Protective Effect of HLA-DRB1*11 and Predisposition of HLA-C*04 in the Development of Severe Liver Damage in Brazilian Patients with Chronic Hepatitis C Virus Infection

The objective of this study was to investigate human leucocyte antigen (HLA) genes in patients chronically infected with hepatitis C virus (HCV) and to analyse the possible role of these genes in the progression of chronic hepatitis C. One hundred and forty-five (145) Brazilian patients infected only with HCV genotype 1 were evaluated. HLA class I (A*, B*, C*) and class II (DRB1*, DQA1*, DQB1*) typing were carried out by PCR-SSO, through Luminex technology. Associations were found with protection against development of liver damage by both DRB1*11 (5.0% versus 18.2%, P = 0.0016, OR = 0.23, CI 95% = 0.090.58; Pc=0.0208) and DRB1*11-DQA1*05-DQB1*03 haplotype (4.2% versus 15.3%, P = 0.0032; OR = 0.24, CI 95% = 0.08-0.64). Liver damage was associated with HLA-C*04 in patients with <20 years of infection (38.4% versus 9.1%, P = 0.002, OR = 6.25, CI 95% = 1.9719.7; Pc=0.0238). It is concluded that HLA alleles can influence the development of liver damage in HCV type-1 chronically infected Brazilian patients.

Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

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.

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)

HLA-E coding and 3' untranslated region variability determined by next-generation sequencing in two West-African population samples

HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5'UTR, introns and the 3'UTR) in two African population samples, Susu from Guinea-Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3'UTR is quite polymorphic and (d) haplotypes in the HLA-E 3'UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes.

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)

Peripheral giant cell granuloma. An immunohistochemical and ultrastructural study.

OBJECTIVE: To study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections of 40 cases of PGCG were immunohistochemically stained for vimentin, alpha I-antichymotrypsin, CD68, S-100 protein, lysozyme, leucocyte common antigen (LCA), factor VIII-related antigen and muscle cell actin. Six cases of PGCG were also studied by transmission electron microscopy. RESULTS: Vimentin, alpha I-antichymotrypsin and CD68 were expressed in both the mononuclear and multinucleated giant cells. Dendritic mononuclear cells, positive for S-100 protein, were noted in 67.5% of the lesions, whereas lysozyme and leucocyte common antigen were detected in occasional mononuclear cells. Ultrastructural examination showed mononuclear cells with signs of phagocytosis and sometimes interdigitations with similar cells. Others presented non-specific characteristics and the third type exhibited cytoplasmic processes and occasional Birbeck granules. Some multinucleated giant cells showed oval nuclei, abundant mitochondria and granular endoplasmic reticulum whereas others presented with irregular nuclei and a great number of cytoplasmic vacuoles. CONCLUSIONS: Immunohistochemical and ultrastructural results suggest that PGCGs of the jaws are composed mainly of cells of the mononuclear phagocyte system and that Langerhans cells are present in two thirds of the lesions.

Influence of Fc gamma RIIIb polymorphism on its ability to cooperate with Fc gamma RIIa and CR3 in mediating the oxidative burst of human neutrophils

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

The immunomodulatory effect of propolis on receptors expression, cytokine production and fungicidal activity of human monocytes

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

The modulatory effects of caffeic acid on human monocytes and its involvement in propolis action

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

Typing class I HLA-A gene using a nested PCR-RFLP procedure

In order to detect several new HLA-A class I alleles that have been described since 1998, the original PCR-RFLP method developed to identify the 78 alleles recognized at that time at high resolution level was adapted by us for low and medium resolution levels using a nested PCR-RFLP approach. The results obtained from blood samples of 23 subjects using both the PCR-RFLP method and a commercial kit (MicroSSP1A®, One Lambda Inc.) showed an agreement higher than 95%. The PCR-RFLP adapted method was effective in low and medium resolution histocompatibility evaluations.

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)

Coinfecção pelos vírus da hepatite C (VHC) vírus da imunodificência humana (HIV): polimosrfismo dos sistemas HPA -1, -3, 3 e -5

Pós-graduação em Fisiopatologia em Clínica Médica - 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)