Linking discrete event simulation models using HLA

The increasing usage of discrete event simulation packages for modeling and analyzing manufacturing and logistics has led to a need for connecting simulation models together at runtime. One such methodology for linking discrete event simulation models together has been developed for this research and this paper demonstrates the usage of this linking method. A unified simulation model is developed from two submodels developed using different simulation packages.

Frequency of human leukocyte antigen (hla) in patients with malaria and in the general population of Humaitá county, Amazonas state, Brazil

Em agosto de 1983 foram observados 85 habitantes do Município de Humaitá, Estado do Amazonas, Brasil, com a finalidade de estudar a prevalência dos antígenos de HLA -A, -B, -C e DR, dentre os quais 38 eram doentes com malária causada pelo Plasmodium falciparum Todos eles foram examinados para avaliação de esplenomegalia, exame parasitológico de sangue e pesquisa de anticorpos de malária. Foram constituídos três grupos: (I) 25 indivíduos nascidos na região Amazônica que nunca tiveram malária; (II) 38 indivíduos naturais da Amazônia que tinham sido tratados de malária no passado, ou que estavam tendo malária atual, e (III) 22 doentes com malária que contraíram na Amazônia e eram procedentes de outras regiões do Brasil. Foram colhidas amostras de sangue de cada um deles, separados os linfôcitos e os antígenos de HLA foram tipados pelo teste de microlinfocitotoxidade. Houve elevada freqüência de antígenos não identificados, nos grupos estudados, o que sugere ou a existência de homozigoze, oufenôtipo não identificado nessa população. Houve alta freqüência fenotípica de antígeno deAg(W24) (44,7%) no Grupo II, quando comparado ao Grupo 1(32%) ou Grupo III (9%). Os indivíduos do Grupo II mostraram também elevada freqüência do antígeno DR4 (80%) quando comparado ao Grupo 1(36,3%) ou Grupo III(16,6%). Essas observações sugerem a possibilidade de suscetibilidadegenética ã malária entre os nativos da Amazônia e indicam a necessidade da realização de inquéritos mais extensos sobre a freqüência de antígenos de HLA em habitantes de zona endêmica de malária.

Influence of HLA alleles in response to treatment with pegylated interferon-alpha and ribavirin in patients with chronic hepatitis C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Proteção de bovinos contra Haemonchus placei e Haemonchus contortus após imunização com antígenos oriundos da membrana intestinal de H. contortus

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

Avaliação da resposta de anticorpos contra antígenos de Plasmodium vivax relacionada a fatores genéticos do parasito e do hospedeiro humano

Pós-graduação em Genética - IBILCE

Busca de antígenos para diagnóstico da leishmaniose visceral canina: potencial uso e aplicação da proteína rLc36

Pós-graduação em Biotecnologia - IQ

Análise da expressão de antígenos câncer/testítulo (CTs) em pacientes com mieloma múltiplo

O mieloma múltiplo (MM) é uma neoplasia maligna secundária à expansão clonal de células plasmáticas caracterizada pela presença de imunoglobulina monoclonal no sangue e/ou na urina, lesões líticas ósseas e infiltração de plasmócitos monoclonais na medula óssea. A caracterização dos mecanismos responsáveis pela expansão das células tumorais do MM é difícil e envolve uma série de alterações genéticas e mudanças no microambiente da medula óssea, favorecendo o crescimento do tumor e a falha do sistema imune em reconhecê-lo. O MM é uma doença incurável, sendo a sobrevida mediana dos pacientes em torno de 3-5 anos. Terapias atuais como quimioterapia e transplante autólogo de células-tronco podem induzir remissão da doença, mas a recaída e a morte são inevitáveis. Os antígenos específicos câncer/testículo (CTs) foram originalmente descritos em pacientes com melanoma e são assim denominados, pois suas proteínas foram identificadas em espermatogônias, células conhecidas por não expressarem antígenos de histocompatibilidade (HLA), o que as impossibilita de desencadear uma resposta imune específica. Esses antígenos foram identificados posteriormente em vários tipos de tumores humanos, como melanoma, carcinoma pulmonar, câncer renal, entre outros. Até o momento, existem poucas informações a respeito de sua importância como fatores de prognóstico clínico ou relacionado à proliferação aberrante das células plasmáticas. Assim, o objetivo deste estudo é avaliar o nível de expressão gênica dos antígenos câncer/testículo MAGEC1(CT7), MAGEA3/6, LAGE-1, NY-ESO-1 e GAGE em amostras de aspirado de medula óssea total de pacientes com mieloma múltiplo. A análise de expressão por RT-PCR dos 5 CTs de interesse, realizada em 21 amostras de medula total de pacientes com MM, demonstrou as seguintes freqüências: CT7 (42,9%), LAGE-1 (23,8%)... (Resumo completo, clicar acesso eletrônico abaixo)

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)

Obtenção de anticorpos monoclonais murinos contra antígenos de Staphylococcus aureus resistentes à meticilina por imunização subtrativa

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Susceptibility to toxoplasmic retinochoroiditis is associated with HLA alleles reported to be implicated with rapid progression to AIDS

Background/aims: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC). Methods: 98 AIDS patients (25 with TRC, 43 with anti-T. gondii antibodies but without TCR, and 30 without anti-T. gondii antibodies and without TCR) were studied. Results: The HLA-B35 was significantly increased in TRC group (p = 0.0038). Conclusion: The presence of HLA-B35 may simultaneously predispose to progression to AIDS and TRC.

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives. IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM. Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes. The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.

Crystal structure of the HLA-Cw3 allotype-specific killer cell inhibitory receptor KIR2DL2

Killer cell inhibitory receptors (KIR) protect class I HLAs expressing target cells from natural killer (NK) cell-mediated lysis. To understand the molecular basis of this receptor-ligand recognition, we have crystallized the extracellular ligand-binding domains of KIR2DL2, a member of the Ig superfamily receptors that recognize HLA-Cw1, 3, 7, and 8 allotypes. The structure was determined in two different crystal forms, an orthorhombic P212121 and a trigonal P3221 space group, to resolutions of 3.0 and 2.9 Å, respectively. The overall fold of this structure, like KIR2DL1, exhibits K-type Ig topology with cis-proline residues in both domains that define β-strand switching, which sets KIR apart from the C2-type hematopoietic growth hormone receptor fold. The hinge angle of KIR2DL2 is approximately 80°, 14° larger than that observed in KIR2DL1 despite the existence of conserved hydrophobic residues near the hinge region. There is also a 5° difference in the observed hinge angles in two crystal forms of 2DL2, suggesting that the interdomain hinge angle is not fixed. The putative ligand-binding site is formed by residues from several variable loops with charge distribution apparently complementary to that of HLA-C. The packing of the receptors in the orthorhombic crystal form offers an intriguing model for receptor aggregation on the cell surface.

Definition of HLA-DQ as a transplantation antigen

Recent studies have demonstrated the importance of recipient HLA-DRB1 allele disparity in the development of acute graft-versus-host disease (GVHD) after unrelated donor marrow transplantation. The role of HLA-DQB1 allele disparity in this clinical setting is unknown. To elucidate the biological importance of HLA-DQB1, we conducted a retrospective analysis of 449 HLA-A, -B, and -DR serologically matched unrelated donor transplants. Molecular typing of HLA-DRB1 and HLA-DQB1 alleles revealed 335 DRB1 and DQB1 matched pairs; 41 DRB1 matched and DQB1 mismatched pairs; 48 DRB1 mismatched and DQB1 matched pairs; and 25 DRB1 and DQB1 mismatched pairs. The conditional probabilities of grades III-IV acute GVHD were 0.42, 0.61, 0.55, and 0.71, respectively. The relative risk of acute GVHD associated with a single locus HLA-DQB1 mismatch was 1.8 (1.1, 2.7; P = 0.01), and the risk associated with any HLA-DQB1 and/or HLA-DRB1 mismatch was 1.6 (1.2, 2.2; P = 0.003). These results provide evidence that HLA-DQ is a transplant antigen and suggest that evaluation of both HLA-DQB1 and HLA-DRB1 is necessary in selecting potential donors.

IMGT/HLA Database—a sequence database for the human major histocompatibility complex

The IMGT/HLA Database (www.ebi.ac.uk/imgt/hla/) specialises in sequences of polymorphic genes of the HLA system, the human major histocompatibility complex (MHC). The HLA complex is located within the 6p21.3 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and these include the 21 highly polymorphic HLA genes, which influence the outcome of clinical transplantation and confer susceptibility to a wide range of non-infectious diseases. The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools and detailed descriptions of the source cells. The online IMGT/HLA submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. The latest version (release 1.7.0 July 2000) contains 1220 HLA alleles derived from over 2700 component sequences from the EMBL/GenBank/DDBJ databases. The HLA database provides a model which will be extended to provide specialist databases for polymorphic MHC genes of other species.