Prognostic relevance of quantitative and longitudinal MOG antibody testing in patients with MOGAD: a multicentre retrospective study.


Journal

Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R

Informations de publication

Date de publication:
03 2023
Historique:
received: 21 08 2022
accepted: 06 11 2022
pubmed: 3 12 2022
medline: 17 2 2023
entrez: 2 12 2022
Statut: ppublish

Résumé

IgG antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) define a subset of associated disorders (myelin oligodendrocyte glycoprotein associated disorders (MOGAD)) that can have a relapsing course. However, information on relapse predictors is scarce. The utility of retesting MOG-IgG over time and measuring their titres is uncertain. We aimed to evaluate the clinical relevance of longitudinal MOG-IgG titre measurement to predict relapses in patients with MOGAD. In this retrospective multicentre Italian cohort study, we recruited patients with MOGAD and available longitudinal samples (at least one >3 months after disease onset) and tested them with a live cell-based assay with endpoint titration (1:160 cut-off). Samples were classified as 'attack' (within 30 days since a disease attack (n=59, 17%)) and 'remission' (≥31 days after attack (n=295, 83%)). We included 102 patients with MOGAD (57% adult and 43% paediatric) with a total of 354 samples (83% from remission and 17% from attack). Median titres were higher during attacks (1:1280 vs 1:640, p=0.001). Median onset titres did not correlate with attack-related disability, age or relapses. Remission titres were higher in relapsing patients (p=0.02). When considering the first remission sample available for each patient, titres >1:2560 were predictors of relapsing course in survival (log rank, p<0.001) and multivariate analysis (p<0.001, HR: 10.9, 95% CI 3.4 to 35.2). MOG-IgG seroconversion to negative was associated with a 95% relapse incidence rate reduction (incidence rate ratio: 0.05, p<0.001). Persistent MOG-IgG positivity and high remission titres are associated with an increased relapse risk. Longitudinal MOG-IgG titres could be useful to stratify patients to be treated with long term immunosuppression.

Sections du résumé

BACKGROUND
IgG antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) define a subset of associated disorders (myelin oligodendrocyte glycoprotein associated disorders (MOGAD)) that can have a relapsing course. However, information on relapse predictors is scarce. The utility of retesting MOG-IgG over time and measuring their titres is uncertain. We aimed to evaluate the clinical relevance of longitudinal MOG-IgG titre measurement to predict relapses in patients with MOGAD.
METHODS
In this retrospective multicentre Italian cohort study, we recruited patients with MOGAD and available longitudinal samples (at least one >3 months after disease onset) and tested them with a live cell-based assay with endpoint titration (1:160 cut-off). Samples were classified as 'attack' (within 30 days since a disease attack (n=59, 17%)) and 'remission' (≥31 days after attack (n=295, 83%)).
RESULTS
We included 102 patients with MOGAD (57% adult and 43% paediatric) with a total of 354 samples (83% from remission and 17% from attack). Median titres were higher during attacks (1:1280 vs 1:640, p=0.001). Median onset titres did not correlate with attack-related disability, age or relapses. Remission titres were higher in relapsing patients (p=0.02). When considering the first remission sample available for each patient, titres >1:2560 were predictors of relapsing course in survival (log rank, p<0.001) and multivariate analysis (p<0.001, HR: 10.9, 95% CI 3.4 to 35.2). MOG-IgG seroconversion to negative was associated with a 95% relapse incidence rate reduction (incidence rate ratio: 0.05, p<0.001).
CONCLUSIONS
Persistent MOG-IgG positivity and high remission titres are associated with an increased relapse risk. Longitudinal MOG-IgG titres could be useful to stratify patients to be treated with long term immunosuppression.

Identifiants

pubmed: 36460438
pii: jnnp-2022-330237
doi: 10.1136/jnnp-2022-330237
doi:

Substances chimiques

Myelin-Oligodendrocyte Glycoprotein 0
Autoantibodies 0
Immunoglobulin G 0

Types de publication

Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

201-210

Investigateurs

Francesca Rossi (F)
Zulliani Luigi (Z)
Edoardo Mampreso (E)
Silvia Gambara (S)
Sabrina Squilini (S)
Sara Matricardi (S)
Valentina Torri Clerici (VT)
Anna Nunzia Polito (AN)
Gabriella Di Rosa (GD)
Roberta Bedin (R)
Francesca Vitetta (F)
Antonio Varone (A)
Davide Maimone (D)
Alvino Bisecco (A)
Elena Di Sabatino (ED)
Sara Scannapieco (S)
Claudia Papi (C)
Simone Guerrieri (S)
Francesco Pisani (F)
Andrea Praticò (A)
Chiara Po (C)
Luisa Grazian (L)
Alice Passarini (A)
Stefania Bergamoni (S)
Sasha Rasia (S)
Roberto Bergamaschi (R)
Enrico Marchioni (E)

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: MG has received honoraria as a speaker and for the partecipation to Advisory boards from Roche, UCB and Alexion.

Auteurs

Matteo Gastaldi (M)

Neuroimmunology Research Unit, IRCCS Mondino Foundation, Pavia, Italy matteo.gastaldi@mondino.it.

Thomas Foiadelli (T)

Clinica Pediatrica, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy.

Giacomo Greco (G)

Department of Neurosciences, Università degli Studi di Pavia, Pavia, Italy.
Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy.

Silvia Scaranzin (S)

Neuroimmunology Research Unit, IRCCS Mondino Foundation, Pavia, Italy.

Eleonora Rigoni (E)

Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy.

Stefano Masciocchi (S)

Neuroimmunology Research Unit, IRCCS Mondino Foundation, Pavia, Italy.
Department of Neurosciences, Università degli Studi di Pavia, Pavia, Italy.

Sergio Ferrari (S)

Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.

Chiara Mancinelli (C)

MS Center, Spedali Civili of Brescia, Brescia, Italy.

Laura Brambilla (L)

Neuroimmunology and Neuromuscolar Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy.

Margherita Mancardi (M)

Child Neuropsychiatry Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Children's Sciences, Giannina Gaslini Institute, Genova, Italy.

Thea Giacomini (T)

Child Neuropsychiatry Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Children's Sciences, Giannina Gaslini Institute, Genova, Italy.

Diana Ferraro (D)

Department of Biomedical Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.

Marida Della Corte (M)

Department of Neurosciences, Division of Neurology, Santobono-Pausilipon Children's Hospital, Napoli, Italy.

Antonio Gallo (A)

Division of Neurology, Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Naples, Italy.

Massimiliano Di Filippo (M)

Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy.

Luana Benedetti (L)

Neurology Department, Ospedale Policlinico San Martino IRCCS, Genoa, Italy.

Giovanni Novi (G)

Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.

Maurizio Versino (M)

Department of Biotechnology and Life Sciences, University of insubria, Varese, Italy.

Paola Banfi (P)

Neurology and Stroke Unit, ASST SetteLaghi, Ospedale di Circolo/Fondazione Macchi, Varese, Italy.

Raffaele Iorio (R)

Department of Neuroscience, Institute of Neurology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Lucia Moiola (L)

Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Emanuela Turco (E)

Child Neuropsychiatry Unit, Mother and Child Department, University Hospital of Parma, Parma, Italy.

Stefano Sartori (S)

Pediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.

Margherita Nosadini (M)

Pediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.

Martino Ruggieri (M)

Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy.

Salvatore Savasta (S)

Clinica Pediatrica, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy.

Elena Colombo (E)

Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy.

Elena Ballante (E)

BioData Science Center, IRCCS Mondino Foundation, Pavia, Italy.
Department of Mathematics, University of Pavia, Pavia, Italy.

Sven Jarius (S)

Department of Neurology, University of Heidelberg, Heidelberg, Germany.

Sara Mariotto (S)

Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.

Diego Franciotta (D)

Neuroimmunology Research Unit, IRCCS Mondino Foundation, Pavia, Italy.

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