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

Abstract

BackgroundIgG 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.MethodsIn 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%)).ResultsWe 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).ConclusionsPersistent 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.

Serum MOG IgG titres should be performed routinely in the diagnosis and follow-up of MOGAD: Yes

“…Several studies found that persistent MOG-IgG seropositivity is associated with an increased likelihood of having a relapse by a factor of 2-10 7-10 particularly when the MOG-IgG titre remains high. 7,9,10 In a recent study of 116 children with MOGAD, MOG-IgG titres decreased significantly overtime in patients with a monophasic disease course compared to patients with a relapsing disease course in the majority of children. 9 This decline of MOG-IgG titres was most prominent during the first 12 months after disease onset and a seroconversion defined as a MOG-IgG titre of less than…”

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease

“…High titers are needed for MOGAD diagnosis, and seronegative conversion is associated with decreased relapse risk (9). Furthermore, relapsing MOGAD patients have higher MOG-IgG titer at remission compared to monophasic MOGAD (139). Treatments such as IVIG, Plasmapheresis, or FcRn blockers target pathogenic antibodies in the blood, including MOG-IgG.…”

Reply to “MOG‐IgG‐Associated Bilateral Optic Neuritis in Temporal Relation to Monkeypox Vaccination”

“…3 Second, recent findings indicate a mismatch between neuroanatomical-functional mapping at the level of meta and group analyses relative to analyses conducted in individual participants. For example, Van Essen and Glasser 4 showed that a group "striplike" definition of the FFA does not align with the definition of face-selective regions on the FG in individual hemispheresa mismatch reflective of a conversation in the broader human brain mapping field between a balance of large N studies and "precision imaging" studies in individual participants. 5,6 As such, the present study by Cohen et al motivates future research with (at least) two options: there is a relationship between tuber involvement of the FFA in ASD diagnosis in individual participants, or instead, there is a relationship between a focal neuroanatomical location of the posterolateral temporal lobe and ASD diagnosis outside of face-selective regions.…”

“…Even with the appropriate assay, interpretation of MOG IgG is dependent on timing of assay relative to associated neurologic symptoms. MOG IgG can be transiently positive during active MOG antibody‐associated disease when monophasic, and persistently positive MOG IgG can provide prognostic guidance on the likelihood of relapsing disease 4 …”

“…MOG IgG can be transiently positive during active MOG antibody-associated disease when monophasic, and persistently positive MOG IgG can provide prognostic guidance on the likelihood of relapsing disease. 4 The two patients in our case series who had imaging and cerebrospinal fluid findings most concerning for MOG antibody-associated disease did receive MOG IgG testing during the acute phase of illness. Patient 1 was tested on hospital day two and again at postdischarge follow-up with negative cell-based assay with quantification by flow cytometry (Mayo Clinic Laboratories) both times.…”