KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.

Abstract

Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P< 0.001), and HC (10%) (crude OR,12.38; P< 0.001). Similar results were obtained for the HLA-C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P< 0.10), and HC (60%) (crude OR, 3.56; P< 0.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR,0.10; P< 0.05). These results suggest a detrimental role of HLA-A-Bw4 and HLA-C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%), and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection