RESISTANCE TO RECOMBINANT ALPHA-INTERFERON THERAPY IN IDIOPATHIC MIXED CRYOGLOBULINEMIA - REINDUCTION OF REMISSION BY NATURAL ALPHA-INTERFERON BOTH IN ANTIBODY-POSITIVE AND ANTIBODY-NEGATIVE PATIENTS

A subset of patients treated with recombinant interferon alpha-2a (rIF N-alpha 2a) for idiopathic mixed cryoglobulinemia (IMC) developed clin ical resistance to therapy after a sustained response. Neutralizing an tibodies to rIFN-alpha 2a were found in the sera of three out of four such patients, and in none of the patients who remained responsive to treatment. rlFN-alpha 2a neutralizing antibodies appeared in serum sam ples of the former three patients 1, 5 and 6 months before evidence fo r clinical resistance, respectively. Antibody titres to rlFN-alpha 2a were consistently higher than those to natural interferon (nIFN). lit the fourth patient with clinical resistance, neutralizing antibodies c ould not be detected by a very sensitive bioassay in any of several se rum samples taken before and after relapse. All the four patients coul d be reinduced into remission by the administration of nlFN-alpha. The se data indicate that mechanisms other than the production of neutrali zing antibodies can mediate acquired resistance to IFN therapy. Furthe rmore, both antibody-related and -unrelated resistance can be overcome by switching to different species of IFN-alpha.