title: HLA class I and class II associations in dengue viral infections in a Sri Lankan population.
abstract: BACKGROUND
  HLA 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.
  
  
  RESULTS
  The 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
  These 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.
authors.affiliation: Department of Microbiology, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: Gathsaurie Neelika
authors.initials: GN
authors.lastname: Malavige
authors.forename: Tim
authors.initials: T
authors.lastname: Rostron
authors.forename: Lochana T
authors.initials: LT
authors.lastname: Rohanachandra
authors.forename: S D
authors.initials: SD
authors.lastname: Jayaratne
authors.forename: Neluka
authors.initials: N
authors.lastname: Fernando
authors.forename: Aruna Dharshan
authors.initials: AD
authors.lastname: De Silva
authors.forename: Malaka
authors.initials: M
authors.lastname: Liyanage
authors.forename: Graham
authors.initials: G
authors.lastname: Ogg
mesh_terms: D000483:Alleles; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology*; D013188:Sri Lanka
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II