Article Text
Abstract
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.
- MULTIPLE SCLEROSIS
- MYELOPATHY
- MYELIN
Data availability statement
Data are available in a public, open access repository. Raw data are available at the Zenodo repository (DOI: 10.5281/zenodo.6631485)
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Data availability statement
Data are available in a public, open access repository. Raw data are available at the Zenodo repository (DOI: 10.5281/zenodo.6631485)
Footnotes
Collaborators Francesca Rossi (Neurology Unit, Mater Salutis Hospital, Legnago, Italy, francesca.rossi{at}aulsslegnago.it, patient recruitment and data collection), Zulliani Luigi (Multiple Sclerosis Centre, S. Bortolo Hospital, Vicenza, Italy, luigi.zuliani{at}aulss8.veneto.it, patient recruitment and data collection), Edoardo Mampreso (Headache Centre, Neurology - Euganea, Padua Health Unit, Padova, Italy, edoardo.mampreso{at}aulss6.veneto.it, patient recruitment and data collection), Silvia Gambara (Unit of Child Neurology and Psychiatry, ASST Spedali Civili, Brescia, Italy, silvia.gambara{at}asst-spedalicivili.it, patient recruitment and data collection), Sabrina Squilini (Department of Neuropsychiatry, Children Hospital "G. Salesi", Ospedali Riuniti, Ancona, Italy, sabrina.siliquini@ospedaliriunioni.marche.it, patient recruitment and data collection), Sara Matricardi (Department of Neuropsychiatry, Children Hospital "G. Salesi", Ospedali Riuniti, Ancona, Italy, sara.matricardi{at}yahoo.it, patient recruitment and data collection), Valentina Torri Clerici (Neuroimmunology and Neuromuscolar Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milano, Italy, Valentina.Torri{at}istituto-besta.it, patient recruitment and data collection), Anna Nunzia Polito (Department of Woman and Child, Neuropsychiatry for Child and Adolescent Unit, General Hospital "Riuniti" of Foggia, Foggia, Italy, annanupolito{at}gmail.com, patient recruitment and data collection), Gabriella Di Rosa (Unit of Child Neurology and Psychiatry, Department Human Pathology of the Adult and Developmental Age, Messina, Italy, gdirosa@unime.it, patient recruitment and data collection), Roberta Bedin (Department of Neurosciences, Ospedale Civile, Azienda Ospedaliero-Universitaria, Modena, Italy, bedin.roberta@aou.mo.it, patient recruitment and data collection), Francesca Vitetta (Ospedale Civile Azienda Ospedaliero-Universitaria di Modena, Modena, Italy, vitetta.francesca{at}aou.mo.it, patient recruitment and data collection), Antonio Varone (Department of Neurosciences, Division of Neurology, Santobono-Pausilipon Children's Hospital, Napoli, Italy, antoniovarone{at}live.com, patient recruitment and data collection), Davide Maimone (Multiple Sclerosis Center, Garibaldi Hospital, Catania, Italy, dmaimone{at}tiscali.it, patient recruitment and data collection), Alvino Bisecco (I Division of Neurology, Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, Italy, Alvino.bisecco{at}unicampania.it, patient recruitment and data collection), Elena Di Sabatino (Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy, elenadisab{at}gmail.com, Patient recruitment and data collection), Sara Scannapieco (Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy, sarascannapieco1{at}gmail.com, patient recruitment and data collection), Claudia Papi (Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy, claudia.papi13{at}gmail.com, patient recruitment and data collection), Simone Guerrieri (Neurology Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy, guerrieri.simone{at}hsr.it, patient recruitment and data collection), Francesco Pisani (Child Neuropsychiatry Unit, Neuroscience Division, Medicine & Surgery Department, University of Parma, Parma, Italy, francesco.pisani{at}unipr.it, patient recruitment and data collection), Andrea Praticò (Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy, andrea.pratico{at}unict.it, patient recruitment and data collection), Chiara Po' (Pediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, Treviso, Italy, chiarapo.ped{at}gmail.com, patient recruitment and data collection), Luisa Grazian (Pediatric Unit, ULSS 2 Marca Trevigiana, Ca' Foncello Hospital, Treviso, Italy, luisa.grazian{at}aulss2.veneto.it, patient recruitment and data collection), Alice Passarini (Child Neuropsychiatry Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy, alice.passarini{at}ospedaleniguarda.it, patient recruitment and data collection), Stefania Bergamoni (Child Neuropsychiatry Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy, STEFANIA.BERGAMONI{at}ospedaleniguarda.it, patient recruitment and data collection), Sasha Rasia (Multiple Sclerosis Center, Spedali Civili di Brescia, Presidio di Montichiari, Montichiari, Italy, Sasha.rasia{at}gmail.com), patient recruitment and data collection), Roberto Bergamaschi (IRCCS Mondino Foundation, Pavia, Italy, roberto.bergamaschi{at}mondino.it, patient recruitment and data collection), Enrico Marchioni (IRCCS Mondino Foundation, Pavia, Italy, enrico.marchioni{at}mondino.it, patient recruitment and data collection).
Contributors MG: original study design, data analysis and manuscript drafting. This authors is responsible for the overall content as guarantor. TF: patient recruitment and data collection and contribution to study design. GG and ER: patient recruitment and data collection, data analysis, figure drafting and manuscript revision. SSc: laboratory data. SM: manuscript revision. SF, SM, LB, MM,TG, DF, MDC, AG, MDF, LB, GN, MV, PB, RI, LM, ET, SSar, MN, MR, SSav, EC and SM: patient recruitment and data collection. EB and SJ: manuscript revision and data analysis. DF: original study design and manuscript revision.
Funding The present study was supported by the Italian Ministry of Health, 'Ricerca Corrente' Grant to the IRCCS Mondino Foundation (code RC22012B).
Competing interests MG has received honoraria as a speaker and for the partecipation to Advisory boards from Roche, UCB and Alexion.
Provenance and peer review Not commissioned; externally peer reviewed.
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