OBJECTIVE: To determine the seroprevalence of neuromyelitis optica antibody (NMO)-IgG in Brazilian patients with clinical diagnosis of relapsing neuromyelitis optica, also known as Devic's disease. METHOD: We determined NMO-IgG titers in 28 patients (25 of them females) that fulfilled the 1999 NMO diagnostic criteria proposed by Wingerchuk et al. RESULTS: NMO-IgG was detected in 18 NMO patients (64.3%). CONCLUSION: Our results showed that seroprevalence of NMO-IgG in Brazilian NMO patients was similar to the observed in other studies.OBJETIVO: Determinar a soroprevalência do anticorpo neuromielite óptica (NMO)-IgG em pacientes brasileiros com diagnóstico de neuromielite óptica recorrente, também conhecida como doença de Devic. MÉTODO: Nós pesquisamos a presença do anticorpo NMO-IgG em 28 pacientes (25 do sexo feminino) que preenchiam os critérios diagnósticos para NMO propostos por Wingerchuk et al. em 1999. RESULTADOS: Dezoito pacientes (64,3%) apresentaram a pesquisa positiva do NMO-IgG. CONCLUSÃO: Nossos resultados demonstraram que a soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com NMO é semelhante àquela encontrada em outros estudos

ADONI, Tarso

CALLEGARO, Dagoberto

KOK, Fernando

LINO, Angelina Maria Martins

MARCHIORI, Paulo Eurípedes

Tarso Adoni

Angelina Maria Martins Lino

Paulo Eurípedes Marchiori

Fernando Kok

Dagoberto Callegaro

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Seroprevalence of NMO-IgG antibody in Brazilian patients with neuromyelitis optica Soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com neuromielite óptica

Universidade de São Paulo

Soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com neuromielite óptica

Biblioteca Digital da Produção Intelectual da Universidade de São Paulo (BDPI/USP)

Arq Neuropsiquiatr 2008;66(2-B):295-297
 295
SEROPREVALENCE OF NMO-IgG ANTIBODY IN 
BRAZILIAN PATIENTS WITH NEUROMYELITIS OPTICA 
Tarso Adoni1, Angelina Maria Martins Lino2, Paulo Eurípedes Marchiori3,  
Fernando Kok3, Dagoberto Callegaro4
Abstract – Objective: To determine the seroprevalence of neuromyelitis optica antibody (NMO)-IgG in Brazilian 
patients with clinical diagnosis of relapsing neuromyelitis optica, also known as Devic’s disease.  Method: We 
determined NMO-IgG titers in 28 patients (25 of them females) that fulfilled the 1999 NMO diagnostic criteria 
proposed by Wingerchuk et al.  Results: NMO-IgG was detected in 18 NMO patients (64.3%).  Conclusion: Our 
results showed that seroprevalence of NMO-IgG in Brazilian NMO patients was similar to the observed in 
other studies. 
KEY WORDS: neuromyelitis optica, Devic’s disease, NMO-IgG, seroprevalence.
Soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com neuromielite óptica
Resumo – Objetivo: Determinar a soroprevalência do anticorpo neuromielite óptica (NMO)-IgG em pacientes 
brasileiros com diagnóstico de neuromielite óptica recorrente, também conhecida como doença de 
Devic.  Método: Nós pesquisamos a presença do anticorpo NMO-IgG em 28 pacientes (25 do sexo feminino) 
que preenchiam os critérios diagnósticos para NMO propostos por Wingerchuk et al. em 1999.  Resultados: 
Dezoito pacientes (64,3%) apresentaram a pesquisa positiva do NMO-IgG.  Conclusão: Nossos resultados 
demonstraram que a soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com NMO é semelhante 
àquela encontrada em outros estudos.
PALAVRAS-CHAVE: neuromielite óptica, doença de Devic, NMO-IgG, soroprevalência.
Department of Neurology, University of São Paulo School of Medicine, São Paulo SP, Brazil: 1MD; 2MD, PhD; 3MD, PhD, Associate Professor; 4MD, PhD, 
Center for Myelin Disorders of Hospital das Clínicas, Chairman.
Received 13 December 2007, received in final form 8 April 2008. Accepted 24 April 2008.
Dr. Tarso Adoni – Rua Barata Ribeiro 414 /  41 - �13��-��� ��o Paulo �P - Brasil. E-�ail�� tarso�d��neuro.co�.br       
Neuromyelitis optica (NMO; Devic’s disease) and its 
spectrum disorders are idiopathic inflammatory demye-
linating diseases of the central nervous system (CNS) that 
mainly affect the optic nerves and spinal cord1. The hall-
mark of NMO pathology is the presence of necrotic spinal 
cord lesions involving both gray and white matter, often 
resulting in cavitation, as well as the presence of vascular 
hyalinization2. NMO and multiple sclerosis (MS) are cur-
rently considered different diseases since the description 
of NMO-IgG, a serum gamma immunoglobulin autoanti-
body that is a specific marker for NMO3,4. NMO-IgG selec-
tively binds to aquaporin-4 (AQP4) water channel, a com-
ponent of the dystroglycan protein complex of astrocyt-
ic foot processes at the blood-brain barrier5. Its sensitivity 
and specificity for NMO diagnosis were confirmed in sev-
eral studies and the presence of NMO-IgG is now one of 
the new diagnostic criteria for neuromyelitis optica4. 
NMO may represent the first example of a novel class 
of autoimmune channelopathy5. The clinical course of 
NMO is usually more severe than of MS. Within five years 
of onset, fifty percent of patients either lose functional 
vision in at least one eye or become unable to walk unas-
sisted6. Detection of the autoantibody enables early di-
agnosis of NMO, before the presence of a full-blown clin-
ical picture, allowing early initiation of appropriate immu-
nosuppressive therapy. 
This is the first study of frequency of NMO-IgG in a 
series of Brazilian relapsing NMO patients. 
METHOD
Twenty-eight patients with NMO from the Center for My-
elin Disorders of the Neurologic Clinic of São Paulo Universi-
ty School of Medicine, São Paulo, Brazil, were enrolled. All of 
them fulfilled the original criteria for diagnosis of NMO6. Demo-
graphic and clinical characteristics of patients included in our 
study are shown on Table 1. Briefly, median age at onset of dis-
ease was 27 years (range 7-51), median time of follow-up was 8 
years (range 1-14). The mean time elapsed between optic neuri-
tis and myelitis was 18 months (median 21; range 2-60), Kurtzke’s 
Expanded Disease Severity Score on last visit was 6.0 (range 2-8). 
Arq Neuropsiquiatr 2008;66(2-B)
296
Neuromyelitis optica
Adoni et al.
All patients presented with recurrent disease and were receiving 
azathioprine (3 mg/kg daily) when a blood sample was drawn for 
this study and sent to Mayo Clinic Rochester, Rochester, Min-
nesota, USA. Serum NMO-IgG was detected using the method-
ology described by Lennon et al.3 at Mayo Clinic. All subjects or 
their legal responsible signed the Informed Consent Form, and 
the study was approved by the Institutional Review Board and 
conducted in compliance with the Declaration of Helsinki. 
RESULTS
Serum NMO-IgG was detected in 18 (64.3%) of the 28 
patients enrolled. Female to male ratio was 8.3:1 and 75% 
of patients were non-whites.
DISCUSSION 
There are descriptions of the frequency of NMO-IgG 
in NMO patients in different populations7 (Table 2). The 
first publication included 102 North American patients 
with NMO or with high-risk syndromes for NMO (recur-
rent optic neuritis or longitudinally extensive transverse 
myelitis), and 12 Japanese patients with optic-spinal mul-
tiple sclerosis (OSMS). In that seminal paper the authors 
found sensitivity and specificity for NMO diagnosis of 73% 
and 91%, respectively3. In Japan, authors detected NMO-
IgG in more than half of OSMS patients (63% sensitivity)8, 
suggesting that NMO and OSMS could be the same entity. 
The prevalence of NMO and MS varies significantly 
among different regions of the world15,16. Such differences 
are due to variability in genetic susceptibility and environ-
mental factors17. MS in North American individuals of Euro-
pean extraction is associated with human leukocyte antigen 
(HLA) DRB1*1501 (DR2), while Asian individuals with HLA 
DPB1*0501 have a higher risk for NMO. Interestingly, HLA 
DPB1*0501 is present in 60% of the normal people in Japan, 
but in less than 10% of the North American population18-21.
In Brazil, HLA DQB1, DQA1 and DRB1 genotype vari-
ability according to ethnicity was analyzed22. The authors 
concluded that DQA1*0201-0301 alleles were associated 
with white Brazilian population and the DRB*1501 allele 
was present in European-Brazilians and DRB1*03-1503 in 
African-Brazilians; the DRB1*1501 allele confers an eth-
nicity-dependent MS susceptibility in European patients 
whereas DQB1*0602 allele confers genetic susceptibil-
ity regardless of ethnicity22. Maybe these findings could 
explain the higher prevalence of NMO in patients with 
African ancestry in virtue of ethnicity-dependent suscep-
tibility. In our sample of 28 patients with NMO, 18 were 
seropositive for the NMO-IgG antibody, 15 of them Afri-
can descents and only 3 European descents. 
To our knowledge this is the first report on the fre-
quency of NMO-IgG as a serological marker for NMO in 
Brazilian patients. In our series, among clinically defined 
NMO patients, NMO-IgG was positive in 64.3%. This sero-
prevalence is similar to that observed by others3,8. 
In a recent study23, multiple logistic analyses revealed 
that emergence of the anti-NMO-IgG antibody was 
Table 1. De�ographic and clinical characteristics o� patients with 
neuro�yelitis optica. 
Gender
  Male
  Female
3
25
Age at onset (years)
  Median
  Range
27
7-51
Ethnical origin
  African descents
  European descents
  Asian descents
20
7
1
Duration of follow-up ( years)
  Median
  Range
8
1-14
Time elapsed between optic 
neuritis and  myelitis (months)
  Median  
  Range  
21
2-60
EDSS on last clinical visit
  Median
  Range
6.0
2-8
Table 2. Frequency o� anti-aquaporin 4 antibody in di��erent populations.
Author Country NMO/OSMS (n) Positive %
Zuliani, 20069 Spain 10 50
Littleton, 200610 UK 10 50
Kim, 200611 Korea 27 19
Marignier, 200612 France 20 55
Jarius, 200713 Europe 35 54
Akman-Demir, 200614 Turkey 14 57
Present study Brazil 28 64.3
Arq Neuropsiquiatr 2008;66(2-B)
 297
Neuromyelitis optica
Adoni et al.
positively associated with a higher relapse rate. Thus, 
this method can be a useful and reliable tool in NMO 
diagnosis and management in Brazilian patients, in spite 
of ethnical differences and genetic peculiarities of our 
population. We hope that early detection of NMO-IgG in 
Brazilian patients with NMO and high-risk syndromes for 
NMO assures prompt and appropriate therapy. 
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Soroprevalência do anticorpo NMO-IgG em pacientes brasileiros com neuromielite óptica

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