IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a.
We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a (Roceron-A), Hoffmann La-Roche, Basel, Switzerland) three times weekly for periods of 8-16 weeks with or without a drug-free 4-12-week intermission. Additionally, 10 patients were investigated prospectively; 7 received 1.5-6 x 10(6) IU IFN-alpha2a three times weekly for 12 months, and 3 received placebo. Binding antibodies were tested by molecular size and protein G affinity chromatography using 125I-IFN-alpha2a. Neutralizing activities were tested by antiviral neutralization bioassay. IgG antibodies were detected in 24 of 34 IFN-alpha2a-treated patients (71%). Significantly higher anti-IFN-alpha levels were observed in patients who after discontinuation were readministered IFN-alpha2a (p < 0.02). Three of the IFN-alpha2a-treated patients in the prospective study had high and 1 had low antibody titers. Neutralizing antibody titers were high against IFN-alpha2a and IFN-alpha2c and low against lymphoblastoid and leukocyte IFN-alpha. Impaired clinical responses were observed in antibody-positive patients (p < 0.01). The development of neutralizing anti-IFN-alpha antibodies in patients with AMD during recombinant human IFN-alpha therapy may explain the often poor clinical effect of IFN-alpha treatment.
Ross
Christian
C
Institute for Inflammation Research, Rigshospitalet University Hospital, Copenhagen, Denmark.
Engler
Claus Bødker
CB
Sander
Birgit
B
Bendtzen
Klaus
K
D000906:Antibodies / Q000097:blood*; D003429:Cross Reactions; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D007700:Kinetics; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D009500:Neutralization Tests; D011994:Recombinant Proteins; D012189:Retrospective Studies
D000906:Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins