TY - JOUR

T1 - IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

AU - Ross, Christian

AU - Engler, Claus Bødker

AU - Sander, Birgit

AU - Bendtzen, Klaus

PY - 2002/4/1

Y1 - 2002/4/1

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.1089/10799900252952208

DO - http://dx.doi.org/10.1089/10799900252952208

M3 - Journal article

VL - 22

SP - 421

EP - 426

JO - Journal of Interferon and Cytokine Research

JF - Journal of Interferon and Cytokine Research

SN - 1079-9907

IS - 4

ER -