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Natural autoantibodies (aAb) to IFN. |
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| Demonstration of natural aAb to IFN species in sera of healthy individuals has met with considerable difficulties. Despite the fact that human sera often suppress the antiviral activity of IFN, and even though IFN species may bind to IgG using immunoblotting techniques, specific Ab to IFN-alpha, IFN-beta and IFN-gamma are usually not the cause of this antiviral effect (1, 2). However, when testing sera from healthy blood donors for BAb to solute radiolabeled IFN-alpha, up to 10% are positive (3).
The existence of BAb in at least some of these individuals is testified by the finding of specific and high-avidity IFN-alpha BAb (Kd 1-100 pM) in pharmaceutically prepared human IgG pooled from large numbers of healthy individuals (4). The antiviral effect of IFN-alpha is also blocked by saturable binding to the Fab fragments of these IgG molecules. Accordingly, at least some of these BAb may be categorized as anti-IFN-alpha NAb as well. We have also investigated the presence of BAb/NAb to IFN-beta radiolabeled rin 2,450 blood donors; only 1 was positive (< 0.1%), and this serum also neutralised the antiviral effect of IFN-beta. Cited references: 1. Ross C, Hansen MB, Schyberg T, Berg K. Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFN-a2b and human IFN-g in healthy blood donors. Clin Exp Immunol 1990;82:57-62. 2. Hansen MB, Svenson M, Bendtzen K. Serum-induced suppression of interferon (IFN) activity. Lack of evidence for the presence of specific autoantibodies to IFN-alpha in normal human sera. Clin Exp Immunol 1992;88:559-62. 3. Bendtzen K, Ross C, Hansen MB, Svenson M. Natural and induced anti-cytokine antibodies. In: Ciliberto G, Savino R, editors. Cytokine inhibitors. New York: Marcel Dekker; 2000. p. 53-95. 4. Ross C, Svenson M, Hansen MB, Vejlsgaard GL, Bendtzen K. High avidity IFN-neutralising antibodies in pharmaceutically prepared human IgG. J Clin Invest 1995;95:1974-8. KB 2000 |
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