Epstein-Barr virus (EBV) nuclear antigen (EBNA)-4 mutation in EBV-associated malignancies in three different populations

Different ethnic groups with a high human leukocyte antigen (HLA)-A11 prevalence have been shown to experience a high rate of Epstein-Barr virus (EBV) infection, EBV-associated malignancies, and Epstein-Barr nuclear antigen (EBNA)-4 mutations. The epitopes 393-408 and 416-424 of EBNA-4 are major antigenic epitopes that elicit an HLA-A11 cytotoxic T lymphocyte (CTL) response to EBV infection. Mutations selectively involving one or more nucleotide residues in these epitopes affect the antigenicity of EBNA-4, because the mutant EBV strains are not recognized by the HLA-A11-restricted CTLs. To investigate these mutations in common EBV-associated malignancies occurring in different populations, we studied the mutation rate of epitopes 393-408 and 416-424 of EBNA-4 in 25 cases of EBV-associated Hodgkin's disease (HD), nine cases of AIDS-related non-Hodgkin's lymphoma, and 37 cases of EBV-associated gastric carcinoma (GC) from the United States, Brazil, and Japan. We found one or more mutations in these two epitopes in 50% (6/12) of United States HD, 15% (2/13) of Brazilian HD, 50% (6/12) United States GC and 28% (7/25) Japanese GC, and 22% (2/9) of United States AIDS-lymphoma. Similar mutations were found in 30% (3/10) of United States reactive, 0% (0/6) of Brazilian reactive, and 25% (2/8) Japanese reactive tissues. The most frequent amino acid substitutions were virtually identical to those seen in previously reported isolates from EBV-associated nasopharyngeal carcinomas and Burkitt's lymphomas occurring in high prevalence HLA-A11 regions. However, only 2/28 (7%) mutations occurred in HLA-A11-positive patients. Our studies suggest that: 1) EBNA-4 mutations are a common phenomenon in EBV-associated HD, GC, and AIDS-lymphoma; 2) the mutation rate does not vary in these geographic areas and ethnic groups; 3) EBNA-4 mutations in EBV-associated United States and Brazilian HD, United States and Japanese GC, and United States AIDS lymphomas are not related to patients' HLA-A11 status.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Human leukocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection

HLA-G is a non-classic Human Leukocyte Antigen (HLA-G) Class I of low polymorphism and restricted tissue distribution that displays tolerogenic functions. In heart transplantation and in combined liver/renal allograft transplantation, the expression of HLA-G has been associated with a lower incidence of acute graft rejection episodes and absence of chronic dysfunction. Since the expression of HLA-G in renal biopsies has been investigated only in few patients who received a combined kidney and liver transplant, in this study we performed a cross-sectional study, systematically comparing the expression of HLA-G in post-transplanted renal grafts, stratifying patients according to the presence or absence of rejection.Patients and Methods: Seventy-three renal specimens (10 with acute rejection and 13 with chronic allograft nephropathy, and 50 with no signs of rejection) were immunohistochemically evaluated for HLA-G expression.Results: In the group as a whole, HLA-G molecules were detected in 40 cases (54.8%). Among specimens that presented HLA-G expression, 2 out of 40 (5%) exhibited acute rejection, 2 (5%) exhibited chronic allograft nephropathy, and the remaining 36 (90%) exhibited no signs of rejection. The comparison between patients with rejection and those without rejection showed that the expression of HLA-G was significantly increased in specimens exhibiting no signs of rejection (p<0.0001). Considering only patients with acute rejection, 8 out of 10 patients showed no HLA-G expression in their kidney biopsies when compared to patients exhibiting no signs of rejection and absence of HLA-G was observed in 14 out of 50 (p=0.0032). Similarly, considering only patients with chronic allograft nephropathy, absence of HLA-G expression was observed in I I out of 13 specimens, whereas in patients without rejection absence of HLA-G was observed in 14 out of 50 (p=0.003). Therapy with tacrolimus was significantly associated with the expression of HLA-G and a better graft prognosis. Conclusions: Our results suggest that HLA-G expression in the kidney allograft and the use of tacrolimus are associated with a lower frequency of acute renal rejection and chronic allograft nephropathy. (c) 2007 Elsevier B.V. All rights reserved.

Expression of human leucocyte antigen-G primarily targets affected skin of patients with psoriasis

P>BackgroundThe nonclassical human leucocyte antigen (HLA)-G molecule has been well recognized as a tolerogenic molecule and few studies have evaluated the role of the molecule in inflammatory cutaneous autoimmune diseases.ObjectivesTo evaluate the expression of HLA-G in skin specimens of patients with psoriasis and to analyse its correlation with epidemiological and clinical variables.MethodsThirty untreated patients with psoriasis and 32 healthy individuals were enrolled. Immunohistochemistry was applied to identify HLA-G expression in formalin-fixed paraffin-embedded cutaneous skin biopsies.ResultsSoluble and membrane-bound HLA-G expression was detected in 30 (90%) of the skin specimens from patients presenting clinical and histopathological features of psoriasis. Although infiltrating lymphomononuclear cells of the dermis exhibited HLA-G expression, the epidermis was primarily targeted. HLA-G expression was also observed in 27% (three of 11) of the specimens that exhibited no clinical and histopathological features of psoriasis (nonaffected areas). In contrast, skin specimens obtained from healthy individuals exhibited no HLA-G expression (P < 0 center dot 0001). The intensity of HLA-G expression was not associated with type I/II psoriasis, Psoriasis Area and Severity Index score or clinical forms.ConclusionsAs the HLA-G molecule was consistently expressed in affected and, to a lesser extent, in nonaffected areas of untreated patients with psoriasis, irrespective of the severity of the clinical variants, one may hypothesize that the presence of HLA-G may be responsible, at least in part, for the regulation of autoimmune effector cells.

Influence of HLA-DRB-1 alleles on the production of antibody against CSP, MSP-1, AMA-1, and DBP in Brazilian individuals naturally infected with Plasmodium vivax

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Both psoriasis and benign migratory glossitis are associated with HLA-Cw6

This study was undertaken to investigate human leucocyte antigen (HLA) associations with benign migratory glossitis and psoriasis in Brazilian patients and particularly to determine whether benign migratory glossitis is also associated with HLA-Cw6, the classical association observed in psoriasis. The results showed a highly significant association of Cw6 with both psoriasis and benign migratory glossitis, with this antigen being present in 59.% of the patients with psoriasis, in 43.8% of the patients with benign migratory glossitis, and in only 12.6% of the controls. Other significant positive associations, although at a lower significance level, were with B13, both in psoriasis and in benign migratory glossitis, and with B17, only in psoriasis. To our knowledge, this is the first report on the association of Cw6 with benign migratory glossitis. We believe that this finding reinforces the concept of a pathogenetic relationship between benign migratory glossitis and psoriasis.

Doença de Jorge Lobo e sua relação com os antígenos do sistema HLA

Pós-graduação em Doenças Tropicais - FMB

Polimorfismos do gene HLA-DRB1 associados à resposta imune humoral contra o antígeno-1 de membrana apical das variantes de Plasmodium vivax (VK210, VK247 e P. vivax-like)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genetic diversity among volunteer donors of bone marrow in southeastern Brazil, according to the HLA system

CONTEXTO E OBJETIVO:Para a realização de transplantes de medula óssea com material alogênico, é necessária a verificação de histocompatibilidade das moléculas do sistema HLA (human leukocyte antigen), fundamental para o sucesso desses transplantes. O objetivo desta pesquisa foi caracterizar os doadores de medula óssea segundo gênero, idade, etnia e grupos HLA de um centro regional de hemoterapia brasileiro.TIPO DE ESTUDO E LOCAL:Estudo descritivo dos doadores cadastrados em um centro regional de hemoterapia de um hospital público universitário da região Sudeste do Brasil.MÉTODOS:Foram consultadas as fichas dos 66.780 doadores cadastrados entre 2005 e junho de 2011 e tabuladas as variáveis estudadas.RESULTADOS:Encontrou-se distribuição equilibrada entre os gêneros, e 82,8% dos doadores tinham até 45 anos de idade. Quanto à etnia auto-referida, 77,3% se apresentaram como brancos, 15,0% como pardos, 5,7% como negros, os 2% restantes dividindo-se em outras etnias. Quanto à caracterização imunogenética, no grupo alélico HLA-A, o mais frequente foi o HLA-A*02, com 39,20%; no grupo alélico HLA-B, o mais comum foi o HLA-B*35, com 14,18%; no grupo alélico HLA-DRB1, o mais frequente foi o HLA-DRB1*03, com 17,03% do total de doadores. Quando esses resultados são comparados com os dados do cadastro nacional de doadores (REDOME), observam-se diferenças demográficas e imunogenéticas, que se explicam pelo histórico de imigração da região de Ribeirão Preto, no Sudeste brasileiro.CONCLUSÕES:Os resultados encontrados reforçam a importância de conhecer o perfil demográfico e imunogenético das regiões do Brasil, para reduzir o tempo de espera por um doador histocompatível.

Worldwide genetic variation at the 3 ' untranslated region of the HLA-G gene: balancing selection influencing genetic diversity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Worldwide HLA-E nucleotide and haplotype variability reveals a conserved gene for coding and 3 ' untranslated regions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Frequency of HLA-B27 alleles in Brazilian patients with psoriatic arthritis

This prospective study analyzed the frequency of HLA-B27 and its alleles in 102 Brazilian patients with psoriatic arthritis (PsA). The association of the HLA-B27 alleles with these variants was compared to a control healthy HLA-B27 positive group of 111 individuals. There was a predominance of male gender (59.8%), Caucasian race (89.2%), and negative HLA-B27 (79.4%) patients. Asymmetric oligoarthritis (62.7%) was the most frequently observed clinical PsA subgroup, followed by spondylitis (16.7%), and polyarthritis (15.7%). Male gender and the spondylitis subgroup were statistically associated to the positive HLA-B27, and the oligoarthritis subgroup was associated to the negative HLA-B27. Among the 21 HLA-B27-positive PsA patients, there was a significant prevalence of the HLA-B*2705 allele (90.5%), similar to that observed in the control group (80.2%); HLA-B*2703 and HLA-B*2707 were statistically associated to the control group.

Genotipagem de HLA de classe I e II para seleção de células precursoras dendríticas para estudo da imunobiologia do vírus associado ao Sarcoma de Kaposi (KSHV)

The Kaposi-associated Herpesvirus (KSHV) also known as Human Herpesvirus 8 (HHV-8) is associated with the development of Kaposi’s sarcoma (KS) and others limphoprolipheratives diseases such as Primary Effusion Lymphoma (PEL) and Multicentric Castleman Disease (MCD). Even though the virus is considered lymphotropic, it is able to infect others cell types such as macrophages, dendritic cells, endothelial cells, monocytes and fibroblasts. After infection, KSHV be latent expressing essential viral genes to its maintenance in a infected cell. However, in some circumstances may occur the reactivation of lytic cycle producing new viral particles. K1 protein of KSHV interferes in the cellular signaling inducing proliferation and supporting cellular transformation. K1 is encoded by viral ORF-K1, which shows high variability between different genotypes of KSHV. So far, it is not clear whether different isoforms of K1 have specific immunobiological features. The KSHV latency is maintained under strict control by the immune system supported by an adequate antigen presentation involving Human Leucocyte Antigen (HLA) class I and II. Polymorphisms of HLA class I and II genes confer an enormous variability in molecules that recognize a large amount of antigens, but also can increase the susceptibility to autoimmune diseases. Therefore, the present study aims to genotype HLA class I (A and B) and class II (DR and DQ) from volunteers to identify haplotypes that can provide better response to K1 epitopes of different KSHV genotypes. First of all, 20 volunteers were selected to genotype HLA genes. In our results we observed prevalence of certain HLA class I haplotypes as HLAA1, HLA-A2, HLA-A24, HLA-A26, HLA-B8, HLA-B18 e HLA-B44. After the in silico analysis using BIMAS and SYFPEITHI databases, we observed high scores for epitopes from the B genotype of KSHV, indicating...(Complete abstract click electronic access below)

The frequency of HLA-DRB1 polymorphisms in Brazilian Plasmodium vivax malaria patients and in blood donors from the Amazon Region

We evaluated the frequency of different HLA-DRB1 alleles in Plasmodium vivax-infected individuals and in healthy blood donors from malaria endemic areas of Brazil. Low-resolution human leukocyte antigen-DRB1 genotyping was performed for 73 malaria patients and 29 healthy blood donors. The most frequent alleles in individuals from northern Brazil were human leukocyte antigen-DRB1*04, *08, *07 and *13. The frequency of human leukocyte antigen-DRB1*07 was higher in malaria-infected individuals than in the control group, which reinforces the theory that this allele plays an important role in susceptibility to malaria. This study offers new information about a potential susceptibility factor for P. vivax malaria in a Brazilian population that is naturally exposed to malaria.

Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)