Human IRF2 ELISA Matched Antibody Pair

Interferon regulatory factors (IRF) 1 and 2 are DNA-binding proteins which control interferon (IFN) gene expression. IRF1 functions as an activator for IFN and IFN-inducible genes, whereas IRF2 represses the action of IRF1. Expression of the two regulatory genes is itself IFN-inducible. Because therapeutic responses of chronic myeloid leukaemia (CML) patients to IFN-alpha may be determined by intracellular levels of these two mutually antagonistic transcription factors, we have devised a competitive reverse-transcription polymerase chain reaction (RT-PCR) assay which provides an estimate of the ratio of IRF1 to IRF2 expression in a given cell population. Analysis of peripheral blood leucocytes from 25 normal individuals showed that the IRF1:IRF2 ratio varied between 1.13 and 2.30 (mean +/- s.d. 1.49 +/- 0.33). Similar values were obtained for normal bone marrow specimens, with no significant difference between CD34(+) and CD34(-) cells. In contrast, the IRF1:IRF2 ratio in leucocytes from CML patients showed a much wider variation (0.53-5.11). Eleven out of 130 patients in chronic phase had ratios above the normal range, whereas none of the 33 blast crisis samples had a ratio >2.5. Analysis of diagnostic specimens in 59 CML patients treated subsequently with IFN-alpha showed a high IRF1:IRF2 ratio of 5.11 in one of two patients who became complete responders; all the 53 patients with minimal or no cytogenetic response had ratios below 2.5. In a separate series of 97 CML patients studied after IFN-alpha therapy a highly significant correlation was found between the IRF1:IRF2 ratio and both the cytogenetic and the molecular response tie low concentration of BCR-ABL transcripts) to treatment: 53 out of 115 prospectively analysed samples of good cytogenetic responders had ratios above 2.0, as opposed to only 13 out of 91 samples from poor responders (P < 0.0001; chi(2) test). We conclude that a high ratio of IRF1/IRF2 expression may be associated with good cytogenetic and molecular response to IFN-alpha in CML.

The immune response against viral pathogens include specific and non specific mechanisms. Cytokines are peptides which can play a role in the non specific immunity. Type I interferons (IFN alpha/beta) are the most effective antiviral cytokines. Interferons alpha are represented by a large familly of structurally related genes while the IFN beta is encoded by a single gene. Type I interferon genes are located on the chromosome 9, and are segregated in a "modern" and an "ancestral" group with distinctive effects onto the cells. Type I interferons consist of 5 alpha helices, 4 of which are closely held together. Type I interferons receptor is a member of the class II cytokine receptor familly. It is a heterodimer composed of polypeptidic chains naimed IFNAR-1 and IFNAR-2. The type I interferons inducers are viruses, inactivated Viruses and certain synthetic molecules. The molecular mechanisms of the induction of IFN beta have been extensively described whereas the factors that play a role in the regulation of IFN alpha are not so well characterized. Two regulating domains located on the IFN beta gene promotor are involved. The activation of these regulating domains leads to adverse effects by interacting with two intracellular factors (IRF1 and IRF2). IRF1 enhances the synthesis of IFN beta but other pathways may be involved as well. The different IFN alpha sub-types have not only synergistic but also antagonistic effects. The synthesis of the different subtypes depends on cell lines and IFN alpha inducers. The N terminal part of IFN alpha is a major determinant in the diversity of the biological effects of IFN alpha subtypes which probably involve changes of the conformation of the type I receptor resulting from interactions between the receptor and its ligand. The type I interferons confer resistance to viruses, especially by enhancing the synthesis of intracellular antiviral proteins.