Abstract
Background: Myelin oligodendrocyte glycoprotein-encephalomyelitis (MOG-EM) is a rare new neurological autoimmune disease with unclear pathogenesis. The linkage of the disease to the human leukocyte antigen (HLA) has not been shown.
Objective: To investigate the possible association between MOG-EM and HLAsubtypes.
Methods: HLA genotypes of 95 consecutive patients with MOG-EM, assessed between 2016 and 2018 form three academic centres, were compared to those of 481 healthy Chinese Han individuals. Patients with MOG-EM included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for immunoglobulin-G targeting the myelin oligodendrocyte glycoprotein.
Results: Paediatric-onset MOG-EM was associated with the DQB1*05:02-DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOG-EM was significantly higher than among healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOG-EM was not associated with any HLA genotype. Furthermore, patients with the DQB1*05:02-DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to have disease relapse (p=0.030). Analysis using HLA-peptide binding prediction algorithms and computational docking supported the idea of a close relationship between the MOG peptide subunit and DQB1*05:02 haplotype. The results of in vitro experiments indicated that site-specific mutations of the predicted target sequence reduced antigen-antibody binding, especially in the paediatric-onset group with DQB1*05:02 haplotype.
Conclusions: The present study demonstrated a possible association between specific HLA class II alleles and paediatric-onset MOG-EM, supporting the conclusion that different mechanisms likely underlie paediatric- and adult-onset cases of MOG-EM.