Is Hepatitis B Virus clearance associated with Natural killer inhibitory receptor and/or with their ligands; human leukocyte antigens genes

 

Dr. Rifaat Safadi

Hepatitis B -virus (HBV) infection range from asymptomatic, disease and virus clearance to chronic infection that may lead to cirrhosis, liver failure or hepatocellular carcinoma (HCC).  This outcome is interplay between the innate and adaptive immune system in which NK and T lymphocytes are the major components. Activity of NK cells is controlled in part by ligation of some human leukocyte antigens (HLA-Class I) with immunoglobulin like inhibitory and activating receptors (KIRs). In the proposed project, we will investigate the distribution and polymorphism of KIR and HLA genes in HBV infected Palestinians and Qatari's individuals in two categories of patients, those with HBV infection followed by clearance and those with viral persistence. To study the distribution and polymorphism of KIR genes and of receptors and of their ligands; the HLA class-I alleles in the pathogenesis of HBV infection will be evaluated in the Arabic population and will be compared to healthy control group. This will be done in Palestinians and Qatar populations to assess the genetic distance between both groups as compared to other ethnic groups.  In addition, we will investigate the association of KIR genes and or/ receptors and their ligand the HLA-C and Bw with HBV viral clearance or persistence. Specifically, we will explore if there is a selective alteration, in KIR gene numbers, KIR receptor expression, in peripheral blood vs. NK cells in the liver of patients with chronic infections and HCC.