A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis
BackgroundThe etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis o...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:948a49520cfe4350b4a002ad6f715e262021-11-15T06:46:32ZA Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis1664-322410.3389/fimmu.2021.790880https://doaj.org/article/948a49520cfe4350b4a002ad6f715e262021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.790880/fullhttps://doaj.org/toc/1664-3224BackgroundThe etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis of autoimmune diseases. We sought to discover a serum biomarker panel for the early detection of RA based on exomiRNAs and inflammatory markers.MethodsA 179 miRNAs-microarray panel was analyzed in a pilot study (4 early RA and 4 controls). Validation of deregulated exomiRNAs was performed in a larger cohort (24 patients with early RA and 24 controls). miRNet software was used to predict exomiRNA gene-targets interactions. Potentially altered pathways were analyzed by Reactome pathway database search. STRING database was used to predict protein-protein interaction networks. Enzyme-linked immunosorbent assay was used to measure serum levels of sTWEAK and sCD163. Signature biomarker candidates were statistical analyzed.ResultsWe detected 11 differentially expressed exomiRNAs in early RA pilot study. Validation analysis revealed that 6/11 exomiRNAs showed strong agreement with the pilot microarray data (exomiR-144-3p, -25-3p, -15a-5p, -451a, -107 and -185-5p). sTWEAK and sCD163 biomarkers were significantly elevated in the serum of patients with early RA. Receiver operating characteristic (ROC) analysis showed that the best panel to diagnose early RA contained exomiR-451a, exomiR-25-3p and sTWEAK, and could correctly classify 95.6% of patients, with an area under the ROC curve of 0.983 and with 100% specificity and 85.7% sensitivity. The YWHAB gene was identified as a common target of the putative miRNA-regulated pathways.ConclusionA novel serum biomarker panel composed of exomiR-451a, exomiR-25-3p and serum levels of sTWEAK may have use in the early clinical diagnosis of RA. A new predicted exomiRNA-target gene YHWAB has been identified and may have a relevant role in the development of RA.Samantha Rodríguez-MuguruzaSamantha Rodríguez-MuguruzaAntonio Altuna-CoyAntonio Altuna-CoySonia Castro-OreiroMaria José Poveda-ElicesRamon Fontova-GarroféRamon Fontova-GarroféMatilde R. ChacónMatilde R. ChacónFrontiers Media S.A.articleearly rheumatoid arthritissTWEAKsCD163exomiRNAsexosomesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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early rheumatoid arthritis sTWEAK sCD163 exomiRNAs exosomes Immunologic diseases. Allergy RC581-607 |
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early rheumatoid arthritis sTWEAK sCD163 exomiRNAs exosomes Immunologic diseases. Allergy RC581-607 Samantha Rodríguez-Muguruza Samantha Rodríguez-Muguruza Antonio Altuna-Coy Antonio Altuna-Coy Sonia Castro-Oreiro Maria José Poveda-Elices Ramon Fontova-Garrofé Ramon Fontova-Garrofé Matilde R. Chacón Matilde R. Chacón A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis |
| description |
BackgroundThe etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis of autoimmune diseases. We sought to discover a serum biomarker panel for the early detection of RA based on exomiRNAs and inflammatory markers.MethodsA 179 miRNAs-microarray panel was analyzed in a pilot study (4 early RA and 4 controls). Validation of deregulated exomiRNAs was performed in a larger cohort (24 patients with early RA and 24 controls). miRNet software was used to predict exomiRNA gene-targets interactions. Potentially altered pathways were analyzed by Reactome pathway database search. STRING database was used to predict protein-protein interaction networks. Enzyme-linked immunosorbent assay was used to measure serum levels of sTWEAK and sCD163. Signature biomarker candidates were statistical analyzed.ResultsWe detected 11 differentially expressed exomiRNAs in early RA pilot study. Validation analysis revealed that 6/11 exomiRNAs showed strong agreement with the pilot microarray data (exomiR-144-3p, -25-3p, -15a-5p, -451a, -107 and -185-5p). sTWEAK and sCD163 biomarkers were significantly elevated in the serum of patients with early RA. Receiver operating characteristic (ROC) analysis showed that the best panel to diagnose early RA contained exomiR-451a, exomiR-25-3p and sTWEAK, and could correctly classify 95.6% of patients, with an area under the ROC curve of 0.983 and with 100% specificity and 85.7% sensitivity. The YWHAB gene was identified as a common target of the putative miRNA-regulated pathways.ConclusionA novel serum biomarker panel composed of exomiR-451a, exomiR-25-3p and serum levels of sTWEAK may have use in the early clinical diagnosis of RA. A new predicted exomiRNA-target gene YHWAB has been identified and may have a relevant role in the development of RA. |
| format |
article |
| author |
Samantha Rodríguez-Muguruza Samantha Rodríguez-Muguruza Antonio Altuna-Coy Antonio Altuna-Coy Sonia Castro-Oreiro Maria José Poveda-Elices Ramon Fontova-Garrofé Ramon Fontova-Garrofé Matilde R. Chacón Matilde R. Chacón |
| author_facet |
Samantha Rodríguez-Muguruza Samantha Rodríguez-Muguruza Antonio Altuna-Coy Antonio Altuna-Coy Sonia Castro-Oreiro Maria José Poveda-Elices Ramon Fontova-Garrofé Ramon Fontova-Garrofé Matilde R. Chacón Matilde R. Chacón |
| author_sort |
Samantha Rodríguez-Muguruza |
| title |
A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis |
| title_short |
A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis |
| title_full |
A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis |
| title_fullStr |
A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis |
| title_full_unstemmed |
A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis |
| title_sort |
serum biomarker panel of exomir-451a, exomir-25-3p and soluble tweak for early diagnosis of rheumatoid arthritis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/948a49520cfe4350b4a002ad6f715e26 |
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