The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females.

The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females / O polimorfismo rs4774*C no gene CIITA em conjunção com o alelo HLA-DRB1*15:01 é um possível fator de susceptibilidade a esclerose múltipla em mulheres brasileiras

The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

O objetivo deste estudo foi investigar a associação entre alelos HLA, loci DQA1, DQB1 e DRB1, polimorfismos -168A/G e +1614G/C no gene CIITA, e suscetibilidade à esclerose múltipla (EM) em uma amostra de Rio de Janeiro, Brasil. Além disso, buscou-se determinar se alguma dessas associações pode ser gênero-dependente. Foram analisadas amostras de DNA de 52 pacientes com EM reincidente-remitente (EMRR) e 126 controles saudáveis ​​pareados por sexo e idade. Foi identificada associação significativa HLA-DRB1*15:01-EMRR, que foi específica para o gênero feminino (Odds Ratio (OR) = 4,78, p = 0,001). Além disso, observou-se que o polimorfismo +1614 G/C, em combinação com o alelo HLA-DRB1*15:01 provoca o aumento da susceptibilidade à EM em pacientes do sexo feminino (OR = 4,55, p = 0,01). Juntos, estes resultados destacam a natureza poligênica da EM.

Brain MRI abnormalities in Brazilian patients with neuromyelitis optica.

Brain abnormalities in neuromyelitis optica (NMO) have been reported previously, but the pathophysiological mechanism and clinical relevance of these abnormalities are poorly understood. We assessed the prevalence and patterns of brain MRI abnormalities in a Brazilian cohort of patients with NMO. Conventional brain MRI and medical records from 24 Brazilian patients with NMO were retrospectively evaluated. Brain MRI were classified into four subgroups: normal, non-specific lesions, multiple sclerosis (MS)-like lesions, and typical lesions. Brain lesions were detected in 19 patients (79.2%). Fourteen patients (58.3%) had non-specific lesions, three (12.5%) had MS-like lesions, and two (8.3%) had typical lesions. Differences between these subgroups with respect to the Expanded Disability Status Scale (EDSS) scores (p=0.86) were not significant. This study demonstrates a high prevalence of brain abnormalities in Brazilian patients with NMO; however, we did not find a significant relationship between these abnormalities and EDSS scores.

The role of demyelination in neuromyelitis optica damage: diffusion-tensor MR imaging study.

PURPOSE: To test the hypothesis that white matter damage in neuromyelitis optica (NMO) is more extensive than previously described and likely includes involvement of normal-appearing white matter and to explore by using diffusion-tensor (DT) imaging whether white matter lesions are not only related to wallerian degeneration but are also caused by demyelination. MATERIALS AND METHODS: Seventeen patients with NMO (mean age, 45 years; 14 women) were compared with 17 sex- and age-matched control subjects. The institutional review board approved the study, and all subjects gave written informed consent. In addition to conventional magnetic resonance imaging sequences, DT imaging was performed along 30 noncollinear directions by using a 1.5-T imager. For tract-based spatial statistics (TBSS) analysis, the white matter skeleton was created, and a permutation-based inference with 5000 permutations with a threshold of P less than .05 to enable the identification of abnormalities in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) was used. Partial correlation was applied to identify whether the number of clinical relapses and disease duration were correlated with all TBSS parameters. RESULTS: TBSS showed multiple areas with significant FA decrease in patients with NMO, mainly located in the corona radiata, uncinate fasciculus, corpus callosum, optic radiation, internal and external capsules, and cerebral peduncles. The mean FA, RD, and AD in the abnormal voxels located on the corpus callosum were, respectively, 0.69 ± 0.03 (standard deviation), 0.39 × 10(23) mm(2)/sec ± 0.04, and 1.53 × 10(23) mm(2)/sec ± 0.04 in patients with NMO compared with 0.75 ± 0.02, 0.33 × 10(23) mm(2)/sec ± 0.03, and 1.57 × 10(23) mm(2)/sec ± 0.04 in control subjects (P < .0001, P < .0001, and P = .007, respectively). There was a highly significant inverse correlation between FA and RD (r = 20.976, P < .0001). CONCLUSION: The use of TBSS allowed the identification of extensive white matter damage in patients with NMO. Multiple white matter tracts were involved, including the pyramidal tract, optic radiation, and corpus callosum, likely related to both demyelination and wallerian degeneration.