Sara Carta1, Alessadro Dinoto1, Marco Alfonso Narduc Capobianco2, Paola Valentino3, Marianna Lo Re3, Vanessa Chiodega1, Pierre Branger4, Bertrand Audoin5, Jennifer Aboab6, Caroline Papeix7, Nicolas Collongues8, Philippe Kerschen9, Zephir Helene10, Alain Creange11, Bertrand Bourre12, Eoin Flanagan13, Vyanka Redenbaugh13, Javier Villacieros-Álvarez14, Georgina Arrambide14, Alvaro Cobo-calvo14, Sergio Ferrari1, Romain Marignier15, Sara Mariotto1
1Department of Neuroscience, Biomedicine and Movement Sciences, Neurology Unit, University of Verona, 2Department of Neurology, S. Croce e Carle Hospital, Cuneo (Italy) and CRESM Biobank, Orbassano, Italy, 3Department of Neurology, University Hospital San Luigi, Regional Multiple Sclerosis Centre, Orbassano, Italy, 4Service de Neurologie, CHU de Caen Normandie, Caen, France., 5Department of Neurology, Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Aix Marseille University, 6Department of Internal Medecine, Centre Hospitalier National des Quinze-Vingts, 7Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Institut du Cerveau, CIC Neuroscience, ICM, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 8Service de Neurologie and CIC INSERM 1434, CHU de Strasbourg, 9Centre Hospitalier de Luxembourg, 10Department of Neurology, U 1172, CRC-SEP, University Hospital of Lille, 11Service de Neurologie, Centre de Ressources et de Compétences-Sclérose en Plaques, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Université Paris-Est Créteil, 12Department of Neurology, Rouen University Hospital, F-76000 Rouen, 13Department of Neurology, Department of Laboratory Medicine and Pathology, Rochester, United States, Mayo Clinic College of Medicine and Science, 14Centre d'Esclerosi Múltiple de Catalunya, (CEMCAT), Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Servei de Neurologia-Neuroimmunologia, 15Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation
Objective:
Aim of this study is to characterise the neuronal, axonal, and glial damage in seronegative NMOSD in comparison with AQP4+NMOSD
Background:
serum GFAP and NfL define disease activity in different neurological conditions. These biomarkers increase in patients with AQP4+NMOSD during clinical attacks, with contradictory results in seronegative-NMOSD.
Design/Methods:
patients with double (i.e. for AQP4 and MOG-Abs) seronegative-NMOSD and age-matched AQP4+NMOSD with available onset/relapse serum samples (i.e. obtained within 3 months) were retrospectively enrolled. Clinical and radiological data were collected. Serum NfL, GFAP, Tau and UCH-L1 levels were determined using an ultrasensitive paramagnetic bead-based enzyme-linked immunosorbent assay (SIMOA). Statistical analysis was performed using parametric and non-parametric tests and ROC analysis
Results:
27 seronegative-NMOSD and 24 AQP4+NMOSD patients were included. Median age at sampling was 36.2 years [IQR 27.0-49] with no statistical differences between groups. Most common syndromes at sampling in both seronegative-NMOSD and AQP4+NMOSD were myelitis (37% vs 54.2%) and optic neuritis (33.3% vs 37.5%). Median EDSS at sampling was 3.5 [IQR 2.5-7.0], with no significant difference between the two groups. Serum GFAP, Tau and UCH-L1 levels were significantly higher in AQP4+NMOSD compared to seronegative-NMOSD patients (median 304.1 vs 160.5 pg/mL p=0.005; median 24.8 vs 13.3 pg/mL, p= 0.002; and median 60 vs 37.3 pg/mL, p=0.021, respectively), as confirmed by ROC analysis, while NfL levels were similar (p=0.270). In the seronegative-NMOSD group, NfL and UCH-L1 levels correlated with EDSS at attack nadir (rho 0.438, p=0.032 and rho 0.429 p=0.036, respectively), while in the AQP4+NMOSD group this correlation was observed for NfL, UCH-L1, and GFAP levels (rho 0.745, p=0.010; rho 0.448, p=0.32, rho 525, p= 0.010, respectively).
Conclusions:
serum GFAP, Tau, and UCH-L1 levels discriminate between AQP4+NMOSD and seronegative-NMOSD. The different biomarkers profile suggests heterogeneity of diseases and provides useful data to improve our understanding of these diseases