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Netrin-1: a new player in multiple sclerosis pathogenesis?

AuthorsMulero, Patricia; Cordova, Claudia; Gutiérrez, Beatriz; Martín, Rubén ; Hernández, Marita ; Muñoz, Juan Carlos; Nieto, María Luisa ; Téllez, Nieves
Issue Date2015
CitationECTRIMS (2015)
Abstract[Background]: Netrin-1 is a secreted protein that regulates axon guidance and glial cell migration. In the experimental autoimmune encephalomyelitis (EAE) model, several reports indicate that netrin-1 reduces the levels of pro-inflammatory mediators in the blood and that stabilizes the blood¿brain barrier limiting the entrance of the immune cells from the periphery to the central nervous system Tough these observations could suggest an involvement of Netrine-1 in the Multiple Sclerosis (MS) pathogenesis, the behaviour of this molecule have never been demonstrated in humans. [Objective]: to determinate serum levels of netrin-1 in a cohort of MS patients and compare it with a control group (CG). Secondly, to study the relationship between serum netrin-1 levels with clinical inflammatory activity. [Methods]: a total of 100 MS patients (%female: 63; Age, mean±SD: 42±11.5) (%Clinically Isolated Syndrome (CIS): 6; %Relapsing-Remitting MS (RRMS): 58; %Primary-Progressive MS (PPMS): 13; %Secondary Progressive MS (SPMS): 23) and 50 GC (%female: 46; Age, mean±SD: 57±11.3) were included. Ten RRMS patients were evaluated during a relapse of the disease (RRMSr) and longitudinally 2 months later. Netrin-1 levels were measured in serum samples using a quantitative ELISA kit from Cusabio Biotech (Wuhan, China), according to the manufacturer¿s instructions. The minimal limit of detection was 7.81 pg/ml. [Results]: MS patients showed statistically significant lower netrin-1 levels compared to CG (MS (mean±SD): 511.62±209.30; CG: 748.32±103.24) (p<0.005). Remarkably, this difference was more pronounced in RRMSr who showed the lowest protein level (304.4±107.07) that remaining significantly decreased two months later. We did not found statistically significant differences in MS netrine-1 levels according to age (p=0.15), gender (p=0.07), disease subtype (p=0.63), MS onset (p=0.27), Expanded Disability Status Scale (p=0.65), Multiple Sclerosis Severity Score (p=0.23), immunomodulatory therapies (p=0.07) or relapses number in last two years (p=0.57). [Conclusion]: Our data showed that serum netrin-1 levels are decreased in MS patients, particularly during a relapse of the disease. This would be in agreement with previous reports in EAE models suggesting an anti-inflammatory effect of the netrin-1 in MS.
DescriptionResumen del póster presentado al 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, celebrado en barcelona (España) del 7 al 10 de octubre de 2015.-- et al.
Appears in Collections:(IBGM) Comunicaciones congresos
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