Novel biomarkers of a peripheral blood interferon signature associated with drug-naïve early arthritis patients distinguish persistent from self-limiting disease course
| العنوان: | Novel biomarkers of a peripheral blood interferon signature associated with drug-naïve early arthritis patients distinguish persistent from self-limiting disease course |
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| المؤلفون: | Adam P. Cribbs, Yongjing Guo, Sundeept Bhalara, Bernard Gregory, Lih-Ling Lin, Marc Feldmann, Attila A. Seyhan, Yizheng Li, Ying Zhang, Christine Loreth, Lynn M. Williams, Peter C. Taylor, Fionula M. Brennan |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) Scientific Reports |
| بيانات النشر: | Springer Nature, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Candidate gene, Inflammatory arthritis, Acute inflammatory arthritis, Arthritis, lcsh:Medicine, Real-Time Polymerase Chain Reaction, Gastroenterology, Article, Arthritis, Rheumatoid, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Immunogenetics, medicine, Humans, lcsh:Science, Aged, Aged, 80 and over, 030203 arthritis & rheumatology, Multidisciplinary, business.industry, lcsh:R, Area under the curve, Early Inflammatory Arthritis, Middle Aged, Gene signature, Microarray Analysis, medicine.disease, Arthralgia, Drug-naïve, Gene Ontology, 030104 developmental biology, ROC Curve, Area Under Curve, Case-Control Studies, Rheumatoid arthritis, Interferon Type I, Female, lcsh:Q, Transcriptome, business, Biomarkers, medicine.drug |
| الوصف: | We profiled gene expression signatures to distinguish rheumatoid arthritis (RA) from non-inflammatory arthralgia (NIA), self-limiting arthritis (SLA), and undifferentiated arthritis (UA) as compared to healthy controls as novel potential biomarkers for therapeutic responsiveness. Global gene expression profiles of PBMCs from 43 drug-naïve patients presenting with joint symptoms were evaluated and differentially expressed genes identified by comparative analysis with 24 healthy volunteers. Patients were assessed at presentation with follow up at 6 and 12 months. Gene ontology and network pathway analysis were performed using DAVID Bioinformatics Resources v6.7. Gene expression profiles were also determined after disease-modifying anti-rheumatic drug (DMARD) treatment in the inflammatory arthritis groups (i.e. RA and UA) and confirmed by qRT-PCR. Receiver operating characteristic (ROC) curves analysis and Area Under the Curve (AUC) estimation were performed to assess the diagnostic value of candidate gene expression signatures. A type I interferon (IFN) gene signature distinguished DMARD-naïve patients who will subsequently develop persistent inflammatory arthritis (i.e. RA and UA) from those with NIA. In patients with RA, the IFN signature is characterised by up-regulation of SIGLEC1 (p = 0.00597) and MS4A4A (p = 0.00000904). We also identified, EPHB2 (p = 0.000542) and PDZK1IP1 (p = 0.0206) with RA-specific gene expression profiles and elevated expression of the ST6GALNAC1 (p = 0.0023) gene in UA. ROC and AUC risk score analysis suggested that MSA4A (AUC: 0.894, 0.644, 0.720), PDZK1IP1 (AUC: 0.785, 0.806, 0.977), and EPHB2 (AUC: 0.794, 0.723, 0.620) at 0, 6, and 12 months follow-up can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. In patients with early inflammatory arthritis, ST6GALNAC1 is a potential biomarker for UA as compared with healthy controls whereas EPHB2, MS4A4A, and particularly PDZK1IP1 may discriminate RA patients. SIGLEC1 may also be a useful marker of disease activity in UA. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24bccac40f02ddb5c763c49b32feaddb https://doi.org/10.1038/s41598-020-63757-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....24bccac40f02ddb5c763c49b32feaddb |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |