Major Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais

J Infect Dis. 2020 Aug 4;222(5):840-846. doi: 10.1093/infdis/jiaa134.


Background: Major histocompatibility complex class I chain-related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness.

Methods: MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease.

Results: MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18-8.84] and 1.99 [1.07-2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI, .21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI, .22-.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI, .14-.60).

Conclusions: Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells.

Keywords: MICA; MICB; Thais; allele; associations; dengue; gene; haplotype; infections; secondary.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Alleles
  • Asian People / genetics*
  • Child
  • Child, Preschool
  • Genes, MHC Class I / genetics*
  • Genetic Predisposition to Disease*
  • HLA-B18 Antigen / genetics
  • HLA-B40 Antigen / genetics
  • HLA-B44 Antigen / genetics
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Linkage Disequilibrium / genetics
  • Protective Factors
  • Severe Dengue / genetics*
  • Thailand / ethnology


  • HLA-B18 Antigen
  • HLA-B40 Antigen
  • HLA-B44 Antigen
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • MICB antigen