Skip to main content
Top
Published in: Inflammation 5/2013

Open Access 01-10-2013

Alterations in NK Cell Phenotype in Relation to Liver Steatosis in Children with Chronic Hepatitis C

Authors: Anna Mania, Mariusz Kaczmarek, Paweł Kemnitz, Iwona Mozer-Lisewska, Jan Sikora, Magdalena Figlerowicz, Aldona Woźniak, Katarzyna Mazur-Melewska, Wojciech Służewski, Jan Żeromski

Published in: Inflammation | Issue 5/2013

Login to get access

Abstract

NK cells were found to play an important role in liver fibrosis, a process commonly seen in a chronic liver disease such as chronic hepatitis C (CHC). The aim of this study was to evaluate potential differences in relation to coexisting liver steatosis in children with chronic hepatitis C. The study group consisted of 31 children with chronic hepatitis, aged 7–18 years (mean = 15 ± 2 years). Blood samples were taken prior to liver biopsy. The METAVIR scale was used for histological evaluation. Peripheral lymphocytes were subjected to monoclonal antibodies to CD56 antigen, KIRs and NKG2D antigens. Cells were assayed by flow cytometry for the ratio of positive cells and mean fluorescence intensity (MFI). Results were evaluated regarding the presence of liver steatosis. Significantly higher mean AST activity as well as higher AST-to-platelets ratio index (APRI) was observed in a group of children with coexisting liver steatosis. These children had significantly higher MFI for CD158e and lower MFI for NKG2D. All CHC patients had significantly higher MFI for NKG2D than the controls. The proportion of cells with expression of CD158i, KIR2D and APRI was found independent predictors of liver steatosis in univariate analysis and body mass index in logistic regression. The expression of NK cell receptors is altered in coexisting steatosis that may influence long-term prognosis in CHC.
Literature
1.
go back to reference Mania, A., P. Kemnitz, M. Figlerowicz, I. Mozer-Lisewska, A. Kowala-Piaskowska, A. Woźniak, and W. Służewski. 2012. Clinical picture and liver histology of chronic hepatitis C in children. Infectious Diseases in Clinical Practice 20: 141–147.CrossRef Mania, A., P. Kemnitz, M. Figlerowicz, I. Mozer-Lisewska, A. Kowala-Piaskowska, A. Woźniak, and W. Służewski. 2012. Clinical picture and liver histology of chronic hepatitis C in children. Infectious Diseases in Clinical Practice 20: 141–147.CrossRef
2.
go back to reference Moretta, L., G. Ferlazzo, C. Bottino, M. Vitale, D. Pende, M.C. Mingari, and A. Moretta. 2006. Effector and regulatory events during natural killer-dendritic cell interactions. Immunology Reviews 214: 219–228.CrossRef Moretta, L., G. Ferlazzo, C. Bottino, M. Vitale, D. Pende, M.C. Mingari, and A. Moretta. 2006. Effector and regulatory events during natural killer-dendritic cell interactions. Immunology Reviews 214: 219–228.CrossRef
3.
go back to reference Doherty, D.G., S. Norris, L. Madrigal-Estebas, G. McEntee, O. Traynor, J.E. Hegarty, and C. O’Farrelly. 1999. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. Journal of Immunology 163: 2314–2321. Doherty, D.G., S. Norris, L. Madrigal-Estebas, G. McEntee, O. Traynor, J.E. Hegarty, and C. O’Farrelly. 1999. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. Journal of Immunology 163: 2314–2321.
4.
go back to reference Varchetta, S., D. Mele, S. Mantovani, B. Oliviero, E. Cremonesi, S. Ludovisi, G. Michelone, M. Alesani, R. Rosati, M. Montorsi, and M.U. Mondelli. 2012. Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection. Hepatology 56: 841–9.PubMedCrossRef Varchetta, S., D. Mele, S. Mantovani, B. Oliviero, E. Cremonesi, S. Ludovisi, G. Michelone, M. Alesani, R. Rosati, M. Montorsi, and M.U. Mondelli. 2012. Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection. Hepatology 56: 841–9.PubMedCrossRef
5.
go back to reference Bauer, S., V. Groh, J. Wu, A. Steinle, J.H. Phillips, L.L. Lanier, and T. Spies. 1999. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285: 727–729.PubMedCrossRef Bauer, S., V. Groh, J. Wu, A. Steinle, J.H. Phillips, L.L. Lanier, and T. Spies. 1999. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285: 727–729.PubMedCrossRef
6.
go back to reference Oliviero, B., S. Varchetta, E. Paudice, G. Michelone, M. Zaramella, D. Mavillo, F. De Filippi, S. Bruno, and M.U. Mondelli. 2009. Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology 137: 1151–1160.PubMedCrossRef Oliviero, B., S. Varchetta, E. Paudice, G. Michelone, M. Zaramella, D. Mavillo, F. De Filippi, S. Bruno, and M.U. Mondelli. 2009. Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology 137: 1151–1160.PubMedCrossRef
7.
go back to reference Radaeva, S., R. Sun, B. Jaruga, V.T. Nguyen, Z. Tian, and B. Gao. 2006. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis-factor related apoptosis-inducing ligand-dependent manners. Gastroenterology 130: 435–452.PubMedCrossRef Radaeva, S., R. Sun, B. Jaruga, V.T. Nguyen, Z. Tian, and B. Gao. 2006. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis-factor related apoptosis-inducing ligand-dependent manners. Gastroenterology 130: 435–452.PubMedCrossRef
8.
go back to reference Livingstone, S.E., H. Deubner, D.L. Burden, B.J. McMahon, C.E. Homan, L.J. Townshend-Bulson, M.G. Bruce, T.W. Hennessy, J.L. Wiliams, and D.R. Gretch. 2010. Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C. Canadian Journal of Gastroenterology 24: 445–451. Livingstone, S.E., H. Deubner, D.L. Burden, B.J. McMahon, C.E. Homan, L.J. Townshend-Bulson, M.G. Bruce, T.W. Hennessy, J.L. Wiliams, and D.R. Gretch. 2010. Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C. Canadian Journal of Gastroenterology 24: 445–451.
9.
go back to reference Fukasawa, M., Y. Tanaka, S. Sato, Y. Ono, Y. Nitahara-Kasahara, T. Suzuki, T. Miyamura, K. Hanada, and M. Nishijima. 2006. Enhancement of de novo fatty acid biosynthesis in hepatic cell line Huh7 expressing hepatitis C virus core protein. Biological and Pharmaceutical Bulletin 29: 1958–1961.PubMedCrossRef Fukasawa, M., Y. Tanaka, S. Sato, Y. Ono, Y. Nitahara-Kasahara, T. Suzuki, T. Miyamura, K. Hanada, and M. Nishijima. 2006. Enhancement of de novo fatty acid biosynthesis in hepatic cell line Huh7 expressing hepatitis C virus core protein. Biological and Pharmaceutical Bulletin 29: 1958–1961.PubMedCrossRef
10.
go back to reference Okuda, M., K. Li, M.R. Beard, L.A. Showalter, F. Scholle, S.M. Lemon, and S.A. Weinman. 2002. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122: 366–375.PubMedCrossRef Okuda, M., K. Li, M.R. Beard, L.A. Showalter, F. Scholle, S.M. Lemon, and S.A. Weinman. 2002. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122: 366–375.PubMedCrossRef
11.
go back to reference Lonardo, A., S. Ballestri, L.E. Adinolfi, E. Violi, L. Carulli, S. Lombardini, F. Scaglioni, M. Ricchi, G. Ruggiero, and P. Loria. 2009. Hepatitis C virus infected patients are ‘spared’ from the metabolic syndrome but not from insulin resistance. A comparative study of nonalcoholic fatty liver disease and hepatitis C virus-related steatosis. Canadian Journal of Gastroenterology 23(4): 273–278.PubMed Lonardo, A., S. Ballestri, L.E. Adinolfi, E. Violi, L. Carulli, S. Lombardini, F. Scaglioni, M. Ricchi, G. Ruggiero, and P. Loria. 2009. Hepatitis C virus infected patients are ‘spared’ from the metabolic syndrome but not from insulin resistance. A comparative study of nonalcoholic fatty liver disease and hepatitis C virus-related steatosis. Canadian Journal of Gastroenterology 23(4): 273–278.PubMed
12.
go back to reference Adinolfi, L.E., M. Gambardella, A. Andreana, M.F. Tripodi, R. Utili, and G. Ruggiero. 2001. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 33: 1358–1364.PubMedCrossRef Adinolfi, L.E., M. Gambardella, A. Andreana, M.F. Tripodi, R. Utili, and G. Ruggiero. 2001. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 33: 1358–1364.PubMedCrossRef
13.
go back to reference Wai, C.T., J.K. Greenson, R.J. Fontana, J.D. Kalbfleisch, J.A. Marrero, H.S. Conjeevaram, and A.S. Lok. 2003. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38: 518–526.PubMedCrossRef Wai, C.T., J.K. Greenson, R.J. Fontana, J.D. Kalbfleisch, J.A. Marrero, H.S. Conjeevaram, and A.S. Lok. 2003. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38: 518–526.PubMedCrossRef
14.
go back to reference Delgado-Borrego, A., D. Healey, B. Negre, M. Christofi, S. Sabharwal, D.A. Ludwiga, T. Raymond, R.T. Chung, and M.M. Jonas. 2010. The influence of body mass index on outcome of pediatric chronic hepatitis C virus infection. Journal of Pediatric Gastroenterology and Nutrition 51: 191–197.PubMedCrossRef Delgado-Borrego, A., D. Healey, B. Negre, M. Christofi, S. Sabharwal, D.A. Ludwiga, T. Raymond, R.T. Chung, and M.M. Jonas. 2010. The influence of body mass index on outcome of pediatric chronic hepatitis C virus infection. Journal of Pediatric Gastroenterology and Nutrition 51: 191–197.PubMedCrossRef
15.
go back to reference Kremer, M., I.N. Hines, R.J. Milton, and M.D. Wheeler. 2006. Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell-mediated hepatitis. Hepatology 44: 216–227.PubMedCrossRef Kremer, M., I.N. Hines, R.J. Milton, and M.D. Wheeler. 2006. Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell-mediated hepatitis. Hepatology 44: 216–227.PubMedCrossRef
16.
go back to reference Wen, C., X. He, H. Ma, N. Hou, C. Wei, T. Song, Y. Zhang, L. Sun, Q. Ma, and H. Zhong. 2008. Hepatitis C virus infection downregulates the ligands of the activating receptor NKG2D. Cellular & Molecular Immunology 5: 475–478.CrossRef Wen, C., X. He, H. Ma, N. Hou, C. Wei, T. Song, Y. Zhang, L. Sun, Q. Ma, and H. Zhong. 2008. Hepatitis C virus infection downregulates the ligands of the activating receptor NKG2D. Cellular & Molecular Immunology 5: 475–478.CrossRef
17.
go back to reference Castriconi, R., C. Cantoni, M. Della Chiesa, M. Vitale, E. Marcenaro, R. Conte, R. Biassoni, C. Bottino, L. Moretta, and A. Morreta. 2003. Transforming growth factor beta1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proceedings of the National Academy of Science of the Unite States of America 100: 4120–4125.CrossRef Castriconi, R., C. Cantoni, M. Della Chiesa, M. Vitale, E. Marcenaro, R. Conte, R. Biassoni, C. Bottino, L. Moretta, and A. Morreta. 2003. Transforming growth factor beta1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proceedings of the National Academy of Science of the Unite States of America 100: 4120–4125.CrossRef
18.
go back to reference Suppiah, V., S. Gauderi, N.J. Armstrong, K.S. O’Connor, T. Berg, M. Weltman, M.L. Abate, U. Spengler, M. Bassedine, G.J. Dore, W.L. Irving, E. Powell, M. Hellard, S. Riodan, G. Matthews, D. Sheridan, J. Natterman, A. Smedile, T. Muller, E. Hammond, D. Dunn, F. Negro, P.Y. Bochud, S. Mallal, G. Ahlenstiel, G.J. Stewart, J. George, D.R. Booth, and International Hepatitis C Genetics Consortium (IHCGC). 2011. IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. PLoS Med. 8: e1001092.PubMedCrossRef Suppiah, V., S. Gauderi, N.J. Armstrong, K.S. O’Connor, T. Berg, M. Weltman, M.L. Abate, U. Spengler, M. Bassedine, G.J. Dore, W.L. Irving, E. Powell, M. Hellard, S. Riodan, G. Matthews, D. Sheridan, J. Natterman, A. Smedile, T. Muller, E. Hammond, D. Dunn, F. Negro, P.Y. Bochud, S. Mallal, G. Ahlenstiel, G.J. Stewart, J. George, D.R. Booth, and International Hepatitis C Genetics Consortium (IHCGC). 2011. IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. PLoS Med. 8: e1001092.PubMedCrossRef
19.
go back to reference Golden-Mason, L., K.M. Bambha, L. Cheng, C.D. Howell, M.W. Taylor, P.J. Clark, N. Afidhal, H.R. Rosen, and Virahep-C Study Group. 2011. Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C. Hepatology 54: 1559–1569.PubMedCrossRef Golden-Mason, L., K.M. Bambha, L. Cheng, C.D. Howell, M.W. Taylor, P.J. Clark, N. Afidhal, H.R. Rosen, and Virahep-C Study Group. 2011. Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C. Hepatology 54: 1559–1569.PubMedCrossRef
Metadata
Title
Alterations in NK Cell Phenotype in Relation to Liver Steatosis in Children with Chronic Hepatitis C
Authors
Anna Mania
Mariusz Kaczmarek
Paweł Kemnitz
Iwona Mozer-Lisewska
Jan Sikora
Magdalena Figlerowicz
Aldona Woźniak
Katarzyna Mazur-Melewska
Wojciech Służewski
Jan Żeromski
Publication date
01-10-2013
Publisher
Springer US
Published in
Inflammation / Issue 5/2013
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-013-9632-0

Other articles of this Issue 5/2013

Inflammation 5/2013 Go to the issue