Ethnicity-dependent association of HLA DRB1-DQA1-DQB1 alleles in Brazilian multiple sclerosis patients

-Neuromyelitis optica (NMO; Devic's disease) and its spectrum disorders are idiopathic inflammatory demyelinating diseases of the central nervous system (CNS) that mainly affect the optic nerves and spinal cord 1 . The hallmark 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 hyalinization 2 . NMO and multiple sclerosis (MS) are currently considered different diseases since the description of NMO-IgG, a serum gamma immunoglobulin autoantibody that is a specific marker for NMO 3,4 . NMO-IgG selectively binds to aquaporin-4 (AQP4) water channel, a component of the dystroglycan protein complex of astrocytic foot processes at the blood-brain barrier 5 . Its sensitivity and specificity for NMO diagnosis were confirmed in several studies and the presence of NMO-IgG is now one of the new diagnostic criteria for neuromyelitis optica 4 .NMO may represent the first example of a novel class of autoimmune channelopathy 5 . 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 unassisted 6 . Detection of the autoantibody enables early diagnosis of NMO, before the presence of a full-blown clinical picture, allowing early initiation of appropriate immunosuppressive therapy. This is the first study of frequency of NMO-IgG in a series of Brazilian relapsing NMO patients. METHODTwenty-eight patients with NMO from the Center for Myelin Disorders of the Neurologic Clinic of São Paulo University School of Medicine, São Paulo, Brazil, were enrolled. All of them fulfilled the original criteria for diagnosis of NMO 6 . Demographic and clinical characteristics of patients included in our study are shown on Table 1. Briefly, median age at onset of disease was 27 years (range 7-51), median time of follow-up was 8 years (range 1-14). The mean time elapsed between optic neuritis 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).

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Seroprevalence of NMO-IgG antibody in Brazilian patients with neuromyelitis optica

Adoni

Lino

Marchiori

et al. 2008

“…We found significantly association of HLA DQB1*0602, HLA DRB1*1501 and DRB1*1503 alleles with ADEM monophasic patients. The HLA DQB1*0602 allele confers genetic susceptibility to Brazilian MS patients from Rio de Janeiro City (RJC), independently of the genetic background [21][22][23] . The presence of a common allele conferring genetic susceptibility for both MS and ADEM in the same population was found by Idrissovaet al 20 among Russian MS and ADEM patients.…”

Section: Discussionmentioning

confidence: 99%

“…A linkage genetic study in children showed that ADEM was associated with HLA DRB1*01 and DRB1*017(03) in the Russian population, and these alleles are associated with MS in Russian patients 20 . In Brazil, MS has been associated with HLA DR2 in Caucasian 21 patients and with HLA DQB1*0602 independently of DRB1*1501, in African-descendent patients of Rio de Janeiro City (RJC) [21][22][23] .…”

mentioning

confidence: 99%

Acute disseminated encephalomyelitis: clinical features, HLA DRB11501, HLA DRB11503, HLA DQA10102, HLA DQB10602, and HLA DPA1*0301 allelic association study

Alves-Leon

Veluttini-Pimentel

Gouveia

et al. 2009

-We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4%) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3% were male and follow-up range was 8.5 to 16 years. Two cases (13.3%) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3%) presented MRI with multiple large lesions. CSF was normal in 73.3%. The severe disability observed at EDSS onset improved in 86.66% patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.KEy WoRDS: ADEM, HLA class II, demyelinating disease.Encefalomielite aguda disseminada: características clínicas e estudo de associação com os alelos HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602 e DPA1*0301Resumo -Avaliamos as frequencia, características demográficas, clínicas e de associação genética dos alelos HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 e DPA1*0301 em pacientes com diagnóstico de encefalomielite aguda disseminada (ADEM) em população com doença desmielinizante do SNC. Quinze (8,4%) pacientes de nossa série foram diagnosticados como ADEM. A média de idade foi 35,23 anos (variando entre 12 e 77), 53,3% eram homens e o tempo de acompanhamento variou entre 8,5 e 16 anos. Dois casos (13,3%) apresentaram infecção prévia, um apresentou processo desmielinizante para infeccioso e outro havia se submetido a vacinação para hepatite B quatro semanas antes. o EDSS variou entre 3,0 e 9,5. oito pacientes (53,3%) apresentaram grandes lesões na RM. o LCR foi normal em 73,3%. A incapacidade grave quantificada pelo EDSS foi seguida de melhora importante em 86,6% dos pacientes. A susceptibilidade genética na ADEM foi significativamente associada com os alelos HLA DQB1*0602, DRB1*1501 e DRB1*1503 (p<0,05) nos pacientes com quadro monofásico. PALAVRAS-CHAVE: ADEM, HLA classe II, doenças desmielinizantes.

“…This can be seen from a study by Alves-Leon et al 1 , in which they demonstrated the existence of heterogeneous phenotypes of HLA-DRB1*1501 in a population of healthy Brazilians that included both African descendants and white subjects. It is known that these alleles can negatively influence the therapeutic response to interferon.…”

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confidence: 93%

Epidemiological profile in multiple sclerosis patients, Uberaba, MG, Brazil

Grzesiuk¹

2011

about the epidemiological characteristics of patients with multiple sclerosis (MS) in the city of Uberaba-MG, Brazil. In this article, the authors comment on the similarity of most of the clinical and epidemiological features found in Uberaba to those presented in other samples in Brazil. However, when considering ethnicity, which in their study was predominantly Caucasian (85.71%), they cite the example of the city of Recife, where the incidence was predominantly in the black population (93.3%). They also mention the difficulties of ethnic classification in the Brazilian population, given the racial characteristics observed in our population.We agree that these difficulties exist but, nonetheless, we believe that ethnic traits need to be better studied in Brazil, with regard to the therapeutic options for multiple sclerosis. This can be seen from a study by Alves-Leon et al. 1 , in which they demonstrated the existence of heterogeneous phenotypes of HLA-DRB1*1501 in a population of healthy Brazilians that included both African descendants and white subjects. It is known that these alleles can negatively influence the therapeutic response to interferon. In another study, Brum et al. 2 drew attention to the fact that HLA-DRB1 may exhibit behavior of either resistance or susceptibility in response to ethnic background and environmental factors.Brazil is a country of continental dimensions with a high degree of miscegenation. However, this miscegenation is variable with regard to demographic distribution. Ethnic characteristics need to be reviewed more carefully because surveys on the epidemiology of MS in some Brazilian cities have found that the rate of cases of MS among the black population was greater than that observed in other studies, especially in the cities of Rio de Janeiro (28%) 3 and Cuiabá (26%) 4,5 . This implies that there is a need for regional and multicenter studies on MS in Brazil, especially in relation to the genetic susceptibility and environmental variables observed in a country with the dimensions of Brazil.Our congratulations to the authors. Perfil clínico e evolutivo no município do Rio de Janeiro. Rev Bras Neurol 1995;31:75-87. 4. Grzesiuk AK. Características clínicas e epidemiológicas de 20 portadores de esclerose múltipla acompanhados em Cuiabá-Mato Grosso. Arq