Contributions
Abstract: P855
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: There is a need to identify response biomarkers that help the choice of treatment that will be most effective for MS patients. The soluble IFNß receptor (sIFNAR2) is an isoform generated by alternative splicing, that can be detected in serum and is able to modulate the activity of both endogenous and systemically administered IFNb.
We previously described that untreated-MS patients showed significantly lower serum levels of sIFNAR2 than healthy controls, in two independent cohorts, so it was proposed as diagnostic biomarker. Now, our aim is to assess sIFNAR2 levels as IFNß response biomarker as well as to evaluate its relationship with other clinical variables.
Methods: The longitudinal study included 51 MS patients (basal, 6 and 12 months after IFNß treatment onset) classified as responders (R) and non responders (NR) according to the Rio Score. Additionally, 12 MS patients were analyzed during the relapse and in the remission period. For the clinical form, 143 relapsing remitting, 43 secondary progressive and 12 primary progressive were analyzed.
Quantification of sIFNAR2 was performed by ELISA developed and validated in our laboratory. Each assay included a standard curve, 2 quality controls and a negative control. Non parametric tests were used.
Results: Before the onset of treatment, NR patients had significantly lower levels of sIFNAR2 compare to R patients (p=0.026). Then, a logistic regression analysis showed that patients with basal sIFNAR2 levels lower than 43.2ug/ml have OR of 5.1 (p=0.012 CI [1.42-18.25]) of being a non-responders to IFNb treatment. The model was adjusted for possible confounding variables such as sex, age and evolution time. NR patients increased sIFNAR2 levels after 6 months of treatment (p= 0.010), while sIFNAR2 levels while levels remain stable in R patients.
On the other hand, elevated levels of sIFNAR2 were observed in patients during the relapse compared with the same patient in remission (p=0.002). Regarding the clinical form, PP had elevated sIFNAR2 compared to RR and SP (p= 0.042, p= 0.010).
Conclusions: Basal levels of sIFNAR2 is a predictive value of response to IFNb treatment and could have clinical applicability at the time of choosing the treatment. The lower basal levels of sIFNAR2 in non responders patients are restored six months after IFNb treatment and reach similar values to responders patients. sIFNAR2 could be involved in the pathogenesis of MS and IFNb treatment could modulate its levels.
Disclosure: This work was supported by grants from Consejería de Igualdad, Salud y Políticas Sociales (Junta de Andalucía) to B. Oliver-Martos (PI-0267-2013) and by grant from the Instituto de Salud Carlos III co-founded by Fondo Europeo de Desarrollo Regional (FEDER) to B. Oliver-Martos (PI13/00927).
Maria Jesus Pinto-Medel: nothing to disclose
Isaac Hurtado-Guerrero: nothing to disclose
Ana Alonso: nothing to disclose
Jose Luis Rodriguez Bada: nothing to disclose
Patricia Urbaneja: nothing to disclose
Oscar Fernández: nothing to disclose
Laura Leyva: nothing to disclose
Begoña Oliver-Martos: nothing to disclose
Abstract: P855
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: There is a need to identify response biomarkers that help the choice of treatment that will be most effective for MS patients. The soluble IFNß receptor (sIFNAR2) is an isoform generated by alternative splicing, that can be detected in serum and is able to modulate the activity of both endogenous and systemically administered IFNb.
We previously described that untreated-MS patients showed significantly lower serum levels of sIFNAR2 than healthy controls, in two independent cohorts, so it was proposed as diagnostic biomarker. Now, our aim is to assess sIFNAR2 levels as IFNß response biomarker as well as to evaluate its relationship with other clinical variables.
Methods: The longitudinal study included 51 MS patients (basal, 6 and 12 months after IFNß treatment onset) classified as responders (R) and non responders (NR) according to the Rio Score. Additionally, 12 MS patients were analyzed during the relapse and in the remission period. For the clinical form, 143 relapsing remitting, 43 secondary progressive and 12 primary progressive were analyzed.
Quantification of sIFNAR2 was performed by ELISA developed and validated in our laboratory. Each assay included a standard curve, 2 quality controls and a negative control. Non parametric tests were used.
Results: Before the onset of treatment, NR patients had significantly lower levels of sIFNAR2 compare to R patients (p=0.026). Then, a logistic regression analysis showed that patients with basal sIFNAR2 levels lower than 43.2ug/ml have OR of 5.1 (p=0.012 CI [1.42-18.25]) of being a non-responders to IFNb treatment. The model was adjusted for possible confounding variables such as sex, age and evolution time. NR patients increased sIFNAR2 levels after 6 months of treatment (p= 0.010), while sIFNAR2 levels while levels remain stable in R patients.
On the other hand, elevated levels of sIFNAR2 were observed in patients during the relapse compared with the same patient in remission (p=0.002). Regarding the clinical form, PP had elevated sIFNAR2 compared to RR and SP (p= 0.042, p= 0.010).
Conclusions: Basal levels of sIFNAR2 is a predictive value of response to IFNb treatment and could have clinical applicability at the time of choosing the treatment. The lower basal levels of sIFNAR2 in non responders patients are restored six months after IFNb treatment and reach similar values to responders patients. sIFNAR2 could be involved in the pathogenesis of MS and IFNb treatment could modulate its levels.
Disclosure: This work was supported by grants from Consejería de Igualdad, Salud y Políticas Sociales (Junta de Andalucía) to B. Oliver-Martos (PI-0267-2013) and by grant from the Instituto de Salud Carlos III co-founded by Fondo Europeo de Desarrollo Regional (FEDER) to B. Oliver-Martos (PI13/00927).
Maria Jesus Pinto-Medel: nothing to disclose
Isaac Hurtado-Guerrero: nothing to disclose
Ana Alonso: nothing to disclose
Jose Luis Rodriguez Bada: nothing to disclose
Patricia Urbaneja: nothing to disclose
Oscar Fernández: nothing to disclose
Laura Leyva: nothing to disclose
Begoña Oliver-Martos: nothing to disclose