title: Association between HLA class I and class II alleles and the outcome of West Nile virus infection: an exploratory study.
abstract: BACKGROUND
  West Nile virus (WNV) infection is asymptomatic in most individuals, with a minority developing symptoms ranging from WNV fever to serious neuroinvasive disease. This study investigated the impact of host HLA on the outcome of WNV disease.
  
  
  METHODS
  A cohort of 210 non-Hispanic mostly white WNV(+) subjects from Canada and the U.S. were typed for HLA-A, B, C, DP, DQ, and DR. The study subjects were divided into three WNV infection outcome groups: asymptomatic (AS), symptomatic (S), and neuroinvasive disease (ND). Allele frequency distribution was compared pair-wise between the AS, S, and ND groups using χ2 and Fisher's exact tests and P values were corrected for multiple comparisons (Pc). Allele frequencies were compared between the groups and the North American population (NA) used as a control group. Logistic regression analysis was used to evaluate the potential synergistic effect of age and HLA allele phenotype on disease outcome.
  
  
  RESULTS
  The alleles HLA-A*68, C*08 and DQB*05 were more frequently associated with severe outcomes (ND vs. AS, P(A*68) = 0.013/Pc = 0.26, P(C*08) = 0.0075/Pc = 0.064, and P(DQB1*05) = 0.029/Pc = 0.68), However the apparent DQB1*05 association was driven by age. The alleles HLA-B*40 and C*03 were more frequently associated with asymptomatic outcome (AS vs. S, P(B*40) = 0.021/Pc = 0.58 and AS vs. ND P(C*03) = 0.039/Pc = 0.64) and their frequencies were lower within WNV(+) subjects with neuroinvasive disease than within the North American population (NA vs. S, P(B*40) = 0.029 and NA vs. ND, P(C*03) = 0.032).
  
  
  CONCLUSIONS
  Host HLA may be associated with the outcome of WNV disease; HLA-A*68 and C*08 might function as "susceptible" alleles, whereas HLA-B*40 and C*03 might function as "protective" alleles.
authors.affiliation: Blood Systems Research Institute, San Francisco, California, United States of America. mlanteri@bloodsystems.org
authors.forename: Marion C
authors.initials: MC
authors.lastname: Lanteri
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Kaidarova
authors.forename: Trevor
authors.initials: T
authors.lastname: Peterson
authors.forename: Steven
authors.initials: S
authors.lastname: Cate
authors.forename: Brian
authors.initials: B
authors.lastname: Custer
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wu
authors.forename: Maria
authors.initials: M
authors.lastname: Agapova
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Law
authors.forename: Thomas
authors.initials: T
authors.lastname: Bielawny
authors.forename: Frank
authors.initials: F
authors.lastname: Plummer
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Tobler
authors.forename: Mark
authors.initials: M
authors.lastname: Loeb
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bramson
authors.forename: Ma
authors.initials: M
authors.lastname: Luo
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D014901:West Nile Fever / Q000235:genetics* / Q000503:physiopathology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II