Exosomal micrornas as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis c

BackgroundDespite recent advances of direct-antiviral agents (DAA) for Hepatitis C virus (HCV), it is still a prevalent worldwide issue and therapeutic challenge in patients with rheumatoid arthritis (RA). HCV viral replication may respond differently to biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) of different mechanism of action. Exosomal microRNA 155 (exo-miR-155) and exo-miR-122 have been implicated in modulating the host immune response and transmit anti-HCV factors to HCV-infected hepatocytes in patients with RA. However, it remains unknown how exosomal miRNAs may respond following bDMARDs and tsDMARDs treatment in HCV-infected patients with RA.ObjectivesWe aimed to study the changes of exo-miR-155 and exo-miR-122 following bDMARDs and tsDMARDs treatment in HCV-infected RA patients.MethodsWe prospectively enrolled RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors, rituximab and tofacitinib. The effect of bDMARDs and tsDMARDs on HCV viral replication were assessed using an HCV-tricistronic replicon cell system. Exo-miR-155 and 122 were detected by quantitative PCR.ResultsHCV RNA replication in hepatocytes were not affected by tofacitinib treatment. Exo-miR-155 and exo-miR-122 were significantly increased in RA patients with HCV infection compared with those without HCV infection. We observed a dramatically increase of exo-miR-122 and decreased of exo-miR-155 in patients taking rituximab compared with the TNF-α inhibitors, tofacitinib and conventional synthetic DMARD groups. Finally, a reduction of exo-miR-122 and increase of exo-miR-155 levels were detected following DAA therapy for HCV.ConclusionExo-miR-155 and exo-miR-122 were potential biomarkers for RA patients with HCV infection. Further studies are needed to confirm our findings.References[1]Liao TL, Hsieh SL, Chen YM, Chen HH, Liu HJ, Lee HC, Chen DY (2018) Rituximab may cause increased hepatitis C virus viremia in rheumatoid arthritis patients through declining exosomal microRNA-155. Arthritis Rheumatol 70: 1209-1219.Table 1.Demographics of HCV-infected RA patients with bDMARDs and tsDMARDsanti-TNF-α therapy n=3Rituximab n=3Tofacitinib n=3Age62.8 (54.0-71.4)59.9 (49.9-67.6)63.8 (55.5-70.9)Gender (female, %)2 (66.7)3 (100)2 (66.7)Disease duration (years)11.0 (8.8-14.0)11.3 (7.6-17.0)12.0 (8.2-13.8)RF (IU/ml)155.0 (102.2-324.4)363.5 (265.0-538.7)95.0 (75.4-152.6)Anti-CCP antibody (units)132.7 (83.0-210.8)160.7 (106.9-400.3)112.0 (88.0-211.8)DAS285.3 (4.9-6.5)5.3 (4.8-6.4)5.2 (4.7-6.5)Figure 1.Comparison of exo-miR-122 (left panel) and exo-miR-155 levels (right panel) in RA patients receiving different biologics. All experiments were performed in triplicate and data are presented as the mean ± SD. RTX, rituximab; TNFi: tumor necrosis factor inhibitor; Tofa, tofacitinib. **p<0.01. *** p <0.005. NS, no significantly.Disclosure of InterestsNone declared