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Review Article

Human leukocyte antigens‑immunogenetics of

neuromyelitis optica or Devic’s disease and the

impact on the immunopathogenesis, diagnosis

and treatment: a critical review

Maria Panos Gontika , Maria Constantinos Anagnostouli 1,2
1
1 Department of Neurology, Medical School of National and Kapodistrian University of Athens, Aeginition Hospital, Athens 11528, Greece.
2 Department of Neurology, Immunogenetics Laboratory and Division of Demyelinating Diseases, Medical School of National and
Kapodistrian University of Athens, Aeginition Hospital, Athens 11528, Greece.

ABSTRA CT

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.
Key words: Diagnosis, human leukocyte antigens‑immunogenetics, immunopathogenesis, neuromyelitis optica, treatment

INTRODUCTION recent researches which used current molecular
methods (sequence specific oligonucleotide-polymerase
Since its very first discovery and disease association chain reaction [PCR], single specific primer-PCR and
studies in early 1970’s, the major histocompability single-nucleotide polymorphisms, genome-wide
complex (MHC) with its polymorphisms has been association study, etc.) and which were conducted
[1]
the “gold standard” and the primer genetic locus in in many MS cohorts, made clear that HLA-DRB1*15:01
attributing genetic burden for certain autoimmune is by far the main independent, responsible allele for
diseases, like multiple sclerosis (MS). Initial studies, attributing genetic risk in different MS ethnic groups.
[1]
using serological techniques, showed an association In addition, co-existence of certain alleles probably
of MS with human leukocyte antigens (HLA) leads to an increase or decrease of the overall risk,
[1]
class I, especially HLA-A3 and HLA-B7. Multiple
via epistatic mechanisms (i.e. HLA-DRB1*15:01 and
[1]
Access this article online HLA-DQ1*01:02). Moreover, a Vitamin D response
Quick Response Code: element has been found in the promoter region of
Website: HLA-DRB1*15:01, changing the expression of the allele
www.nnjournal.net
and the risk for the disease. Thus, an environmental factor,
the sunlight, via the metabolites of Vitamin D, has been
DOI:
10.4103/2347-8659.139713 linked to the genome, especially to HLA-DRB1*15:01
and finally to the disease phenotype. The interaction
[2]

Corresponding Author: Prof. Maria Constantinos Anagnostouli, Department of Neurology, Immunogenetics Laboratory and
Division of Demyelinating Diseases, Medical School of National and Kapodistrian University of Athens, Aeginition Hospital,
Vassilisis Sofias Avenue 72‑4, Athens 11528, Greece. E‑mail: managnost@med.uoa.gr

44 Neuroimmunol Neuroinflammation | Volume 1 | Issue 2 | September 2014