title: Association of MICA and MICB alleles with symptomatic dengue infection.
abstract: Dengue viruses (DV) are one of the most important arthropod-borne viral diseases in the developing world. DV can cause syndromes that are either self-limiting or severe. Allelic variants of human leukocyte antigen (HLA) genes have been demonstrated to be associated with disease susceptibility. Here we report the association of nonclassical HLA class I MICA-MICB genes with disease outcome during DV infection. A sequencing-based typing method and genotyping of MICA and MICB in a well-characterized group of Cuban individuals with dengue hemorrhagic fever (DHF), dengue fever (DF), or asymptomatic dengue infection (ADI) was performed. Statistical analysis revealed a tendency for MICA*008 and MICB*008 to associate with susceptibility to illness when symptomatic versus asymptomatic cases (odds ratio [OR] = 2.1, p(v) = 0.03, and OR = 10.4, p = 0.0096, respectively) were compared. Surprisingly, a stronger association of both allelic forms was observed for the DF patients compared with the ADI group (MICA*008, OR = 5.2, p = 0.0001; and MICB*008, OR = 13.2, p = 0.0025) rather than the severe cases. Major histocompatibility class I-related gene-related natural killer cells and/or γδ and αβ T-cell activation might regulate the development of symptomatic DF and DHF.
authors.affiliation: Department of Virology, Tropical Medicine Institute Pedro Kourí, Habana, Cuba.
authors.forename: Gissel
authors.initials: G
authors.lastname: García
authors.forename: Florencia
authors.initials: F
authors.lastname: del Puerto
authors.forename: Ana B
authors.initials: AB
authors.lastname: Pérez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sierra
authors.forename: Eglys
authors.initials: E
authors.lastname: Aguirre
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Lizet
authors.initials: L
authors.lastname: Sánchez
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
authors.forename: María G
authors.initials: MG
authors.lastname: Guzmán
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D058345:Asymptomatic Infections; D003462:Cuba / Q000453:epidemiology; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D011110:Polymorphism, Genetic; D019595:Severe Dengue / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000821:virology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen