Implications of genome-wide association studies in novel therapeutics in primary biliary cirrhosis

European Journal of Immunology

Volumn 44, Issue 4, 2014, Pages 945-954

  Carbone, Marco ^a,b   Lleo, Ana ^c   Sandford, Richard N ^b   Invernizzi, Pietro ^c,d  

^a ADDENBROOKE S HOSPITAL   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Autoimmunity; Genetics; Liver immunology

Indexed keywords

ABATACEPT; ADALIMUMAB; CERTOLIZUMAB PEGOL; CYCLOPAMINE; ETANERCEPT; GOLIMUMAB; INFLIXIMAB; INTERLEUKIN 12; INTERLEUKIN 23; PHOSPHATIDYLINOSITOL; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; AUTOIMMUNE DISEASE; BILE DUCT INJURY; DISEASE CLASSIFICATION; GENETIC ASSOCIATION; HUMAN; INFLAMMATION; NONHUMAN; PHARMACOGENETICS; PRIMARY BILIARY CIRRHOSIS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

AUTOIMMUNITY; GENETICS; LIVER IMMUNOLOGY;

GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; LIVER CIRRHOSIS, BILIARY; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS; SIGNAL TRANSDUCTION; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84898011122     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201344270     Document Type: Article

References (85)

1. Invernizzi, P., Selmi, C. and Gershwin, M. E., Update on primary biliary cirrhosis. Dig. Liver. Dis. 2010. 42: 401-408.
2. Tsuda, M., Zhang, W., Yang, G. X., Tsuneyama, K., Ando, Y., Kawata, K., Park, O. et al., Deletion of interleukin (IL)-12p35 induces liver fibrosis in dominant-negative TGFbeta receptor type II mice. Hepatology 2013. 57: 806-816.
3. Ando, Y., Yang, G. X., Tsuda, M., Kawata, K., Zhang, W., Nakajima, T., Tsuneyama, K. et al., The immunobiology of colitis and cholangitis in interleukin-23p19 and interleukin-17A deleted dominant negative form of transforming growth factor beta receptor type II mice. Hepatology 2012. 56: 1418-1426.
4. Lleo, A. and Invernizzi, P., Apotopes and innate immune system: novel players in the primary biliary cirrhosis scenario. Dig. Liver. Dis. 2013. 45: 630-636.
5. Podda, M., Selmi, C., Lleo, A., Moroni, L. and Invernizzi, P., The limitations and hidden gems of the epidemiology of primary biliary cirrhosis. J. Autoimmun. 2013. 46: 81-87.
6. Tsuda, M., Moritoki, Y., Lian, Z. X., Zhang, W., Yoshida, K., Wakabayashi, K., Yang, G. X. et al., Biochemical and immunologic effects of rituximab in patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Hepatology 2012. 55: 512-521.
7. Juran, B. D., Hirschfield, G. M., Invernizzi, P., Atkinson, E. J., Li, Y., Xie, G., Kosoy, R. et al., Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants. Hum. Mol. Genet. 2012. 21: 5209-5221.
8. Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., Steinhart, A. H. et al., A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006. 314: 1461-1463.
9. Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P. et al., A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 2007. 445: 881-885.
10. Collins, F. S., Guyer, M. S. and Charkravarti, A., Variations on a theme: cataloging human DNA sequence variation. Science 1997. 278: 1580-1581.
11. Saunders, A. M., Strittmatter, W. J., Schmechel, D., George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L. et al., Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993. 43: 1467-1472.
12. Bertina, R. M., Koeleman, B. P., Koster, T., Rosendaal, F. R., Dirven, R. J., de Ronde, H., van der Velden, P. A. et al., Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994. 369: 64-67.
13. Dean, M., Carrington, M., Winkler, C., Huttley, G. A., Smith, M. W., Allikmets, R., Goedert, J. J. et al., Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and development study, multicenter AIDS cohort study, multicenter hemophilia cohort study, San Francisco city cohort, ALIVE study. Science 1996. 273: 1856-1862.
14. Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S. and Manolio, T. A., Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. U. S. A. 2009. 106: 9362-9367.
15. Wellcome Trust Case Control, C., Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 2007. 447: 661-678.
16. Omenetti, A., Popov, Y., Jung, Y., Choi, S. S., Witek, R. P., Yang, L., Brown, K. D. et al., The hedgehog pathway regulates remodelling responses to biliary obstruction in rats. Gut. 2008. 57: 1275-1282.
17. Omenetti, A., Syn, W. K., Jung, Y., Francis, H., Porrello, A., Witek, R. P., Choi, S. S. et al., Repair-related activation of hedgehog signaling promotes cholangiocyte chemokine production. Hepatology 2009. 50: 518-527.
18. Cooper, G. M., Johnson, J. A., Langaee, T. Y., Feng, H., Stanaway, I. B., Schwarz, U. I., Ritchie, M. D. et al., A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood 2008. 112: 1022-1027.
19. Hirschfield, G. M., Liu, X., Xu, C., Lu, Y., Xie, G., Lu, Y., Gu, X. et al., Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N. Engl. J. Med. 2009. 360: 2544-2555.
20. Liu, X., Invernizzi, P., Lu, Y., Kosoy, R., Lu, Y., Bianchi, I., Podda, M. et al., Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat. Genet. 2010. 42: 658-660.
21. Mells, G. F., Floyd, J. A., Morley, K. I., Cordell, H. J., Franklin, C. S., Shin, S. Y., Heneghan, M. A. et al., Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 2011. 43: 329-332.
22. Nakamura, M., Nishida, N., Kawashima, M., Aiba, Y., Tanaka, A., Yasunami, M., Nakamura, H. et al., Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population. Am. J. Hum. Genet. 2012. 91: 721-728.
23. Liu, J. Z., Almarri, M. A., Gaffney, D. J., Mells, G. F., Jostins, L., Cordell, H. J., Ducker, S. J. et al., Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 2012. 44: 1137-1141.
24. Invernizzi, P., Human leukocyte antigen in primary biliary cirrhosis: an old story now reviving. Hepatology 2011. 54: 714-723.
25. Kar, S. P., Seldin, M. F., Chen, W., Lu, E., Hirschfield, G. M., Invernizzi, P., Heathcote, J. et al., Pathway-based analysis of primary biliary cirrhosis genome-wide association studies. Genes Immun. 2013. 14: 179-186.
26. Ouyang, W., Oh, S. A., Ma, Q., Bivona, M. R., Zhu, J. and Li, M. O., TGF-beta cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor alpha expression. Immunity 2013. 39: 335-346.
27. McKay, F. C., Hoe, E., Parnell, G., Gatt, P., Schibeci, S. D., Stewart, G. J. and Booth, D. R., IL7Ralpha Expression and Upregulation by IFNbeta in Dendritic Cell Subsets Is Haplotype-Dependent. PLoS One 2013. 8: e77508.
28. Tarte, K., Zhan, F., De Vos, J., Klein, B. and Shaughnessy, J., Jr., Gene expression profiling of plasma cells and plasmablasts: toward a better understanding of the late stages of B-cell differentiation. Blood 2003. 102: 592-600.
29. Zhan, F., Tian, E., Bumm, K., Smith, R., Barlogie, B. and Shaughnessy, J., Jr., Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late-stage B-cell development. Blood 2003. 101: 1128-1140.
30. Shin, D. M., Lee, C. H. and Morse, H. C., 3rd, IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells. PLoS One 2011. 6: e27384.
31. Waight, J. D., Netherby, C., Hensen, M. L., Miller, A., Hu, Q., Liu, S., Bogner, P. N. et al., Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J. Clin. Invest. 2013. 123: 4464-4478.
32. Hirschfield, G. M., Liu, X., Han, Y., Gorlov, I. P., Lu, Y., Xu, C., Lu, Y. et al., Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat. Genet. 2010. 42: 655-657.
33. Liu, J. Z., Hov, J. R., Folseraas, T., Ellinghaus, E., Rushbrook, S. M., Doncheva, N. T., Andreassen, O. A. et al., Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat. Genet. 2013. 45: 670-675.
34. Poupon, R. E., Balkau, B., Eschwege, E. and Poupon, R., A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N. Engl. J. Med. 1991. 324: 1548-1554.
35. Poupon, R. E., Poupon, R. and Balkau, B., Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. N. Engl. J. Med. 1994. 330: 1342-1347.
36. Kuiper, E. M., Hansen, B. E., de Vries, R. A., den Ouden-Muller, J. W., van Ditzhuijsen, T. J., Haagsma, E. B., Houben, M. H. et al., Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology 2009. 136: 1281-1287.
37. Corpechot, C., Abenavoli, L., Rabahi, N., Chretien, Y., Andreani, T., Johanet, C., Chazouilleres, O. et al., Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 2008. 48: 871-877.
38. Pares, A., Caballeria, L. and Rodes, J., Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology 2006. 130: 715-720.
39. Carbone, M., Mells, G. F., Pells, G., Dawwas, M. F., Newton, J. L., Heneghan, M. A., Neuberger, J. M. et al., Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 2013. 144: 560-569 e567; quiz e513-564.
40. Fellay, J., Thompson, A. J., Ge, D., Gumbs, C. E., Urban, T. J., Shianna, K. V., Little, L. D. et al., ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 2010. 464: 405-408.
41. Koyasu, S., The role of PI3K in immune cells. Nat. Immunol. 2003. 4: 313-319.
42. Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J. Y., Sackler, R. S., Haynes, C., Henning, A. K. et al., Complement factor H polymorphism in age-related macular degeneration. Science 2005. 308: 385-389.
43. Rioux, J. D., Xavier, R. J., Taylor, K. D., Silverberg, M. S., Goyette, P., Huett, A., Green, T. et al., Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 2007. 39: 596-604.
44. Leonardi, C. L., Kimball, A. B., Papp, K. A., Yeilding, N., Guzzo, C., Wang, Y., Li, S. et al., Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008. 371: 1665-1674.
45. Mannon, P. J., Fuss, I. J., Mayer, L., Elson, C. O., Sandborn, W. J., Present, D., Dolin, B. et al., Anti-interleukin-12 antibody for active Crohn's disease. N. Engl. J. Med. 2004. 351: 2069-2079.
46. Burakoff, R., Barish, C. F., Riff, D., Pruitt, R., Chey, W. Y., Farraye, F. A., Shafran, I. et al., A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease. Inflamm. Bowel. Dis. 2006. 12: 558-565.
47. Braun, J., Davis, J., Dougados, M., Sieper, J., van der Linden, S., van der Heijde, D. and Group, A. W., First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann. Rheum. Dis. 2006. 65: 316-320.
48. Rutgeerts, P., Vermeire, S. and Van Assche, G., Biological therapies for inflammatory bowel diseases. Gastroenterology 2009. 136: 1182-1197.
49. Gisondi, P. and Girolomoni, G., Biologic therapies in psoriasis: a new therapeutic approach. Autoimmun. Rev. 2007. 6: 515-519.
50. Feldmann, M. and Maini, R. N., Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat. Med. 2003. 9: 1245-1250.
51. Tas, S. and Avci, O., Rapid clearance of psoriatic skin lesions induced by topical cyclopamine. A preliminary proof of concept study. Dermatology 2004. 209: 126-131.
52. Zhernakova, A., van Diemen, C. C. and Wijmenga, C., Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat. Rev. Genet. 2009. 10: 43-55.
53. Kita, H., Matsumura, S., He, X. S., Ansari, A. A., Lian, Z. X., Van de Water, J., Coppel, R. L. et al., Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis. J. Clin. Invest. 2002. 109: 1231-1240.
54. Becher, B., Durell, B. G. and Noelle, R. J., Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest. 2002. 110: 493-497.
55. Lleo, A., Gershwin, M. E., Mantovani, A. and Invernizzi, P., Towards common denominators in primary biliary cirrhosis: the role of IL-12. J. Hepatol. 2012. 56: 731-733.
56. Yoshida, K., Yang, G. X., Zhang, W., Tsuda, M., Tsuneyama, K., Moritoki, Y., Ansari, A. A. et al., Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor beta receptor type II mice. Hepatology 2009. 50: 1494-1500.
57. Li, Q. and Verma, I. M., NF-kappaB regulation in the immune system. Nat. Rev. Immunol. 2002. 2: 725-734.
58. Greenwald, R. J., Freeman, G. J. and Sharpe, A. H., The B7 family revisited. Annu. Rev. Immunol. 2005. 23: 515-548.
59. Scalapino, K. J. and Daikh, D. I., CTLA-4: a key regulatory point in the control of autoimmune disease. Immunol. Rev. 2008. 223: 143-155.
60. Dhirapong, A., Yang, G. X., Nadler, S., Zhang, W., Tsuneyama, K., Leung, P., Knechtle, S. et al., Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine model of primary biliary cirrhosis. Hepatology 2013. 57: 708-715.
61. Genovese, M. C., Becker, J. C., Schiff, M., Luggen, M., Sherrer, Y., Kremer, J., Birbara, C. et al., Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N. Engl. J. Med. 2005. 353: 1114-1123.
62. Kremer, J. M., Dougados, M., Emery, P., Durez, P., Sibilia, J., Shergy, W., Steinfeld, S. et al., Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005. 52: 2263-2271.
63. Abrams, J. R., Lebwohl, M. G., Guzzo, C. A., Jegasothy, B. V., Goldfarb, M. T., Goffe, B. S., Menter, A. et al., CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J. Clin. Invest. 1999. 103: 1243-1252.
64. Tacke, F., Luedde, T. and Trautwein, C., Inflammatory pathways in liver homeostasis and liver injury. Clin. Rev. Allergy Immunol. 2009. 36: 4-12.
65. Locksley, R. M., Killeen, N. and Lenardo, M. J., The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001. 104: 487-501.
66. Kitamura, K., Nakamoto, Y., Akiyama, M., Fujii, C., Kondo, T., Kobayashi, K., Kaneko, S. et al., Pathogenic roles of tumor necrosis factor receptor p55-mediated signals in dimethylnitrosamine-induced murine liver fibrosis. Lab. Invest. 2002. 82: 571-583.
67. Del Villar, K. and Miller, C. A., Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons. Proc. Natl. Acad. Sci. U. S. A. 2004. 101: 4210-4215.
68. Sleiman, P. M., Flory, J., Imielinski, M., Bradfield, J. P., Annaiah, K., Willis-Owen, S. A., Wang, K. et al., Variants of DENND1B associated with asthma in children. N. Engl. J. Med. 2010. 362: 36-44.
69. Sarma, V., Wolf, F. W., Marks, R. M., Shows, T. B. and Dixit, V. M., Cloning of a novel tumor necrosis factor-alpha-inducible primary response gene that is differentially expressed in development and capillary tube-like formation in vitro. J. Immunol. 1992. 148: 3302-3312.
70. Lleo, A., Bowlus, C. L., Yang, G. X., Invernizzi, P., Podda, M., Van de Water, J., Ansari, A. A. et al., Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis. Hepatology 2010. 52: 987-998.
71. Neuman, M., Angulo, P., Malkiewicz, I., Jorgensen, R., Shear, N., Dickson, E. R., Haber, J. et al., Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis. J. Gastroenterol. Hepatol. 2002. 17: 196-202.
72. Hochdorfer, T., Kuhny, M., Zorn, C. N., Hendriks, R. W., Vanhaesebroeck, B., Bohnacker, T., Krystal, G. et al., Activation of the PI3K pathway increases TLR-induced TNF-alpha and IL-6 but reduces IL-1beta production in mast cells. Cell Signal 2011. 23: 866-875.
73. Frey, R. S., Gao, X., Javaid, K., Siddiqui, S. S., Rahman, A. and Malik, A. B., Phosphatidylinositol 3-kinase gamma signaling through protein kinase Czeta induces NADPH oxidase-mediated oxidant generation and NF-kappaB activation in endothelial cells. J. Biol. Chem. 2006. 281: 16128-16138.
74. Varjosalo, M. and Taipale, J., Hedgehog: functions and mechanisms. Genes. Dev. 2008. 22: 2454-2472.
75. Ingham, P. W. and McMahon, A. P., Hedgehog signaling in animal development: paradigms and principles. Genes. Dev. 2001. 15: 3059-3087.
76. Bhardwaj, G., Murdoch, B., Wu, D., Baker, D. P., Williams, K. P., Chadwick, K., Ling, L. E. et al., Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat. Immunol. 2001. 2: 172-180.
77. Jung, Y., McCall, S. J., Li, Y. X. and Diehl, A. M., Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. Hepatology 2007. 45: 1091-1096.
78. Ge, D., Fellay, J., Thompson, A. J., Simon, J. S., Shianna, K. V., Urban, T. J., Heinzen, E. L. et al., Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009. 461: 399-401.
79. Suppiah, V., Moldovan, M., Ahlenstiel, G., Berg, T., Weltman, M., Abate, M. L., Bassendine, M. et al., IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat. Genet. 2009. 41: 1100-1104.
80. Tanaka, Y., Nishida, N., Sugiyama, M., Kurosaki, M., Matsuura, K., Sakamoto, N., Nakagawa, M. et al., Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat. Genet. 2009. 41: 1105-1109.
81. Shuldiner, A. R., O'Connell, J. R., Bliden, K. P., Gandhi, A., Ryan, K., Horenstein, R. B., Damcott, C. M. et al., Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009. 302: 849-857.
82. Takeuchi, F., McGinnis, R., Bourgeois, S., Barnes, C., Eriksson, N., Soranzo, N., Whittaker, P. et al., A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet. 2009. 5: e1000433.
83. Teichert, M., Eijgelsheim, M., Rivadeneira, F., Uitterlinden, A. G., van Schaik, R. H., Hofman, A., De Smet, P. A. et al., A genome-wide association study of acenocoumarol maintenance dosage. Hum. Mol. Genet. 2009. 18: 3758-3768.
84. Paumgartner, G. and Beuers, U., Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease. Clin. Liver. Dis. 2004. 8: 67-81, vi.
85. Kathiresan, S., Melander, O., Anevski, D., Guiducci, C., Burtt, N. P., Roos, C., Hirschhorn, J. N. et al., Polymorphisms associated with cholesterol and risk of cardiovascular events. N. Engl. J. Med. 2008. 358: 1240-1249.