RESUMO
BACKGROUND: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system. OBJECTIVES: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness. METHODS: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures. RESULTS: In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) in secondary infections (odds ratio [OR] = 0.46, 95% confidence interval [CI], .30-.72), while the HLA-A02 supertype (OR = 1.92, 95% CI, 1.30-2.83) and the HLA-A01/03 supertype (OR = 3.01, 95% CI, 1.01-8.92) were associated with susceptibility to secondary dengue fever. The B07 supertype was associated with susceptibility to secondary DHF in the univariate analysis (OR = 1.60, 95% CI, 1.05-2.46), whereas that was not retained in the final model. CONCLUSIONS: As the HLA-B44 supertype is predicted to target conserved epitopes in dengue, our results suggest that B44 supertype-restricted immune responses to highly conserved regions of the dengue proteome may protect against secondary DHF.
Assuntos
Vírus da Dengue , Etnicidade , Genes MHC Classe I/fisiologia , Dengue Grave/virologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Análise Multivariada , Razão de Chances , Dengue Grave/etnologia , Dengue Grave/imunologia , Tailândia/epidemiologiaRESUMO
Natural killer (NK) cells are key components of the innate immune system that have been implicated in the immune response against tumor cells. Killer cell immunoglobulin-like receptors (KIR) regulate NK cell activity by interaction with specific human leukocyte antigen (HLA) class I. In this study, KIR gene polymorphisms and their HLA ligands were investigated in Thai patients with chronic myelogenous leukemia (CML) (n=60), acute myelogenous leukemia (AML) (n=60), acute lymphoblastic leukemia (ALL) (n=55), and diffuse large B-cell lymphoma (DLBCL) (n=60) compared with 150 healthy controls. The frequency of KIR3DL1 with HLA-Bw4 was significantly lower in DLBCL patients than in controls (P=0.0006, Pc=0.02), whereas no significant differences were seen in KIR gene frequencies and their ligands between leukemia patients and controls. This study suggest a role of inhibitory KIR with its ligand in the protection against DLBCL.
Assuntos
Antígenos HLA-B/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Linfoma Difuso de Grandes Células B/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores KIR3DL1/genética , Adolescente , Adulto , Idoso , Alelos , Povo Asiático , Estudos de Casos e Controles , Criança , Feminino , Expressão Gênica , Frequência do Gene , Antígenos HLA-B/imunologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/etnologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Aguda/etnologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Ligantes , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptores KIR3DL1/imunologia , TailândiaRESUMO
Genetic factors of the host have been shown to influence the outcome of treatment for hepatitis C virus (HCV) infection. Killer cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell activity by interaction with specific human leukocyte antigen (HLA) class I. In this study, KIR gene polymorphisms and their HLA ligands were investigated in 110 Thai patients with chronic HCV genotype 3a. Seventy-six patients were sustained virological responders and 34 patients were virological non-responders. KIR typing and HLA-C typing were performed using PCR-SSP (polymerase chain reaction with sequence specific primer). The frequency of HLA-C1C2 was significantly higher in sustained responders than in non-responders (P = 0.04). However, the frequencies of KIR2DL2/2DL3 genotype and KIR2DL2/2DL3-HLA-C1C1 genotype were significantly higher in non-responders than in sustained responders (P = 0.02, 0.004, respectively). In summary, this study showed the association of KIR genes and ligands with the outcome of antiviral treatment in chronic hepatic C virus genotype 3a infection.
