Background Persistence of hepatitis C virus (HCV) infection and response to antiviral therapy has been shown to be associated with inappropriate levels of cytokines and microRNAs (miRNAs). miRNA levels have been reported to fluctuate during treatment. Thus they could be useful predictors for responses to treatment among HCV infected patients, thereby reducing ineffective treatments. Aim The current study aimed to investigate the relation between miRNA‐21 expression profiles, transforming growth factor β (TGF‐β) serum levels and response to treatment with the new direct antiviral drugs (sofosbuvir + daclatasvir ± ribavirin), among HCV infected Egyptian patients. Subjects and Methods This prospective study was conducted on 50 HCV infected patients (before and after treatment) and 20 healthy volunteers. miRNA expression profiles were determined by real‐time polymerase chain reaction and TGF‐β1 serum levels were measured by using enzyme‐linked immunosorbent assay. Results There was a significant increase in serum albumin, platelets count and a significant decrease in liver enzymes, serum bilirubin, and prothrombin time after treatment. Significant reduction of viral load among HCV patients after receiving the treatment was reported. Concomitantly, there was an increase in the relative quantity of miRNA‐21 (P = .001*) and serum levels of TGF‐β1 ( P = .337) among HCV patients after receiving treatment. Conclusion Nearly all responders to direct antiviral drugs showed increased levels of both miRNA‐21 and TGF‐β1. This may indicate an interplay between TGF‐β1 and miRNA‐21 during remission or progression of viral infection. Thus miRNA‐21 could be used as promising serum biomarker, for assessment of antiviral treatment efficacy and improvement of fibrosis among chronically infected HCV patients.

BackgroundIn autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), cytokines play a central role in initiating and maintaining diverse immune and inflammatory responses.In addition to IL-17A and F, Th17 cells also secrete IL-21, IL-22, and granulocyte macrophage colony-stimulating factor (GM-CSF). IL-22, member of IL-10 cytokine family, has been believed as an important player in regulating inflammatory responses associated with many inflammatory diseases. There is apparently a strong functional synergism of TNF-α and IL-22; the interaction of IL-22 & TNF-α is mediated through TNFR I and IL-22R heterodimer and intracellularly by MAP kinases. The combination of IL-22 & TNF-α strongly induced the phosphorylation and translocation of MAP kinases to the nucleus whereas the single cytokine only weakly contributed to MAP kinase activation. The discovery of the IL-22/TNF-α axis gives a first insight that could lead to new therapeutic approaches of RA.Objectivesto evaluate the role of IL-22 and TRAF1 in patients (pts) with RA & SLE, and their association to the disease activity.Methods70 RA pts, 64 SLE pts aged & 45 healthy matched controls were enrolled. DAS28 & SLEDAI were used to assess activity.ResultsIL-22 was significantly higher in RA&SLE pts than healthy controls. significant positive correlation was found between IL-22 levels and tender joints count, CRP and ESR. However, In SLE pts CRP only showed a positive correlation with IL-22 levelsComparison between TRAF1 genotyping, clinical and laboratory dataGenotypePA/AA/GG/GESR mm/hr76.40±9.6349.76±26.8151.83±37.930.006*CRP (mg/L)14.8 (14.8–71.0)15.0 (2.9–67.0)21.0 (3.0–48.0)0.152RF (IU/mL)24.0 (15.1–24.0)24.0 (6.9–359.0)10.1 (7.3–15.0)<0.001*Anti-CCP (U/mL)29.7 (29.7–30.1)33.6 (12.1–178.0)21.9 (18.0–175.4)0.690DAS285.43±0.744.48±0.914.34±0.990.001*Tender joints count4.0 (4.0–26.0)8.0 (2.0–16.0)6.0 (2.0–14.0)0.004*Swollen joints count2.0 (2.0–2.0)2.0 (0.0–12.0)2.0 (0.0–3.0)0.238Disease duration (yrs)1.0 (1.0–4.0)3.0 (0.33–20.0)2.0 (1.0–6.0)0.004*MHAQ0.60 (0.50–2.25)0.60 (0.12–0.80)0.60 (0.13–1.50)0.354*Statistical significance at p<0.05.RF +ve>20 IU/ml. Anti-CCP +ve >30 IU/ml.Analysis of TRAF1 polymorphism: in RA pts; the magnitude of association was increased in those patients who were autoantibody positive either RF+ or anti- CCP+. TRAF1 A allele was significantly associated with RF+ and anti-CCP+ RA patients when compared withcontrol. (OR =3.344 CI: 1.79–6.24, P<0.001, OR =1.881 CI: 1.03–3.41 P<0.034)respectively,in SLE pts, TRAF1 rs10818488 was not significantly different in pts and controlConclusionsTheses results indicate that IL-22 is associated with inflammatory process and it has a role in RA and SLE pathogenesis and prognosis.Although there are inconsistent findings which need to be resolved, there are a synergism between TNF-α, IL 17 & IL-22,mso,targeting IL-22 cytokine may be an effective therapeutic approach for chronic inflammation in the future.Also TRAF1 was significantly associated with RF positive, anti-CCP p...

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