title: Protective and enhancing HLA alleles, HLA-DRB1*0901 and HLA-A*24, for severe forms of dengue virus infection, dengue hemorrhagic fever and dengue shock syndrome.
abstract: BACKGROUND
  Dengue virus (DV) infection is one of the most important mosquito-borne diseases in the tropics. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. Protective and/or pathogenic T cell immunity is supposed to be important in the pathogenesis of DHF and DSS.
  
  
  RESULTS
  To identify HLA alleles controlling T cell immunity against dengue virus (DV), we performed a hospital-based case control study at Children's Hospital No.2, Ho Chi Minh City (HCMC), and Vinh Long Province Hospital (VL) in Southern Vietnam from 2002 to 2005. A total of 211 and 418 patients with DHF and DSS, respectively, diagnosed according to the World Health Organization (WHO) criteria, were analyzed for their characteristic HLA-A, -B and -DRB1 alleles. Four hundred fifty healthy children (250 from HCMC and 200 from VL) of the same Kinh ethnicity were also analyzed as population background. In HLA class I, frequency of the HLA-A*24 showed increased tendency in both DHF and DSS patients, which reproduced a previous study. The frequency of A*24 with histidine at codon 70 (A*2402/03/10), based on main anchor binding site specificity analysis in DSS and DHF patients, was significantly higher than that in the population background groups (HCMC 02-03 DSS: OR = 1.89, P = 0.008, DHF: OR = 1.75, P = 0.033; VL 02-03 DSS: OR = 1.70, P = 0.03, DHF: OR = 1.46, P = 0.38; VL 04-05 DSS: OR = 2.09, P = 0.0075, DHF: OR = 2.02, P = 0.038). In HLA class II, the HLA-DRB1*0901 frequency was significantly decreased in secondary infection of DSS in VL 04-05 (OR = 0.35, P = 0.0025, Pc = 0.03). Moreover, the frequency of HLA-DRB1*0901 in particular was significantly decreased in DSS when compared with DHF in DEN-2 infection (P = 0.02).
  
  
  CONCLUSIONS
  This study improves our understanding of the risk of HLA-class I for severe outcome of DV infection in the light of peptide anchor binding site and provides novel evidence that HLA-class II may control disease severity (DHF to DSS) in DV infection.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
authors.forename: Thi Phuong Lan
authors.initials: TP
authors.lastname: Nguyen
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Thi Que Huong
authors.initials: TQ
authors.lastname: Vu
authors.forename: Quang Ha
authors.initials: QH
authors.lastname: Do
authors.forename: Thi Thuy
authors.initials: TT
authors.lastname: Tran
authors.forename: Dinh Tham
authors.initials: DT
authors.lastname: Vo
authors.forename: Manh Tuan
authors.initials: MT
authors.lastname: Ha
authors.forename: Van Tuong
authors.initials: VT
authors.lastname: Vo
authors.forename: Thi Phi Nga
authors.initials: TP
authors.lastname: Cao
authors.forename: Van Dat
authors.initials: VD
authors.lastname: Tran
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Oyama
authors.forename: Kouichi
authors.initials: K
authors.lastname: Morita
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003716:Dengue Virus / Q000302:isolation & purification / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007223:Infant; D008297:Male; D019595:Severe Dengue / Q000235:genetics* / Q000276:immunology* / Q000821:virology
chemical_list: D015234:HLA-A Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains