[Research Articles] Clearance of pegylated interferon by Kupffer cells limits NK cell activation and therapy response of patients with HBV infection

Pegylated interferon-α (PEG–IFN-α), where IFN-α is attached to polyethylene glycol (PEG), is an approved treatment for chronic hepatitis B virus (HBV) infection, a disease that causes liver-related morbidity and mortality in 257 million people worldwide. It is unknown why only a minority of patients respond to PEG–IFN-α. Using sequential blood samples and liver biopsies of patients with chronic HBV infection before, during, and after PEG–IFN-α treatment, we find that patients with early natural killer (NK) cell activation after PEG–IFN-α injection experienced greater liver inflammation, lysis of HBV-infected hepatocytes, and hepatitis B surface antigen (HBsAg) decline than those without. NK cell activation was associated with induction of interferon-stimulated genes and determined by PEG–IFN-α pharmacokinetics. Patients with delayed increases in PEG–IFN-α concentrations had greater amounts of PEG-specific immunoglobulin M (IgM) immune complexes in the blood and more PEG and IgM detected in the liver than patients with rapid increase in PEG–IFN-α concentration. This was associated with reduced NK cell activation. These results indicate that the immunomodulatory functions of PEG–IFN-α, particularly activation of NK cells, play a pivotal role in the response to treatment and further demonstrate that these functions are affected by PEG–IFN-α pharmacokinetics. Ac...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research