Human leukocyte antigens-immunogenetics of neuromyelitis optica or Devic's disease and the impact on the immunopathogenesis, diagnosis and treatment: a critical review

Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder, predominantly characterized by severe optic neuritis, transverse myelitis and the high level of antibodies against aquaporin-4 (AQP4) or NMO-immunoglobulin G (IgG). Researches trying to correlate NMO with specific human leukocyte antigen (HLA) alleles took place in a limited extend in the last few years. Nevertheless, it has become clear that HLAs play a crucial role in the genetic risk of NMO, in the understanding of its pathogenesis and the differential diagnosis mainly from multiple sclerosis (MS), and also from other demyelinating diseases. In this study, we retrieved all the available data in the MEDLINE concerning the distribution of HLA frequencies in NMO and NMO-spectrum diseases, in all available ethnic groups, and compared them with those of MS. The results suggest that, the well-established HLA-DRB1*15:01 allele, associated with MS, plays rather a protective role for NMO. HLA-DRB1*03 allele is highly frequent in the NMO-IgG positive Caucasian patients, while HLA-DPB1*05:01 is the predominant allele in Japanese patients. The HLA-genotype and anti-AQP4 presence are the common immunological components in cases of comorbidity of NMO and other autoimmune diseases. The authors aim to summarize in the critical review the results of these researches worldwide, create a workable table including all this information for an easier reading approach and highlight the importance of these results in therapeutic decision making, using the HLA profile as biomarker in patients' stratification