HLA association in MOG-IgG- and AQP4-IgG-related disorders of the CNS in the Dutch population

Neurol Neuroimmunol Neuroinflamm. 2020 Mar 20;7(3):e702. doi: 10.1212/NXI.0000000000000702. Print 2020 May.


Objective: To investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.

Methods: Blood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG-seropositive and 42 AQP4-IgG-seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.

Results: No significant HLA association was found in MOG-IgG-seropositive patients. The AQP4-IgG-seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707-5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513-8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495-5.042, pc = 0.0199) compared with controls.

Conclusions: The present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG-positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG-positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aquaporin 4 / immunology*
  • Child
  • Child, Preschool
  • Demyelinating Autoimmune Diseases, CNS / blood
  • Demyelinating Autoimmune Diseases, CNS / genetics*
  • Demyelinating Autoimmune Diseases, CNS / immunology*
  • Female
  • HLA Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Netherlands
  • Neuromyelitis Optica / blood
  • Neuromyelitis Optica / genetics
  • Neuromyelitis Optica / immunology
  • White People
  • Young Adult


  • AQP4 protein, human
  • Aquaporin 4
  • HLA Antigens
  • MOG protein, human
  • Myelin-Oligodendrocyte Glycoprotein