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Myelin oligodendrocyte glycoprotein encephalomyelitis is associated with HLA subtypes in a Chinese paediatric-onset cohort

Sun, X., Wang, S., Wang, J., Wang, Y., Zhong, X., Liu, C., Cui, C., Hong, H., Yang, H., Li, X., Lu, Z., Hu, X., Kermode, A.G., Peng, L. and Qiu, W. (2020) Myelin oligodendrocyte glycoprotein encephalomyelitis is associated with HLA subtypes in a Chinese paediatric-onset cohort. Multiple Sclerosis Journal, 26 (9). NP87.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Sage Publications
Other Information: Poster session 12 given @ PACTRIMS 2019
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