MOG antibody disease: the determinants of clinical phenotype and disease activity

Abstract

The significance of antibodies to myelin oligodendrocyte glycoproteins (antiMOGIgG1) in demyelinating disorders of the central nervous system was initially drawn around neuromyelitis optica spectrum disorders (NMOSDs), particularly in those patients that did not express antibodies to aquaporin four (AQP4IgG). As further research studies and clinical observations have emerged, it now seems likely myelin oligodendrocyte glycoproteins (MOG)related disease is a separate entity, with wider and more variable clinical and radiological presentations. This tenet applies whether considering NMOSD, isolated or recurrent optic neuritis, long or short transverse myelitis, brainstem or Acute dissaminated encephalomyelitis (ADEM)like presentations, encephalitis or rarely isolated cranial nerve involvement. To reinforce such an hypothesis, recent reports have been published to establish that the histopathological changes in MOG antibody associated disease(MOGAD) are different from those observed in AQP4IgGpositive NMOSD and multiple sclerosis. Ongoing research in the field is rapidly evolving. However, as these are essentially rare disorders, international and multicentre collaborative work will be essential to draw meaningful conclusions. In this vein, the paper by Liu and colleagues presents interesting insights when comparing the clinical characteristics of G (MOGAD) across Japanese and German cohorts. Worldwide, there remains insufficient information about the prevalence of MOGAD outside of the umbrella of NMOSD. Interestingly, an epidemiological study conducted by the Oxford group found that MOGAD was more prevalent than AQP4IgGpositive NMOSD. We certainly need to have more information about characteristics of MOGAD in different parts of the world. In the study by Liu and colleagues, the authors found that by comparing cohorts of patients from Germany and Japan, cerebral syndromes were more common (27% vs 4%) and myelitis less common (21% vs 50%) in Japanese patients with MOGAD. This variability of clinical presentation across different ethnicities may reflect the significance of genetic and environmental factors in the disease presentation. Separately, Liu and colleagues also reported that the disease severity and number of relapses were more prominent in the Japanese cohort when compared with German patients. This finding may add to previous arguments about the influence of ethnicity, but we need to bear in mind that the treatment approach was different between the two groups in this observational study. This may not be surprising, given that a recent survey among experts in the field showed variation in management approach to patients with MOGAD, in different centres and in different regions. As such, it seems timely to consider larger scale collaborations, and the establishment of a worldwide registry, to prospectively study patients with MOGAD, their clinical presentations, immunological and biochemical characteristics and genetic underpinnings. Moreover, as a community, we should start steering the wheel towards clinical trials for targeted treatment in this immunologically homogeneous group, where patient numbers are ever expanding.