European Journal of Biomedical and Pharmaceutical Sciences

ROLE OF MXA AND NEUTRALIZING ANTIBODIES IN EARLY RESPONSE TO INTERFERON TREATMENT IN HEPATITIS C EGYPTIAN PATIENTS

Mohammed Ali Saber*, Safia Samir El-Naggar, Moatz Hassen Hassanein and Ahmed Barakat Barakat

ABSTRACT

Pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) treatment does not succeed to attain a sustained virological response (SVR) in about 20-50% of patients with chronic hepatitis C virus (HCV) infection. It has been found that Myxovirus resistance protein A (MxA) gene expression is a reliable and sensitive marker for the presence of exogenous type I interferons (IFNs) during IFN treatment. In addition, considering the involvement of anti-IFN-α binding antibodies (anti-IFN-α2a IgG Abs) and anti-IFN-α neutralizing antibodies (NAbs) on the nonresponse to treatment with PEG-IFN-α2a/RBV, Fifty-two PEG-IFN-α2a/RBV treated patients and sixteen healthy controls (without Hepatitis C) were enrolled in this study. We examined the correlation between MxA gene expression, anti-IFN-α2a IgG Abs and NAbs and the early response to treatment. Quantification of MxA mRNA performed by real-time PCR showed a statistical significant elevation in the mean value of MxA mRNA in early virological responders (EVR) (4.10±1.54) when compared with both controls (3.19±0.89, P ≤ 0.026) and non-early virological responders (non-EVRs) (2.56±1.09, P ≤ 0.001). Anti-IFN-α2a IgG Abs were assessed using indirect ELISA. The percentage of positivity of anti-IFN-α2a IgG antibodies in EVRs was 2/26 (7.7%) and in non-EVRs 4/26 (15.4%). There was no statistical significant difference between the mean values of anti-IFN-α2a IgG antibodies in EVRs (0.46±0.06) and non-EVRs (0.52±0.11), (p ≤ 0.321).). NAbs were distinguished by means of a neutralizing antibody assay that evaluated the neutralizing effects of serum samples against PEG-IFN-α2a. Serum samples were assessed for the presence of NAbs using rabbit polyclonal antihuman IFN-α2a as a positive control. In the 26 EVRs, no NAbs were detected. Of the 26 non-EVRs, two (7.7%) were positive for NAbs (p ≤ 0.149)). This study ensured the importance of the detection of MxA expression as a factor for early assessing the probability of HCV genotype 4 patients to respond to treatment with PEG-IFN-α2a/RBV. Also, it showed that antibody production against IFN-α2a in patients getting treatment for chronic HCV infection is not a significant issue in early prediction of response and is not hindering the response to treatment.

Keywords: anti-interferon-? NAb, chronic hepatitis C, non-response, pegylated interferon-?2a, MxA, indirect ELISA, qRT-PCR and neutralizing antibody assay.