Detection of anti‐interferon‐α2a antibodies in chronic liver disease

Abstract

The occurrence of antibodies to interferon‐α2a (anti‐IFN‐α2a) to recombinant human IFN‐α2a was examined in chronic liver disease by a sensitive enzyme‐linked immunosorbent assay (ELISA). Naturally occurring IgG and/or IgM anti‐IFN‐α2a were found in one of 12 cases of chronic persistent hepatitis, four of 18 cases of chronic active hepatitis (CAH), two of 12 cases of liver cirrhosis, six of seven cases of primary biliary cirrhosis, nine of 11 cases of auto‐immune CAH and none of 21 normal control subjects. Fifteen patients with viral CAH were treated with recombinant IFN‐α2a. Two of them were positive prior to receipt of IFN‐α2a and their titres increased after the therapy. Two patients became positive for anti‐IFN‐α2a after the therapy. Absorption experiments revealed that anti‐IFN‐α2a cross‐reacted with native human leucocyte IFN‐α and recombinant IFN‐α2b but not with recombinant IFN‐β and ‐γ. The immunoblotting experiment confirmed the binding of antibodies to IFN. The results of anti‐IFN‐α2a obtained by antiviral, cytopathic effect assay were in good agreement with those of IgG anti‐IFN‐α2a, but not with those of IgM antibodies obtained by the ELISA. The ELISA described in the present study is a simple, sensitive and quantitative assay for anti‐IFN‐α2a. It should be useful in assessing sub‐specificities of anti‐IFN and provide valuable information to predict the effect of IFN therapy and to elucidate the immunological abnormality in liver disease.