The KIR-ligand HLA-A Bw4 predicts the outcome of hepatitis B infection.

Abstract

Killer Immunoglobulin like Receptors (KIR) are membrane proteins expressed on Natural Killer (NK) cells and on a small subset of CD8 lymphocytes. They influence the activation or inhibition of both cell types through interaction with their ligands, represented by Human Leukocyte Antigen (HLA) class I molecules. Several studies have shown that KIR/HLA interactions are involved in the pathogenesis and progression of different diseases as viral infections, autoimmune-disorders, or cancer, conditioning susceptibly to or protection against the outcome of the disease. HBV infection represents a major health problem with 2 billion people infected and 3 hundred and fifty million people with chronic diseases worldwide. The aim of this study is to assess whether KIR/HLA interaction is involved in immune response against hepatitis B infection. We are conducting a case-control study in Sicilian population, comparing subjects with chronic hepatitis B with subjects with previous HBV infection (HBc-Ab with or without HBeAb or HBsAb) as controls. A second control population was represented by HBcAb negative subjects. Peripheral blood samples were collected and genomic DNA was extracted from leukocytes and typed, using PCR-SSP, for KIR and HLA Preliminary data showed that HLA-A Bw4 was more frequent in cases than controls (1. cases, 23/35, 66%, vs. HBcAb positive controls, 8/35, 23%, OR 6.47, p=0.0003, and 2. cases, 23/35, 66%, vs. HBcAb negative controls, 6/60, 10%, OR 17.25, p=0.00001). No difference have been found in the frequencies HLA-C1, HLA-C2, HLA-Bw4I, and HLA-Bw4T; no difference have also been reported in the number of KIRs, both activating and inhibitory, and haplotype A and B between groups. Our data suggest that the HLA-A Bw4, likely through its interaction with the inhibitory KIR3DL1, is associated to the risk of developing chronic hepatitis B. Data on HBcAb negative subjects suggest also the possibility of selective genetic pressure.