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Epitopes recognized by neutralizing therapy-induced human anti-interferon-alpha antibodies are localized within the N-terminal functional domain of recombinant interferon-alpha 2.

作者信息

Nolte K U, Günther G, von Wussow P

机构信息

Dept. of Clinical Immunology, Medical School of Hannover, Germany.

出版信息

Eur J Immunol. 1996 Sep;26(9):2155-9. doi: 10.1002/eji.1830260929.

DOI:10.1002/eji.1830260929
PMID:8814261
Abstract

During prolonged recombinant interferon (rIFN)-alpha 2 therapy, a minority of patients develop high-titer neutralizing IFN-alpha antibodies. Sera from nine IFN-alpha antibody-positive patients were studied to characterize the specificity of anti-IFN-alpha neutralizing antibodies by their ability to inhibit the antiviral and antiproliferative activity of different rIFN-alpha subtypes and rIFN-alpha 1/alpha 2 hybrids. These therapy-induced antibodies (Tab) were compared with IFN-alpha-specific autoantibodies (Aab) from two patients with systemic lupus erythematosus who had never received any exogenous IFN-alpha. Although IFN-alpha subtypes are closely related in structure, Tab inhibited the antiviral activity of only recombinant (r)IFN-alpha 2 and rIFN-alpha 6, but not or slightly that of rIFN-alpha 1, -alpha 7, -alpha 8 and -alpha 14. Furthermore, of four different rIFN-alpha 1/alpha 2 hybrids tested, Tab inhibited only those which contained the N-terminal residues 17-64 of rIFN-alpha 2. Comparison of the primary sequences of neutralized and not neutralized subtypes suggests an epitope involving the residues 22-31 of IFN-alpha 2 is recognized. Thus, Tab block rIFN-alpha 2 by reacting with only one of two functional domains. In contrast, Aab possessed a broad specificity and neutralized both the antiviral and antiproliferative activity of rIFN-alpha 2, -alpha 6, -alpha 7, -alpha 8, and -alpha 14. They also neutralized all four rIFN-alpha 1/alpha 2 hybrids tested. These data demonstrate that Tab are highly specific for the therapeutic IFN-alpha subtype and specifically neutralize rIFN-alpha 2 by binding to its N-terminal functional domain.

摘要

相似文献

1
Epitopes recognized by neutralizing therapy-induced human anti-interferon-alpha antibodies are localized within the N-terminal functional domain of recombinant interferon-alpha 2.
Eur J Immunol. 1996 Sep;26(9):2155-9. doi: 10.1002/eji.1830260929.
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