The immunoglobulin γ marker 17 allotype and KIR/HLA genes prevent the development of chronic hepatitis B in humans

Immunology. 2020 Feb;159(2):178-182. doi: 10.1111/imm.13133. Epub 2019 Nov 12.


Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the patients with CHB with those who resolved HBV infection showed that the presence of GM17 allele virtually eliminated the risk of developing CHB (OR, 0·03; 95% CI, 0·004-0·16; P < 0·0001). In addition, the combination of GM17, KIR2DL3, HLA-A-Bw4 and HLA-C2 was highly sensitive to predict the outcome of HBV infection.

Keywords: hepatitis B virus; human leucocyte antigen; killer immunoglobulin-like receptor; γ marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-B Antigens / genetics*
  • HLA-B Antigens / immunology
  • HLA-C Antigens / genetics*
  • HLA-C Antigens / immunology
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / prevention & control*
  • Host-Pathogen Interactions
  • Humans
  • Immunoglobulin Gm Allotypes / genetics*
  • Immunoglobulin Gm Allotypes / immunology
  • Phenotype
  • Protective Factors
  • Receptors, KIR2DL3 / genetics*
  • Receptors, KIR2DL3 / immunology
  • Risk Assessment
  • Risk Factors


  • HLA-B Antigens
  • HLA-C Antigens
  • Immunoglobulin Gm Allotypes
  • KIR2DL3 protein, human
  • Receptors, KIR2DL3