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oai:repisalud.isciii.es:20.500.12105/185202024-11-28T14:53:20Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16969
Repisalud author Aliaga-Gaspar, Pablo author Hurtado-Guerrero, Isaac author Ciano-Petersen, Nicolas Lundahl author Urbaneja, Patricia author Brichette-Mieg, Isabel author Reyes, Virginia author Rodriguez-Bada, Jose Luis author Alvarez-Lafuente, Roberto author Arroyo, Rafael author Quintana, Ester author Ramió-Torrentà, Lluis author Alonso, Ana author Leyva, Laura author Fernández, Oscar author Oliver-Martos, Begoña authoraffiliation [Aliaga-Gaspar,P; Hurtado-Guerrero,I; Ciano-Petersen,NL; Urbaneja,P; Brichette-Mieg,I; Reyes,V; Rodriguez-Bada,JL; Alonso,A; Leyva,L; Oliver-Martos,B] Neuroimmunology and Neuroinflammation Group, Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica (UGC) Neurociencias, Hospital Regional Universitario de Málaga, Málaga, Spain. [Aliaga-Gaspar,P] Facultad de Medicina, Universidad de Málaga, Málaga, Spain. [Hurtado-Guerrero,I] Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, Copenhagen Biocentre, University of Copenhagen, Copenhagen, Denmark. [Ciano-Petersen,NL; Urbaneja,P; Reyes,V; Alonso,A; Oliver-Martos,B] Red Andaluza de Investigación Clínica y Traslacional en Neurología (Neuro-Reca), Málaga, Spain. [Alvarez-Lafuente,R] Grupo de Investigació n de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [Alvarez-Lafuente,R; Quintana,E; Ramió-Torrentà,L; Leyva,L; Oliver-Martos,B] Red Española de Esclerosis Múltiple (REEM), Madrid, Spain. [Arroyo,R] Servicio de Neurología, Hospital Universitario Quirónsalud, Madrid, Spain. [Quintana,E; Ramió-Torrentà,L] Servicio de Neurología, Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain. [Ramió-Torrentà,L] Girona Biomedical Research Institute (IDIBGI), Girona, Spain. [Ramió-Torrentà,L] Medical Sciences Department, University of Girona, Girona, Spain. [Fernández,O] Departmento de Farmacología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain. [Oliver-Martos,B] Departamento de Biologéa Celular, Genética y Fisiología, Área de Fisiología, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain. 2024-02-19T15:32:24Z 2024-02-19T15:32:24Z 2021-12-16 http://hdl.handle.net/10668/4025 http://hdl.handle.net/20.500.12105/18520 34975865 10.3389/fimmu.2021.778204 1664-3224 Frontiers in Immunology 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-b. However, its role regarding the clinical response to IFN-b for relapsing-remitting multiple sclerosis (RRMS) is unknown. We aim to evaluate the in vitro short-term effects and after 6 and 12 months of IFN-b therapy on sIFNAR2 production and their association with the clinical response in MS patients. Methods: Ninety-four RRMS patients were included and evaluated at baseline, 6 and 12 months from treatment onset. A subset of 41 patients were classified as responders and non-responders to IFN-b therapy. sIFNAR2 serum levels were measured by ELISA. mRNA expression for IFNAR1, IFNAR2 splice variants, MxA and proteases were assessed by RT-PCR. The short-term effect was evaluated in PBMC from RRMS patients after IFN-b stimulation in vitro. Results: Protein and mRNA levels of sIFNAR2 increased after IFN-b treatment. According to the clinical response, only non-responders increased sIFNAR2 significantly at both protein and mRNA levels. sIFNAR2 gene expression correlated with the transmembrane isoform expression and was 2.3-fold higher. While MxA gene expression increased significantly after treatment, IFNAR1 and IFNAR2 only slightly increased. After short-term IFN-b in vitro induction of PBMC, 6/7 patients increased the sIFNAR2 expression. Conclusions: IFN-b administration induces the production of sIFNAR2 in RRMS and higher levels might be associated to the reduction of therapeutic response. Thus, levels of sIFNAR2 could be monitored to optimize an effective response to IFN-b therapy. eng Alternative splicing Soluble receptors IFNAR Interferon beta Multiple sclerosis Empalme alternativo Receptor de interferones alfa y beta Interferón beta Esclerosis múltiple Soluble Receptor Isoform of IFN-Beta (sIFNAR2) in Multiple Sclerosis Patients and Their Association With the Clinical Response to IFN-Beta Treatment research article