Early blood neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels associate with different disease courses of myelin oligodendrocyte glycoprotein-associated disease in children

Author:

Horellou Philippe1ORCID,Flet-Berliac Lorraine1,Leroy Carole1,Giorgi Laetitia1,Joly Candie1,Desjardins Delphine1,Chrétien Pascale23,Hacein-Bey-Abina Salima23,Le Grand Roger1,Deiva Kumaran145

Affiliation:

1. Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, CEA, INSERM , Le Kremlin Bicêtre 94276 , France

2. Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Saclay, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris , Le-Kremlin-Bicêtre 94275 , France

3. Unité des technologies Chimiques et Biologiques pour la Santé, Université de Paris, CNRS, INSERM, UTCBS , Paris F-75006 , France

4. Pediatric Neurology Department, Assistance Publique-Hôpitaux de Paris, Paris-Saclay University Hospitals, Bicêtre Hospital , Le Kremlin Bicêtre 94270 , France

5. National Referral Center for Rare Inflammatory and Auto-Immune Brain and Spinal Diseases (MIRCEM), AP-HP Le Kremlin Bicêtre 94270 , France

Abstract

AbstractAcquired demyelinating syndrome associated with myelin oligodendrocyte glycoprotein antibodies, named recently myelin oligodendrocyte glycoprotein-associated disease, represents >27% of this paediatric syndrome. Relapses occur in 40% of them, which may be associated with severe outcomes. Aiming to identify biomarker allowing to predict relapse, we measured both myelin oligodendrocyte glycoprotein antibodies and neurofilament light chain levels in blood samples of patients that are known to reflect axonal injuries in neurological diseases including demyelinating autoimmune disorders. Three groups of patients were selected: relapsing myelin oligodendrocyte glycoprotein-associated disease (n = 8), non-relapsing myelin oligodendrocyte glycoprotein-associated disease (n = 7) and control patients with non-inflammatory neurological diseases (n = 12). Neurofilament light chain concentrations were measured in plasma of these three groups of patients using the high-sensitivity single-molecule array method at onset of the disease and 6 months later. At onset of the disease, we found that levels of neurofilament light chain in blood of non-relapsing patients were significantly higher than in control patients (means: 98.36 ± 22.66 versus 12.47 ± 2.47 pg/mL, **P < 0.01, Kruskal–Wallis test). The mean neurofilament light chain value in relapsing patients (82.16 ± 38.41 pg/mL) was not significantly different from that in non-relapsing and in control patients. Plasma myelin oligodendrocyte glycoprotein antibody levels were 2.5-fold higher in relapsing than in non-relapsing patients without reaching significance (means: 15.26 ± 4.87 versus 5.96 ± 1.13; two-tailed Mann–Whitney U-test P = 0.119). Plasma neurofilament light chain correlated significantly with myelin oligodendrocyte glycoprotein antibody levels in relapsing (two-tailed Spearman r = 0.8, P = 0.0218) but not in non-relapsing (two-tailed Spearman r = 0.17, P = 0.71). Interestingly, the ratio of neurofilament light chain-to-myelin oligodendrocyte glycoprotein antibodies was significantly lower in relapsing than in non-relapsing patients (means: 5.19 ± 1.61 versus 21.87 ± 6.13; two-tailed Mann–Whitney U-test P = 0.014). These findings suggest that measuring both neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels in patients at onset of demyelinating disease could predict relapse of myelin oligodendrocyte glycoprotein-associated disease.

Funder

Institut National de la Santé et de la Recherche Médicale

INSERM

Assistance Publique-Hôpitaux de Paris

AP-HP

Publisher

Oxford University Press (OUP)

Subject

Neurology,Cellular and Molecular Neuroscience,Biological Psychiatry,Psychiatry and Mental health

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