Resistance to recombinant alpha interferon therapy in idiopathic mixed cryoglobulinemia: reinduction of remission by natural alpha interferon both in antibody-positive and -negative patients.
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.
Casato
M
M
Department of Clinical Medicine, University of Roma, La Sapienza, Italy.
Antonelli
G
G
Maggi
F
F
Pucillo
L P
LP
Di Lullo
L
L
Leoni
M
M
Currenti
M
M
Dianzani
F
F
Bonomo
L
L
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
D000906:Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins