RESUMO
BACKGROUND: Ability to predict the manner in which a recipient's immune system would respond to a transplanted graft by analyzing cytokine profiles of the "allograft antigen sensitized" recipient lymphocytes in vitro might provide a means to identify patients at risk to adverse clinical endpoints. METHODS: Cytokine/chemokine gene expression profiles of peripheral blood mononuclear cells co-cultured with allograft antigen-pulsed macrophages were studied in 49 renal transplant recipients-12 with acute cellular rejection (ACR) with or without antibody-mediated rejection (AMR), 7 with AMR (without ACR), and 30 with stable allografts (SA). An 86-gene inflammatory cytokines and receptors PCR array was used to measure fold changes in gene expression between pulsed and un-pulsed cultures. RESULTS: On linear discriminant analysis and multivariate analysis of variance, a gene set comprising C3, CCL3, IL1B, TOLLIP, IL10, CXCL5, ABCF1, CCR3, IL10RB, CXCL1, and IL1R1 differentiated the ACR-AMR from the SA group. Similarly, a gene set comprising IL10, C3, IL37, IL1B, CCL3, CARD18, and TOLLIP differentiated the AMR from the SA group. No significant difference was found between the ACR-AMR vs AMR groups. CONCLUSION: Distinct post in vitro stimulation cytokine profiles at the time of transplantation thus correlated with the occurrence of post-transplantation rejection episodes which indicated feasibility of this in vitro model to assess the recipient's anti-graft response at an early stage.
Assuntos
Citocinas/genética , Citocinas/imunologia , Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Teste de Histocompatibilidade/métodos , Isoantígenos/imunologia , Transplante de Rim/efeitos adversos , Linfócitos/imunologia , Adulto , Aloenxertos , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Análise Discriminante , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Humanos , Imunidade Celular , Imunidade Humoral , Modelos Lineares , Macrófagos/imunologia , Masculino , Análise Multivariada , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Transcriptoma , Resultado do TratamentoRESUMO
BACKGROUND: Genetic variation in HLA genes influence the immune response and may thus contribute to differential development of tuberculosis (TB) in HIV-infected individuals. The study was designed to determine whether HLA polymorphisms influence the development of Mycobacterium tuberculosis infection in HIV-infected individuals. MATERIALS AND METHODS: Fifty HIV-positive individuals without TB (HIV+TB-), 50 HIV patients co-infected with TB (HIV+TB+) and 50 control subjects (HIV-TB-) were analyzed for HLA Class I and II polymorphisms. RESULTS: In HLA Class II, frequency of occurrence of DRB1*13 (OR 3.165, CI 1.176-8.518, P value 0.019), DRB5 (OR 2.253, CI 1.011-5.019, P value 0.045) and DQB1*06 (OR 2.705, CI 1.197-6.113, P value 0.016) were increased in HIV+TB+compared to HIV+TB-. HLA DQB1*02 (OR 0.436, CI 0.185-1.029, P value 0.05) on the other hand conferred a protective role. In HLA Class I, frequency of B*15 (OR 2.705, CI 1.040-7.036, P value 0.038) was increased, whereas B*51 (OR 0.148, CI 0.031-0.706, P value 0.007) was decreased in HIV+TB+group compared to HIV+TB-. These differences however were not significant when compared with healthy controls. CONCLUSION: HLA polymorphisms independently did not account for the susceptibility to either of the disease mostly, although they seem to play a role once the infection(s) has established in a particular individual. Further studies are needed on a larger sample size to confirm these observations.