title: Resistance to recombinant alpha interferon therapy in idiopathic mixed cryoglobulinemia: reinduction of remission by natural alpha interferon both in antibody-positive and -negative patients.
abstract: A subset of patients treated with recombinant interferon alpha-2a (rIFN-alpha 2a) for idiopathic mixed cryoglobulinemia (IMC) developed clinical resistance to therapy after a sustained response. Neutralizing antibodies 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. rIFN-alpha 2a neutralizing antibodies appeared in serum samples of the former three patients 1, 5 and 6 months before evidence for clinical resistance, respectively. Antibody titres to rIFN-alpha 2a were consistently higher than those to natural interferon (nIFN). In the fourth patient with clinical resistance, neutralizing antibodies could not be detected by a very sensitive bioassay in any of several serum samples taken before and after relapse. All the four patients could be reinduced into remission by the administration of nIFN-alpha. These data indicate that mechanisms other than the production of neutralizing antibodies can mediate acquired resistance to IFN therapy. Furthermore, both antibody-related and -unrelated resistance can be overcome by switching to different species of IFN-alpha.
authors.affiliation: Department of Clinical Medicine, University of Roma, La Sapienza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Casato
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
authors.forename: F
authors.initials: F
authors.lastname: Maggi
authors.forename: L P
authors.initials: LP
authors.lastname: Pucillo
authors.forename: L
authors.initials: L
authors.lastname: Di Lullo
authors.forename: M
authors.initials: M
authors.lastname: Leoni
authors.forename: M
authors.initials: M
authors.lastname: Currenti
authors.forename: F
authors.initials: F
authors.lastname: Dianzani
authors.forename: L
authors.initials: L
authors.lastname: Bonomo
mesh_terms: D000906:Antibodies / Q000097:blood; D003449:Cryoglobulinemia / Q000276:immunology / Q000628:therapy*; D004351:Drug Resistance; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D009500:Neutralization Tests; D011994:Recombinant Proteins; D012008:Recurrence; D012074:Remission Induction
chemical_list: D000906:Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins