Immunochemical characterization of human antibodies to lymphoblastoid interferon

Antibodies produced in recurrent respiratory papillomatosis (RRP) patients treated with lymphoblastoid interferon (lyIFN) may neutralize antiviral activity or may only bind to lyIFN. These antibodies were characterized for immunoglobulin class, IgG subclass, and light chain type by an indirect immunoassay. Serum dilutions were incubated on lyIFN-coated plates and the presence of antibody detected using peroxidase-conjugated goat antibodies to each human immunoglobulin class and light chain isotype, or using MoAbs to each human IgG subclass. Neutralizing activity was measured as the inhibition of lyIFN antiviral activity for Vervet monkey cells challenged with Semliki Forest Virus. Among antibody-positive patients, 12% produced IgM coincident with IgG, and 25% produced IgA coincident with IgG. Thus, antibody responses in patients treated with lyIFN are not exclusively of IgG class. The predominant lyIFN-specific subclasses were IgG1 and IgG3, which occurred in 70% and 83% of patients, respectively. An IgG4 response was detected in two patients who also had antibody of other isotypes; no IgG2 antibody was detected in any patient. Antibodies were not IgG subclass-restricted, a trend which was more pronounced in patients having neutralizing antibody than non-neutralizing antibody. Light chain molecules of lyIFN-specific antibody were of both kappa and lambda isotypes, with kappa chains occurring most frequently. Among patients having non-neutralizing antibodies, monotypic light chains occurred in 65% of the patients, whereas no patient with neutralizing antibody had monotypic light chain antibody. Sera from 599 normal human volunteers were assayed for antibody, and seven were found to be immunoreactive to lyIFN. Only one serum of the seven was positive for neutralizing activity.