Human leukocyte antigen class-I variation is associated with atopic dermatitis: A case-control study

Hum Immunol. 2021 Aug;82(8):593-599. doi: 10.1016/j.humimm.2021.04.001. Epub 2021 Apr 17.


Atopic dermatitis (AD) is a common immune-medicated skin disease. Previous studies have explored the relationship between Human Leukocyte Antigen (HLA) allelic variation and AD with conflicting results. The aim was to examine HLA Class I genetic variation, specifically peptide binding groove variation, and associations with AD. A case-control study was designed to evaluate HLA class I allelic variation and binding pocket polymorphisms, using next generation sequencing on 464 subjects with AD and 388 without AD. Logistic regression was used to evaluate associations with AD by estimating odds ratios (95% confidence intervals). Significant associations were noted with susceptibility to AD (B*53:01) and protection from AD (A*01:01, A*02:01, B*07:02 and C*07:02). Evaluation of polymorphic residues in Class I binding pockets revealed six amino acid residues conferring protection against AD: A9F (HLA-A, position 9, phenylalanine) [pocket B/C], A97I [pocket C/E], A152V [pocket E], A156R [pocket D/E], B163E [pocket A] and C116S [pocket F]. These findings demonstrate that specific HLA class I components are associated with susceptibility or protection from AD. Individual amino acid residues are relevant to protection from AD and set the foundation for evaluating potential HLA Class I molecules in complex with peptides/antigens that may initiate or interfere with T-cell responses.

Keywords: Allergy; Atopic dermatitis; Case-control study; Human leukocyte antigen.

MeSH terms

  • Alleles
  • Case-Control Studies
  • Dermatitis, Atopic / diagnosis
  • Dermatitis, Atopic / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Models, Molecular
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Protein Conformation
  • Sequence Analysis, DNA
  • Structure-Activity Relationship


  • Histocompatibility Antigens Class I