%0 Journal Article
%T HLA-B*44 Is Associated with Dengue Severity Caused by DENV-3 in a Brazilian Population
%A Liciana Xavier Eurico de Alencar
%A Ulisses de Mendonˋa Braga-Neto
%A Eduardo Jos谷 Moura do Nascimento
%A Marli Ten車rio Cordeiro
%A Ana Maria Silva
%A Carlos Alexandre Antunes de Brito
%A Maria da Paz Carvalho da Silva
%A Laura Helena Vega Gonzales Gil
%A Silvia Maria Lucena Montenegro
%A Ernesto Torres de Azevedo Marques J迆nior
%J Journal of Tropical Medicine
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/648475
%X Human leukocyte antigen (HLA) alleles have been correlated with susceptibility or resistance to severe dengue; however, few immunogenetic studies have been performed in Latin American (LA) populations. We have conducted immunogenetic studies of HLA class I and II alleles in a cohort of 187 patients with DENV-3 infection and confirmed clinical diagnosis of either severe dengue, known as dengue hemorrhagic fever (DHF), or the less severe form, dengue fever (DF), in Recife, Pernambuco, Brazil. An association analysis was performed using Fisher＊s association test, with odds ratios (ORs) calculated using conditional maximum likelihood estimates. HLA-B*44 ( , OR = 2.025, 95% CI = 0.97每4.24) was found to be associated with increased susceptibility to DHF in response to DENV-3 infection. In addition, HLA-B*07 ( , OR = 0.501, one-sided 95% CI = 0每0.99) and HLA-DR*13 ( , OR = 0.511, one-sided 95% CI = 0每0.91) were found to be associated with resistance to secondary dengue infection by DENV-3. These results suggest that HLA-B*44 supertype alleles and their respective T-cell responses might be involved in susceptibility to severe dengue infections, whereas the HLA-B*07 supertype alleles and DR*13 might be involved in cross-dengue serotype immunity. 1. Introduction Dengue virus (DENV) has four serotypes, named as DENV-1, DENV-2, DENV-3 and DENV-4. The majority of dengue infections are subclinical; however, the clinical manifestations of dengue infection range from the benign, self-limited dengue fever (DF) to a vasculopathy syndrome known as dengue hemorrhagic fever (DHF) that can lead to hypovolemic dengue shock syndrome (DSS). It is often observed in epidemiological studies that the more severe illness occurs more frequently in secondary heterotypic dengue infection [1每7]. There are two main hypotheses to explain the higher frequency of DHF in secondary infections. The first is that heterotypic antibodies would bind to the dengue virus and would facilitate the viral entry into cells expressing Fc receptors; this theory is known as antibody dependent enhancement (ADE) [8, 9]. The second hypothesis is that anti-dengue memory T cells that cross-react with related but altered peptide epitopes would induce the T cells to produce abnormal levels of cytokines leading to vasculopathy. This theory is known as ※original antigenic sin§ (OAS) or ※altered peptide ligand§ (APL). The theories are not mutually exclusive, and both are based on the fact that previous dengue infection is a risk factor for developing more severe disease. However, 99% or more of the secondary dengue
%U http://www.hindawi.com/journals/jtm/2013/648475/