS: Human synovial tissues samples were obtained from RA and osteoarthritis (OA) patients. Disease activity of RA patients was calculated using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The histological features of RA synovial tissues were evaluated using Rooney's inflammation scoring system. The localization of Sema3A, VEGF 165 and NRP1 positive cells was immunohistochemically determined in synovial tissues. Expression levels of Sema3A, VEGF-A and NRP1 mRNA were determined using quantitative real-time polymerase chain reaction (qPCR). RESULTS: In OA specimens, Sema3A, VEGF 165 and NRP1 proteins were expressed in the synovial lining and inflammatory cells beneath the lining. Immunohistochemistry revealed the protein expression of Sema3A in synovial lining cells was decreased in RA tissues compared with OA samples. qPCR analysis demonstrated a significant reduction of Sema3A mRNA levels in RA synovial tissue samples than in OA and a significant correlation of the ratio of Sema3A/VEGF-A mRNA expression levels with DAS28-CRP (R = -0.449, p = 0.013). Sema3A mRNA levels also correlated with Rooney's inflammation score, especially in perivascular infiltrates of lymphocytes (R = -0.506, p = 0.004), focal aggregates of lymphocytes (R = -0.501, p = 0.005) and diffuse infiltrates of lymphocytes (R = -0.536, p = 0.002). CONCLUSIONS: Reduction of Sema3A expression in RA synovial tissues may contribute to pathogenesis of RA.

Project description:IntroductionSurfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA.MethodsOne-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed.ResultsSerum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings.ConclusionsThis study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation.Trial registration(j.nr NCT00209859).

Project description:OBJECTIVE:To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). METHODS:This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. RESULTS:441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (? = -0.11, p<0.01), Simplified Disease Activity Index (SDAI) (? = -0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (? = -0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (? = -0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: "seafoods", "vegetables/fruits", "meats/fried foods", "snacks", and "processed foods". The multivariate analysis adjusted for clinically significant confounders showed that "seafoods" had statistically significant negative correlations with DAS28-ESR (? = -0.15, p<0.01), SDAI (? = -0.18, p<0.001), MMP-3 (? = -0.15, p<0.01), and HAQ (? = -0.24, p<0.0001). "Vegetables/fruits" had statistically significant negative correlations with SDAI (? = -0.11 p<0.05), MMP-3 (? = -0.12, p<0.01), and HAQ (? = -0.11, p<0.05). CONCLUSIONS:These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.

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Circulating lnc-ITSN1-2 expression presents a high value in diagnosis of rheumatoid arthritis and correlates with disease activity.

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Circulating lnc-ITSN1-2 expression presents a high value in diagnosis of rheumatoid arthritis and correlates with disease activity.

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