Abstract
BackgroundHLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population.Methodology/Principal FindingsThe allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection.Conclusions/SignificanceThese data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections.
Highlights
Dengue viral infections have become one of the most important mosquito borne viral infections in the world and is one of the major emerging infectious diseases
In this study we have identified HLA class I and class II alleles that are associated with the development of dengue haemorrhagic fever (DHF) during primary dengue (PD) infection and secondary dengue (SD) infection and alleles that are strongly associated with the development of dengue shock syndrome (DSS)
Given that 72% of children aged 12 years from the Colombo district in Sri Lanka are seropositive to dengue [22] it is likely that the majority of individuals who consisted of our normal population would have had at least one dengue virus infection
Summary
Dengue viral infections have become one of the most important mosquito borne viral infections in the world and is one of the major emerging infectious diseases. It is estimated that 2.1 million cases of dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) occur every year resulting in 21,000 deaths [1]. Cross reactive memory T cells and cross reactive antibodies have been suggested to contribute to immunopathology by altering the cytokine profiles during secondary infection and are believed to be less effective in eliminating the newly infective virus serotype [4,5]. They are thought to lead to enhanced viral replication and severe clinical disease. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population
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