Piotr Kuśnierczyk1, Iwona Mozer-Lisewska2, Katarzyna Zwolińska3, Arleta Elżbieta Kowala-Piaskowska2, Maciej Bura2, Iwona Bereszyńska2, Anna Pauli2, Jan Żeromski4. 1. Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. Electronic address: pkusnier@iitd.pan.wroc.pl. 2. Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland. 3. Laboratory of Virology, Department of Immunology of Infectious Diseases, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. 4. Chair of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
Abstract
BACKGROUND: Natural killer (NK) cells are an important element of innate immunity against viruses, although their numbers decrease in the liver during chronic HCV infection. NK cells express a large panel of inhibitory and activating receptors. The most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which are encoded by multiple genes that may be present or absent in given individuals depending on their genotype. This variability results in differential susceptibility to viral infections and diseases, including HCV infection and its consequences. AIMS AND METHODS: The aim of this study was to test whether chronical infection with HCV and the viremia levels are associated with any KIR gene in the Polish population. We typed 301 chronically HCV-infected patients and 425 non-infected healthy individuals for the presence or absence of KIR genes and their ligands, HLA-C C1 and C2 groups as well as HLA-B and HLA-A Bw4-positive alleles. RESULTS: We found that males, but not females, possessing KIR2DS2 and KIR2DL2 genes had a 1.7 higher probability to become chronically HCV-infected than males negative for these genes (p=0.0213). In accord with this, centromeric B region, containing KIR2DS2 and KIR2DL2 genes, was also associated with chronic HCV infection in males. In addition, patients of both genders possessing KIR2DS3 but not KIR2DS5 gene exhibited, on average, 2.6 lower level of viremia than HCV-infected individuals with other genotypes (p=0.00282). This was evident in those infected at a young age. KIR2DS3-positive patients also had lower mean levels of bilirubin than KIR2DS3-negative ones (p=0.02862). CONCLUSION: Our results suggest a contribution of the KIR2DS2 and KIR2DL2 genes (cenB haplotype) to the susceptibility to chronic HCV infection, and an association of the KIR2DS3 gene in the absence of KIR2DS5 with low viremia levels.
BACKGROUND: Natural killer (NK) cells are an important element of innate immunity against viruses, although their numbers decrease in the liver during chronic HCV infection. NK cells express a large panel of inhibitory and activating receptors. The most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which are encoded by multiple genes that may be present or absent in given individuals depending on their genotype. This variability results in differential susceptibility to viral infections and diseases, including HCV infection and its consequences. AIMS AND METHODS: The aim of this study was to test whether chronical infection with HCV and the viremia levels are associated with any KIR gene in the Polish population. We typed 301 chronically HCV-infectedpatients and 425 non-infected healthy individuals for the presence or absence of KIR genes and their ligands, HLA-C C1 and C2 groups as well as HLA-B and HLA-A Bw4-positive alleles. RESULTS: We found that males, but not females, possessing KIR2DS2 and KIR2DL2 genes had a 1.7 higher probability to become chronically HCV-infected than males negative for these genes (p=0.0213). In accord with this, centromeric B region, containing KIR2DS2 and KIR2DL2 genes, was also associated with chronic HCV infection in males. In addition, patients of both genders possessing KIR2DS3 but not KIR2DS5 gene exhibited, on average, 2.6 lower level of viremia than HCV-infected individuals with other genotypes (p=0.00282). This was evident in those infected at a young age. KIR2DS3-positive patients also had lower mean levels of bilirubin than KIR2DS3-negative ones (p=0.02862). CONCLUSION: Our results suggest a contribution of the KIR2DS2 and KIR2DL2 genes (cenB haplotype) to the susceptibility to chronic HCV infection, and an association of the KIR2DS3 gene in the absence of KIR2DS5 with low viremia levels.
Authors: Katarzyna Zwolińska; Olga Błachowicz; Tomasz Tomczyk; Brygida Knysz; Jacek Gąsiorowski; Małgorzata Zalewska; Beata U Orzechowska; Marta Sochocka; Egbert Piasecki Journal: Immunogenetics Date: 2016-02-18 Impact factor: 2.846