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between HLA-DRB1*15:01 and Epstein-Barr virus, Table 1: Revised diagnostic criteria for NMO
[3]
as well as the estrogen receptor, has also been very Definite NMO
[4]
well established. Optic neuritis
Acute myelitis
At least two of three supportive criteria
Neuromyelitis optica (NMO) is an autoimmune 1. Contiguous spinal cord MRI lesion extending over three
demyelinating disorder, predominantly characterized by vertebral segments
[5]
severe optic neuritis (ON) and transverse myelitis (TM). 2. Brain MRI not meeting diagnostic criteria for multiple sclerosis
3. NMO‑IgG seropositive status
It was considered as a variant of MS, but the discovery NMO: neuromyelitis optica; MRI: magnetic resonance imaging;
that most NMO patients have antibodies against IgG: immunoglobulin G
aquaporin-4 (AQP4) or NMO-immunoglobulin G (IgG),
dramatically changed our perception of the disease and NMO-IgG in the sera of Japanese patients with OSMS
[6]
brought NMO and its spectrum in the center of interest. and NMO, as well as the similar clinical and pathological
Researches trying to correlate NMO with specific HLA characteristics, indicate that both syndromes may
alleles took place in a limited extend in the last few belong to the same clinical entity. [16] NMO is more
years, especially in Japanese population, in which common in women than men (> 2/3). [17,18] More than
NMO appears its greatest frequency. Nevertheless, it 80% present the relapsing form of the disease, [17] while
has become clear that HLA play a crucial, and maybe the median age of onset is the late 30s, [18] with few
the primer role, in the genetic risk of NMO and provide reports of NMO occurrence in children [19] or elderly. [20]
great insight in the profound understanding of its Familial cases of NMO are estimated to account for 3%
pathogenesis and the differential diagnosis mainly from of all NMO cases. [21]
MS and other demyelinating diseases as well.
BASIC CLINICAL FEAUTURES AND
In this study, our aim was to summarize in a critical IMMUNOPATHOGENESIS
review the results of these researches worldwide and
shed light on the contribution of HLA alleles in NMO Neuromyelitis optica is characterized by ON, which
immunopathogenesis, given the total absence of such is often bilateral (simultaneously or sequentially),
a review. and longitudinally extensive TM with a well-defined
sensory level, as well as sphincter dysfunction, pain
HISTORICAL NOTES AND EPIDEMIOLOGY and tonic spasms of the trunk and extremities.
[8]
Involvement of the brain stem may cause hiccups,
Neuromyelitis optica was first described in 1870 by nausea and even respiratory failure, [22] while
Allbutt, who reported an association between myelitis hypothalamic-pituitary axis dysfunction commonly
and unilateral optic nerve disorder, but it was in 1894 manifests as hyponatremia, hyperthermia and
when the term “neuromyelite optique aigue” (acute hyperprolactinemia. [23] Encephalopathy mimicking
[7]
optic neuromyelitis) was coined by Devic in order posterior reversible encephalopathy syndrome has also
to describe patients who first suffered unilateral or been described. [24]
bilateral loss of vision and within weeks developed
severe spastic para- or tetraparesis, loss of sensation Clinical attacks generally progress over days, with
[8]
and sphincter control. In 1999, Wingerchuk et al. variable recovery within months. Most patients endure
proposed the first diagnostic criteria for NMO. Current some residual disability, which accumulates over
revised criteria for diagnosing NMO were defined in time. [8]
2006 by the same group [Table 1], because in 2004,
[9]
the AQP4 protein was identified for NMO, which Even though a review of the complicated mechanisms
was the first molecular target described for any type of pathogenesis of NMO is far from the purpose of our
of demyelinating diseases of the central nervous review, in order to explore in which ways HLA may
system (CNS). [6] contribute to it, we refer to some important aspects,
providing the basics for this purpose. AQP4-antibodies
Neuromyelitis optica represents < 1% of demyelinating have a decisive role in the pathogenesis of NMO, by
diseases of the CNS in Caucasians [10] and it is certainly complement-mediated astrocyte damage, cascading
more common in Asians. It has been reported to to leukocyte infiltration, oligodendrocyte death and
account for up to 30% of West Indian cases of CNS neuronal cell damage. [25] They are present in up to
demyelination, [11] 20-30% of Japanese cases, [12] 48% 80% of NMO cases. AQP4 is highly expressed in
of East Asian cases, [13] 23% of Indian cases [14] and astrocytic end-feet in the blood-brain barrier, nodes
15% of Afro-Brazilian cases. [15] Japanese patients with of Ranvier and neuronal synapses. [25] AQP4 is also
opticospinal MS (OSMS) or Asian MS represent a expressed in a sub-population of CNS ependymal
distinct entity from western MS. The equal detection of cells associated with the pia, subfornical organ and

Neuroimmunol Neuroinflammation | Volume 1 | Issue 2 | September 2014 45