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Original research
Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort
  1. Xiaobo Sun1,
  2. Wei Qiu1,
  3. Jingqi Wang1,
  4. Shisi Wang1,
  5. Yuge Wang1,
  6. Xiaonan Zhong1,
  7. Chunxin Liu1,
  8. Chunping Cui1,
  9. Hai Hong2,3,
  10. Hui Yang4,
  11. Xiao-Jing Li5,
  12. Zhengqi Lu1,
  13. Xueqiang Hu1,
  14. Allan G Kermode6,7,
  15. Lisheng Peng1
  1. 1Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  2. 2Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Guangzhou, China
  3. 3The Institute of Immunology of Zhong Shan Medical School, Sun Yan-sen University of Medical Sciences, Guangzhou, China
  4. 4Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  5. 5Guangzhou Women and Children's Medical Center Guangzhou Children's Hospital, Guangzhou, China
  6. 6Neurology, Western Australian Neuroscience Research Institute, Nedlands, Western Australia, Australia
  7. 7Murdoch University, Institute for Immunology and Infectious Diseases, Murdoch, Western Australia, Australia
  1. Correspondence to Professor Lisheng Peng, Department of Neurology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; penglsh5{at}mail.sysu.edu.cn

Abstract

Objective Myelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus.

Methods HLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG).

Results Paediatric-onset MOGAD 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 MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, 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 undergo a disease relapse (p=0.030). HLA–peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen–antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele.

Conclusions This study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD.

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Footnotes

  • XS and WQ contributed equally.

  • Contributors WQ, LP and AGK contributed to study concept and design. All authors contributed to data acquisition and analysis. XS, SW and JW drafted the manuscript. XS and WQ contributed equally as first authors to the manuscript.

  • Funding This work was supported by grants from the National Natural Science Foundation of China (grant number 81 971 140 and 81870953) and the Natural Science Foundation of Guangdong Province, China (grant number 2017A030313853 and 2014A030312001).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the ethics committees of each participating institution (Ethics Number: Third Affiliated Hospital of Sun Yat-sen University [2014] 2–15).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Corresponding author: Professor Lisheng Peng, email: penglsh5@mail.sysu.edu.cn.

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