Abstract
BackgroundMyelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative.AimsTo identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing versus non-relapsing subgroups of MOGAD.MethodsThree groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4+ T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (Tregs, Foxp3+), CD45RA-Foxp3+ Tregs and subpopulation naive Tregs (CD45RA+Foxp3int), effector Tregs (CD45RA-Foxp3high) and non-suppressive Tregs (CD45RA-Foxp3int) proportions were determined.ResultsThe mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4+ Tregs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA-Foxp3+ Tregs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector Tregs/non suppressive-Tregs, which was significantly higher than in MOGNR.ConclusionsOur findings suggest that CD4+ Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of Tregs to rh-MOG in MOGNR, where CD4+ Tregs increased, and in MOGR, where CD45RA-Foxp3+ Tregs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease.
Highlights
Pediatric acquired demyelinating syndromes (ADS) are rare immune-mediated acute demyelinating disorders of the central nervous system (CNS) with an incidence of 0.6 to 1.6 for 100,000 children per year in western countries [1,2,3]
The gender proportion of each group was similar as analyzed by Chi-square test, but relapsing MOGAD (MOGR) occurred only in female in our cohort (5/5, 100%), a proportion significantly higher than that in MOGAD can be either non-relapsing (MOGNR) (Fisher’s exact test p = 0.027) and in multiple sclerosis (MS) (Fisher’s exact test p = 0.044)
An increase of Th2 and Th17 after stimulation by rhMOG was observed in ADS children with MOG antibody-associated disease (MOGAD), in MOGNR
Summary
Pediatric acquired demyelinating syndromes (ADS) are rare immune-mediated acute demyelinating disorders of the central nervous system (CNS) with an incidence of 0.6 to 1.6 for 100,000 children per year in western countries [1,2,3]. Myelin oligodendrocytes glycoprotein (MOG) antibodies (Abs) are found in about 25% of pediatric ADS [4] referred to as MOG antibody-associated disease (MOGAD). MS is an ADS characterized by the recurrence of demyelination episodes resulting in subsequent neurological damage. Both MOGAD and MS have T and B lymphocytes infiltration in the brain, but in MS, CD8+ T cell and B cell infiltration is higher [11] than in MOGAD where CD4+ T cell infiltration is predominant [12]. Myelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
