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.


METHODS
The cross-sectional study included 148 MS (84 treatment naive and 64 treated), 87 CIS, 42 OIND, and 96 HCs. Longitudinal study included 94 MS pretreatment and after 1 year of therapy with IFN-β, glatiramer acetate (GA), or natalizumab. sIFNAR2 serum levels were measured by a quantitative ELISA developed and validated in our laboratory.


RESULTS
Naive MS and CIS patients showed significantly lower sIFNAR2 levels than HCs and OIND patients. The sensitivity and specificity to discriminate between MS and OIND, for a sIFNAR2 cutoff value of 122.02 ng/mL, were 70.1%, and 79.4%, respectively. sIFNAR2 increased significantly in IFN-β-treated patients during the first year of therapy in contrast to GA- and natalizumab-treated patients who showed non-significant changes.


CONCLUSIONS
The results suggest that sIFNAR2 could be a potential diagnostic biomarker for MS.
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
Teresa
T
Órpez-Zafra
Departamento de Farmacología y Pediatría, Facultad de Medicina, Instituto de Biomedicina de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.
Jose
J
Pavía
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
Isaac
I
Hurtado-Guerrero
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain/Red Española de Esclerosis Múltiple (REEM).
Maria J
MJ
Pinto-Medel
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
Jose Luis
JL
Rodriguez Bada
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
Patricia
P
Urbaneja
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain/Red Española de Esclerosis Múltiple (REEM).
Margarita
M
Suardíaz
Servicio de Inmunología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain/Red Española de Esclerosis Múltiple (REEM).
Luisa M
LM
Villar
Department de Neurología-Neuroinmunología, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain/Red Española de Esclerosis Múltiple (REEM).
Manuel
M
Comabella
Department de Neurología-Neuroinmunología, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain/Red Española de Esclerosis Múltiple (REEM).
Xavier
X
Montalban
Servicio de Neurología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain/Red Española de Esclerosis Múltiple (REEM).
Jose C
JC
Alvarez-Cermeño
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain/Red Española de Esclerosis Múltiple (REEM).
Laura
L
Leyva
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain/Red Española de Esclerosis Múltiple (REEM).
Óscar
Ó
Fernández
Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain/Red Española de Esclerosis Múltiple (REEM).
Begoña
B
Oliver-Martos
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D000069442:Natalizumab / Q000627:therapeutic use; D011237:Predictive Value of Tests; D053633:Receptor, Interferon alpha-beta / Q000097:blood*; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; C508033:IFNAR2 protein, human; D007155:Immunologic Factors; D000069442:Natalizumab; D053633:Receptor, Interferon alpha-beta; D000068717:Glatiramer Acetate; D016899:Interferon-beta
Multiple sclerosis; biomarker; diagnosis; soluble interferon beta receptor