What roles have anti-interferon antibodies in physiology and pathology?

Until recently the generation of antibodies to interferons (IFNs) was considered an unlikely event, while it is now clear that natural interferons (except IFN-beta) are practically nonimmunogenic, although recombinant interferons give rise to antibodies in about 30% of patients with occasional clinical complications. By realizing that normal individuals display spontaneously traces of IFN autoantibodies, in this review it is suggested that (if immunotherapy has to succeed) new generations of recombinant proteins should be the least antigenic as possible.