Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C

Abstract Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respon...

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Main Authors: Tsai-Ling Liao, I-Chieh Chen, Hong-Wei Chen, Kuo-Tung Tang, Wen-Nan Huang, Yi-Hsing Chen, Yi-Ming Chen
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-50963-y
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author Tsai-Ling Liao
I-Chieh Chen
Hong-Wei Chen
Kuo-Tung Tang
Wen-Nan Huang
Yi-Hsing Chen
Yi-Ming Chen
author_facet Tsai-Ling Liao
I-Chieh Chen
Hong-Wei Chen
Kuo-Tung Tang
Wen-Nan Huang
Yi-Hsing Chen
Yi-Ming Chen
author_sort Tsai-Ling Liao
collection DOAJ
description Abstract Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.
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spelling doaj.art-f291585d2e8c44428b52bdee3c57963c2024-01-14T12:23:16ZengNature PortfolioScientific Reports2045-23222024-01-0114111010.1038/s41598-023-50963-yExosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis CTsai-Ling Liao0I-Chieh Chen1Hong-Wei Chen2Kuo-Tung Tang3Wen-Nan Huang4Yi-Hsing Chen5Yi-Ming Chen6Department of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalRong-Hsing Research Center for Translational Medicine, National Chung-Hsing UniversityDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General HospitalDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalAbstract Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.https://doi.org/10.1038/s41598-023-50963-y
spellingShingle Tsai-Ling Liao
I-Chieh Chen
Hong-Wei Chen
Kuo-Tung Tang
Wen-Nan Huang
Yi-Hsing Chen
Yi-Ming Chen
Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C
Scientific Reports
title Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C
title_full Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C
title_fullStr Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C
title_full_unstemmed Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C
title_short Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C
title_sort exosomal micrornas as biomarkers for viral replication in tofacitinib treated rheumatoid arthritis patients with hepatitis c
url https://doi.org/10.1038/s41598-023-50963-y
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