Natural killer cell receptor variants and chronic hepatitis B virus infection in the Vietnamese population

• Published in: International journal of infectious diseases Vol. 96; pp. 541 - 547
• Main Authors: Auer, Eduardo Delabio, Tong, Hoang Van, Amorim, Leonardo Maldaner, Malheiros, Danielle, Hoan, Nghiem Xuan, Issler, Hellen Caroline, Petzl-Erler, Maria Luiza, Beltrame, Márcia Holsbach, Boldt, Angelica Beate Winter, Toan, Nguyen Linh, Song, Le Huu, Velavan, Thirumalaisamy P., Augusto, Danillo G.
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01-07-2020; Elsevier
• Subjects: Hepatitis B virus; Hepatocellular carcinoma; Human leukocyte antigen; Killer-cell immunoglobulin-like receptor; Liver cirrhosis; Natural killer cells; Hepatocellular carcinoma; Natural killer cells; Hepatitis B virus; Killer-cell immunoglobulin-like receptor; Liver cirrhosis; Human leukocyte antigen; HLA; KIR; hepatitis B virus; hepatocellular carcinoma; liver cirrhosis; NK cell
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2020.05.033

•Variations in natural killer cell receptors affect the risk of hepatitis B virus (HBV) and clinical outcomes.•Variation in KIR2DS4 is associated with a risk to chronic HBV.•Combinations of killer-cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) ligands protect from chronic HBV and liver cirrhosis.•Activating KIR protects HBV patients from hepatocellular carcinoma.
Genes of host immunity play an important role in disease pathogenesis and are determinants of clinical courses of infections, including hepatitis B virus (HBV). Killer-cell immunoglobulin-like receptor (KIR), expressed on the surface of natural killer cells (NK), regulate NK cell cytotoxicity by interacting with human leukocyte antigen (HLA) class I molecules and are candidates for influencing the course of HBV. This study evaluated whether variations in KIR gene content and HLA-C ligands are associated with HBV and with the development of liver cirrhosis and hepatocellular carcinoma.
A Vietnamese study cohort (HBV n = 511; controls n = 140) was genotyped using multiplex sequence-specific polymerase chain reaction (PCR-SSP) followed by melting curve analysis.
The presence of the functional allelic group of KIR2DS4 was associated with an increased risk of chronic HBV (OR = 1.86, pcorr = 0.02), while KIR2DL2+HLA-C1 (OR = 0.62, pcorr = 0.04) and KIR2DL3+HLA-C1 (OR = 0.48, pcorr = 0.04) were associated with a decreased risk. The pair KIR2DL3+HLA-C1 was associated with liver cirrhosis (OR = 0.40, pcorr = 0.01). The presence of five or more activating KIR variants was associated with hepatocellular carcinoma (OR = 0.53, pcorr = 0.04).
KIR gene content variation and combinations KIR-HLA influence the outcome of HBV infection.