Recombinant soluble type I interferon receptor exerts antiviral activity by inducing proteins related to autophagy.

Unlabelled: The soluble type I IFN receptor (sIFNAR2) is produced by alternative splicing and is present in body fluids. Although it can modulate IFN-ß activity, its biological role remains unknown.

Methods: An in-silico study was conducted to compare the structure of recombinant human soluble IFNAR2 (r-sIFNAR2) with its native form.

Natalizumab-immunogenicity evaluation in patients with infusion related events or disease exacerbations.

Introduction: Natalizumab is a biologic drug for relapsing-remitting multiple sclerosis that may induce the generation of anti-drug antibodies in some patients. Anti-natalizumab antibodies (ANA) increase the risk of adverse events and reduce efficacy, being useful biomarkers for monitoring treatment response.

Methods: Retrospective observational study including MS patients treated with natalizumab that experienced infusion-related events (IRE) or disease exacerbations (DE).

Soluble Receptor Isoform of IFN-Beta (sIFNAR2) in Multiple Sclerosis Patients and Their Association With the Clinical Response to IFN-Beta Treatment.

Purpose: Interferon beta receptor 2 subunit (IFNAR2) can be produced as a transmembrane protein, but also as a soluble form (sIFNAR2) generated by alternative splicing or proteolytic cleavage, which has both agonist and antagonist activities for IFN-β. However, its role regarding the clinical response to IFN-β for relapsing-remitting multiple sclerosis (RRMS) is unknown. We aim to evaluate the short-term effects and after 6 and 12 months of IFN-β therapy on sIFNAR2 production and their association with the clinical response in MS patients.

Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation.

Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis.

Cross-reactivity of antibodies against interferon beta in multiple sclerosis patients and interference of the JAK-STAT signaling pathway.

Interferon beta (IFNβ) therapy has immunogenic properties and induces the development of neutralizing antibodies (NAbs). From the extensive literature focused in the development of NAbs in multiple sclerosis (MS) patients, their ability to cross-react has been deficiently evaluated, despite having important consequences in the clinical practice. Here, the relation between the cross-reactivity and the NAbs titers has been evaluated in MS patients, by inhibition of the antiviral activity of IFNβ by bioassay and through the interference with the activation of the IFNß pathway (JAK-STAT), by phosphoflow.

Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß.

Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway.

Decreased soluble IFN-β receptor (sIFNAR2) in multiple sclerosis patients: A potential serum diagnostic biomarker.

Background: The soluble isoform of the interferon-β (IFN-β) receptor (sIFNAR2) could modulate the activity of both endogenous and systemically administered IFN-β. Previously, we described lower serum sIFNAR2 levels in untreated multiple sclerosis (MS) than in healthy controls (HCs).

Objective: To assess sIFNAR2 levels in a new cohort of MS patients and HCs, as well as in patients with clinically isolated syndrome (CIS) and with other inflammatory neurological disorders (OIND) and to assess its ability as a diagnostic biomarker.

Development and validation of an ELISA for quantification of soluble IFN-β receptor: assessment in multiple sclerosis.

Aim: The soluble isoform of the IFN-β receptor (sIFNAR2) can bind IFN-β and modulate its activity, although its role in autoimmune diseases remains unknown.

Methods: A recombinant human sIFNAR2 protein was cloned, expressed and purified after which we developed and validated an ELISA for its quantification in human serum. Serum sIFNAR2 were assessed in multiple sclerosis (MS) patients and healthy controls.