Immunogenetics of MHC and KIR in the Leprosy

Several genetic polymorphisms in immune response genes have been associated to leprosy. This fact converges on the main hypothesis that genetic factors are involved in the disease susceptibility in two distinct steps: leprosy per se and their clinical forms. These genes play an important role in the recognition process, in the activation of the main metabolic pathway of the immune response and in the evolution of the disease. The scope of this project was to highlight the role of the immune response genes in the context of leprosy, emphasizing the participation of some of them in the signaling and targeting processes in response to bacillus infection and on disease evolution, such as HLA, KIR and MIC genes. Some environmental and genetic factors are important when the exposure to the bacillus occurs, leading to cure or not. Factors that favor a cellular or humoral immune response may influence the clinical manifestations after the infection inducting to one of extreme poles. Furthermore, some genetic factors were associated to the type of reaction that some individuals present during the disease development. Thus, it is very important to highlight the participation of some genetic factors in the immunopathogenesis of leprosy

Immunopathogenesis of Chronic Periodontitis

Periodontitis is a chronic inflammatory condition characterized by destruction of non-mineralized and mineralized connective tissues. The pathogenesis of periodontitis involves a complex interplay between periodontopathogens and the host immunity, greatly influenced by genetic and environmental factors. Failure in the inflammation resolving mechanism leads to establishment of a chronic inflammatory process, resulting in the progressive destruction of bone and soft tissue. The aim of this chapter is to summarize the role of innate and specific immune response involved in pathogenesis of periodontitis. Cells and inflammatory mediators, those participating in inflammatory process of the ligamentous supporting structure and in resorption of alveolar bone, will be presented

Development and implantation of PCR-SSP for the genotyping of JAK2 V617F mutation / Desenvolvimento e implantação de metodologia molecular baseada em PCR-SSP para genotipagem da mutação V617F de JAK2

The JAK2 protein promotes cells growth and proliferation, and mutations in the JAK2 gene can result in increase of the number of blood cells and in development of myeloproliferative neoplasms. This study aimed to develop and implement the PCR-SSP (Sequence-Specific Primer - Polymerase Chain Reaction) to detect the JAK2V617F mutation. Therefore, a literature review about genotyping methodologies for this mutation was conducted and primers were based on the model proposed by Xavier (2009), tested and adjusted to the best amplification condition. The PCR-SSP technique was standardized and was effective for the detection of the JAK2V617F mutation. As it is not expensive, the technique reduces costs and can be implanted even in small molecular biology laboratories, helping the diagnosis of patients with myeloproliferative diseases and favoring research related to this gene

Associação de HLA-DR2 com cardiopatia crônica em uma população da região noroeste do Estado do Paraná, Brasil

A doença de Chagas é um dos maiores problemas que afetam a saúde pública no Brasil e outros países latino americanos. No entanto, poucos trabalhos avaliaram a susceptibilidade genética a esta doença. Como genes de resposta imune estão localizados no Complexo de Histocompatibilidade HLA, decidimos estudar a associação entre os antígenos HLA e a forma cardíaca da doença de Chagas, que parece apresentar um componente auto-imune importante. Trinta e cinco pacientes e 72 controles residentes na região noroeste do estado do Paraná foram utilizados neste estudo. Métodos estatísticos clássicos foram usados para comparar as freqüências HLA entre pacientes e controles. Os dados confirmam uma associação primária com HLA-DR2 (48.4%vs12.3%; Pc=0,0011) e secundária com HLA-B7 (31.4%vs8.3%; Pc=0.033). Concluindo, uma associação positiva entre DR2 e cardiopatia chagásica crônica foi demonstrada numa população de brancos brasileiros, reforçando a hipótese do envolvimento de fatores genéticos na susceptibilidade à forma cardíaca da doença de Chaga

Association Between Human Leukocyte Antigens And Graft-versus-host Disease Occurrence After Allogenic Hematopoietic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.130219-2

Genetic polymorphisms of Rh, Kell, Duffy and Kidd systems in a population from the State of Paraná, southern Brazil

BACKGROUND: Red blood group genes are highly polymorphic and the distribution of alleles varies among different populations and ethnic groups. AIM: To evaluate allele polymorphisms of the Rh, Kell, Duffy and Kidd blood group systems in a population of the State of Paraná METHODS: Rh, Kell, Duffy and Kidd blood group polymorphisms were evaluated in 400 unrelated blood or bone marrow donors from the northwestern region of Paraná State between September 2008 and October 2009. The following techniques were used: multiplex-polymerase chain reaction genotyping for the identification of the RHD gene and RHCE*C/c genotype; allele-specific polymerase chain reaction for the RHDΨ and restriction fragment length polymorphism polymerase chain reaction for the RHCE*E/e, KEL, FY-GATA and JK alleles. RESULTS: These techniques enabled the evaluation of the frequencies of Rh, Kell, Duffy and Kidd polymorphisms in the population studied, which were compared to frequencies in two populations from the eastern region of São Paulo State. CONCLUSION: The RHCE*c/c, FY*A/FY*B, GATA-33 T/T, JK*B/JK*B genotypes were more prevalent in the population from Paraná, while RHCE*C/c, FY*B/FY*B, GATA-33 C/C, JK*A/JK*B genotypes were more common in the populations from São Paulo.212

Padronização da extração de DNA genômico a partir de diferentes fases do leite humano/ Standardization of genomic DNA extraction from different phases of human milk

O leite humano (LH) é um fluido fisiológico composto por eletrólitos, glicídios, glicoproteínas e células nucleadas, como leucócitos e células epiteliais mamárias. Posto isso, o LH pode ser uma fonte viável e segura para a obtenção de DNA comparado à extração pelo sangue periférico, visto que não é necessário realizar o acesso venoso periférico nas puérperas, o que seria incômodo para elas. Dessa forma, devido à escassez de informações na literatura, este trabalho propõe a padronização de técnicas para extração de DNA do LH em suas diferentes fases (colostro, transição e maduro) pelas seguintes metodologias: Salting out, Qiagen QIAamp DNA Mini Kit™ e Biopur®. Os resultados das três técnicas de extração produziram um DNA de maior pureza, porém em concentrações mais baixas, ainda que suficientes para processos de amplificação, comparado ao DNA extraído pelo sangue periférico

Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.12613