Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (p = 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (p = 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe auto-immune disease of the central nervous system driven by pathogenic antibodies mainly directed against aquaporin-4 (AQP4-Ab). Treatment of NMOSD currently relies on immunosuppressants (mycophenolate mofetil, azathioprine) or B-cell-depleting therapy (rituximab). B-cell differentiation into antibody-producing cells requires T follicular helper cells (Tfh). There are several Tfh subsets that differentially affect B-cell differentiation; Tfh2 and Tfh17 subsets strongly support B-cell differentiation. By contrast, Tfh1 lack this capacity and T follicular regulatory cells (Tfr), inhibit B-cell differentiation into antibody-producing cells. We performed a broad characterization of circulating Tfh subsets in 25 NMOSD patients and analyzed the impact of different treatments on these subsets. Untreated NMOSD patients presented a Tfh polarization toward excessive B-helper Tfh subsets with an increase of Tfh17 and (Tfh2+Tfh17)/Tfh1 ratio and a decrease of Tfr and Tfh1. Rituximab restored the Tfh polarization to that of healthy controls. There was a trend toward a similar result for azathioprine and mycophenolate mofetil. Our results suggest that NMOSD patients present an impaired balance in Tfh subsets favoring B-cell differentiation which may explain the sustained antibody production. These findings provide new insights into the pathophysiology of NMOSD, and further suggest that Tfh and Tfr subsets could be considered as potential therapeutic target in NMOSD because of their upstream role in antibody production.