Analysis of Interferon-α2 Sequences in Human Genomic DNA

Gewert, Dirk R.; Salom, Caroline; Barber, Karen A.; Macbride, S. J.; Cooper, Herbert L.; Lewis, Alan P.; Wood, J C; Crowe, Sheila E.

doi:10.1089/jir.1993.13.227

Cited by 16 publications

(1 citation statement)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Merigan and colleagues [46] gave relatively large amounts (15)(16)(17)(18)(19)(20) of leucocyte IFN to immunosuppressed patients when they developed herpes zoster. Those who started treatment after a delay of more than 1 day from the time of appearance of vesicles had progressively more disseminated lesions and more post-herpetic pain than those who started IFN within 24 hours.…”

Section: Disseminated Herpes Zostermentioning

confidence: 99%

Cytokines in the treatment of virus infections

Finter

1994

Biotherapy

View full text Add to dashboard Cite

The interferon (IFN) system consists of both the formation of the various IFN proteins, and the diverse cellular responses which these induce: these result from the intracellular changes which follow their binding to a specific cell surface receptor. There is only a single human gamma, omega and beta IFN; in contrast, there are 13 closely related chemical species ("subtypes") of human alpha IFN, which are nevertheless chemically and biologically distinct. IFN preparations made from mass cultured human cells or by using recombinant DNA techniques are now readily available for clinical use. IFN have a major role in the defence of the body against virus infections. In acute virus infections, preformed exogenous IFN cannot be given soon enough to be of value. However, IFN-alpha and IFN-beta have proved of considerable value in some chronic virus infections, particularly chronic virus hepatitis and chronic papillomavirus infections. The doses routinely used are associated with both acute and chronic toxic side effects. Also, some patients form specific neutralising antibodies against the particular IFN preparation injected, which may abrogate all the benefits of the treatment. Nevertheless, IFN are now established as agents for use in routine medical practice.

show abstract

Section: Disseminated Herpes Zostermentioning

confidence: 99%

Cytokines in the treatment of virus infections

Finter

1994

Biotherapy

View full text Add to dashboard Cite

show abstract

Epitopes recognized by neutralizing therapy‐induced human anti‐interferon‐α antibodies are localized within the N‐terminal functional domain of recombinant interferon‐α2

Nolte¹,

Günther²,

Wussow³

1996

Eur J Immunol

View full text Add to dashboard Cite

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.

show abstract