Decreased Type I Interferon Receptor-Soluble Isoform in Antiretroviral-Treated HIV-Positive Children

Abstract

We developed a real-time PCR assay to simultaneously measure the mRNA level of type I interferon (IFN) receptor (IFNAR) components in peripheral blood cells of children with chronic immune stimulation due to HIV infection. All patients were undergoing antiretroviral therapy and were divided into two groups on the basis of the induction of MxA mRNA, a marker of type I IFN bioactivity. We found that IFNAR-2 subunit mRNA was higher than that of the IFNAR-1 subunit, that the mRNA for the IFNAR-2.2 functional isoform was more expressed than that for the truncated IFNAR-2.1 isoform, and both were much more represented than that of the IFNAR-2.3 soluble isoform. We also demonstrated that soluble isoform mRNA was significantly diminished in the subgroup of patients with MxA mRNA below the cutoff value (determined as the 99th percentile of MxA measured in healthy controls). These results suggest that downregulation of the soluble receptor isoform, which would not compete with the functional isoform for binding to the target cytokine, would give type I IFN, eventually induced in these patients in the case of viral reactivation, the opportunity to promptly exert its antiviral activity.

Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients

“…Up to now, only few studies have investigated the role of all IFNAR components in human disease or under conditions of receptor stimulation and, to the best of our knowledge, a single work had previously analyzed the expression of all the different isoforms of IFNAR2 at the same time [176]. In order to address this question, our group has developed a Real-Time PCR assay that measures concomitantly IFNAR1 and IFNAR2 subunits mRNA and the three IFNAR2 isoforms [177]. After validation of the technique in terms of specificity and reproducibility, we used it to evaluate IFNAR gene expression in PBL of MS patients naïve for therapy and undergoing long-term treatment with IFN-.…”

Increase of IFNAR1 Messenger RNA in Myxovirus-protein-A-induced Multiple Sclerosis Patients to Oppose Loss of Protein Receptor

“…36,37 If we consider the rather low number of IFNAR molecules on the cell surface, 12 especially on lymphocytes, 38 values is rather wide, indicating that it is possible to find higher levels of soluble receptor in the sera of a few samples. 40 We then used this laboratory test to quantify mRNA expression for all IFNAR components in a group of long-term IFN-β-treated MS patients selected among those undergoing routine MxA determination in our laboratory. Their IFNAR mRNA levels were compared with those of a control group and of therapy-naïve MS patients in order to ascertain receptor modulation during prolonged receptor stimulation by IFN-β.…”

Which NK cell populations mark the high burden of CMV present in all HIV patients beginning ART in Indonesia?

“…The latter can regulate the biological activity of IFNα/β through competition at high concentrations and stabilisation at lower concentrations [ 15 ]. Levels of sIFNRα/β may be downregulated in HIV patients with poor control of HIV on ART—potentially increasing the antiviral activity of IFNα/β [ 16 ]. Associations with CMV and NK cell activation have not been considered in this context.…”