Monitoring Patients Treated with Type1 Interferons: Potential Reporter Genes in Patient Leucocytes

Interferon-α/β (IFN-α/β) is increasingly used as antiviral and immunomodulatory therapies. Unfortunately, bioavailability varies with IFN species and mode of administration, and all IFN species are potentially immunogenic. Assays for antiviral activity (IFN) and antiviral neutralization (antibodies, NAb) have been used for some time to monitor patients on IFN biologicals. These assays require laborious titrations making them unsuitable for large-scale clinical use. Myxovirus A (MxA) is a resistance GTP-binding protein that is specifically induced by treatment with type 1 IFNs. For example, IFN-β-induced MxA in blood leucocytes has been used as a biomarker in IFN-β-treated patients with multiple sclerosis. However, the degree of specificity of MxA in this regard is unclear, and measurements of MxA protein and/or mRNA are not yet suitable for routine clinical use. In an attempt to find new and better reporter genes (and, hopefully, genes and gene products with proven specificity for IFN-α and -β), microarray screenings with U133A GeneChips (Affymetrix) were carried using human blood leucocytes and the human lung carcinoma cell line A549. We studied the simultaneous expression of 22,000 transcripts before and after exposure to human recombinant IFN-α and IFN-β and other antiviral and immunomodulatory cytokines. The results will be presented at the conference.