Using GWAS to identify genetic predisposition in hepatic autoimmunity

Journal of Autoimmunity

Volumn 66, Issue , 2016, Pages 25-39

  Webb, G J ^a   Hirschfield, G M ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Autoimmune hepatitis; Biliary autoimmunity; Epigenetics; Epistasis; Genetic risk; Heritability; Immune regulation; Primary biliary cirrhosis; Primary sclerosing cholangitis

Indexed keywords

CD28 ANTIGEN; CHEMOKINE RECEPTOR CXCR5; FUCOSYLTRANSFERASE; GAMMA INTERFERON; INTERFERON; INTERFERON REGULATORY FACTOR 5; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ANTIBODY; INTERLEUKIN 23 RECEPTOR; INTERLEUKIN 7 RECEPTOR; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; STAT4 PROTEIN; GALACTOSIDE 2-ALPHA-L-FUCOSYLTRANSFERASE; HLA ANTIGEN; LNK PROTEIN, HUMAN; PROTEIN;

AUTOIMMUNE DISEASE; AUTOIMMUNE HEPATITIS; AUTOIMMUNE THYROIDITIS; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CELIAC DISEASE; DIABETES MELLITUS; EPISTASIS; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; HLA SYSTEM; HUMAN; NONHUMAN; PERNICIOUS ANEMIA; PHENOTYPE; PLEIOTROPY; PRIMARY BILIARY CIRRHOSIS; PRIMARY SCLEROSING CHOLANGITIS; PRIORITY JOURNAL; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SARCOIDOSIS; SCLERODERMA; SYSTEMIC LUPUS ERYTHEMATOSUS; THROMBOCYTOPENIC PURPURA; BILIARY CIRRHOSIS; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HAPLOTYPE; IMMUNOLOGY; LIVER; METABOLISM; RISK FACTOR; SCLEROSING CHOLANGITIS; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM;

ANTIGENS, CD28; AUTOIMMUNITY; CHOLANGITIS, SCLEROSING; EPISTASIS, GENETIC; FUCOSYLTRANSFERASES; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HAPLOTYPES; HEPATITIS, AUTOIMMUNE; HLA ANTIGENS; HUMANS; INTERLEUKIN-12; INTERLEUKIN-2; LIVER; LIVER CIRRHOSIS, BILIARY; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS; RISK FACTORS; SIGNAL TRANSDUCTION; STAT4 TRANSCRIPTION FACTOR;

EID: 84953209650     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2015.08.016     Document Type: Review

References (148)

1. Davidson A., Diamond B. Autoimmune diseases. N. Engl. J. Med. 2001, 345:340-350.
2. Lleo A., Invernizzi P., Gao B., Podda M., Gershwin M.E. Definition of human autoimmunity - autoantibodies versus autoimmune disease. Autoimmun. Rev. 2010, 9:A259-A266.
3. Cooper G.S., Bynum M.L.K., Somers E.C. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J. Autoimmun. 2009, 33:197-207.
4. Somers E.C., Thomas S.L., Smeeth L., Hall A.J. Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder?. Am. J. Epidemiol. 2009, 169:749-755.
5. Hirschfield G.M., Gershwin M.E. The immunobiology and Pathophysiology of Primary Biliary Cirrhosis. Annu. Rev. Pathol. Mech. Dis. 2013, 8:303-330.
6. Corrigan M., Hirschfield G.M., Oo Y.H., Adams D.H. Autoimmune hepatitis: an approach to disease understanding and management. Br. Med. Bull. 2015, 114:181-191.
7. Hirschfield G.M., Karlsen T.H., Lindor K.D., Adams D.H. Primary sclerosing cholangitis. Lancet 2013, 382:1587-1599.
8. Boonstra K., Beuers U., Ponsioen C.Y. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: A systematic review. J. Hepatol. 2012, 56:1181-1188.
9. Gronbaek L., Vilstrup H., Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J. Hepatol. 2014, 60:612-617.
10. Marson A., Housley W.J., Hafler D.A. Genetic basis of autoimmunity. J. Clin. Invest. 2015, 125:2234-2241.
11. McCarthy M.I., Abecasis G.R., Cardon L.R., Goldstein D.B., Little J., Ioannidis J.P., et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat. Rev. Genet. 2008, 9:356-369.
12. Selmi C., Mayo M.J., Bach N., Ishibashi H., Invernizzi P., Gish R.G., et al. Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment. YGAST 2004, 127:485-492.
13. van Gerven N.M., Verwer B.J., Witte B.I., van Erpecum K.J., van Buuren H.R., Maijers I., et al. Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands. Scand. J. Gastroenterol. 2014, 49:1245-1254.
14. Jones D.E., Watt F.E., Metcalf J.V., Bassendine M.F., James O.F. Familial primary biliary cirrhosis reassessed: a geographically-based population study. J. Hepatol. 1999, 30:402-407.
15. Gershwin M.E., Selmi C., Worman H.J., Gold E.B., Watnik M., Utts J., et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology 2005, 42:1194-1202.
16. Bergquist A., Montgomery S.M., Bahmanyar S., Olsson R., Danielsson A., Lindgren S., et al. Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis. Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2008, 6:939-943.
17. Smyk D.S., Bogdanos D.P., Rigopoulou E.I. Risk Factors for Autoimmune Hepatitis: From Genes and Pregnancy to Vaccinations and Pollutants. Immunogastroenterology 2013, 2:29-37.
18. Lazaridis K.N., Juran B.D., Boe G.M., Slusser J.P., de Andrade M., Homburger H.A., et al. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology 2007, 46:785-792.
19. Mantaka A., Koulentaki M., Chlouverakis G., Enele-Melono J.M., Darivianaki A., Tzardi M., et al. Primary biliary cirrhosis in a genetically homogeneous population: Disease associations and familial occurrence rates. BMC Gastroenterol. 2012, 12:1.
20. Selmi C., Invernizzi P., Zuin M., Podda M., Seldin M.F., Gershwin M.E. Genes and (auto)immunity in primary biliary cirrhosis. Genes Immun. 2005, 6:543-556.
21. Arbour L., Rupps R., Field L., Ross P., Erikson A., Henderson H., et al. Characteristics of primary biliary cirrhosis in British Columbia's first nations population. Can. J. Gastroenterol. 2005, 19:305-310.
22. Delgado J., Sperber A.D., Novack V., Delgado B., Edelman L., Gaspar N., et al. The epidemiology of primary biliary cirrhosis in southern Israel. Israel Med. Assoc. J. 2005, 7:717-721.
23. Tsuji K., Watanabe Y., Van de Water J., Nakanishi T., Kajiyama G., Parikh-Patel A., et al. Familial primary biliary cirrhosis in Hiroshima. J. Autoimmun. 1999, 13:171-178.
24. Lohse A.W., Mieli-Vergani G. Autoimmune hepatitis. J. Hepatol. 2011, 55:171-182.
25. Bussone G., Mouthon L. Autoimmune manifestations in primary immune deficiencies. Autoimmun. Rev. 2009, 8:332-336.
26. Schubert D., Bode C., Kenefeck R., Hou T.Z., Wing J.B., Kennedy A., et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat. Med. 2014, 1-9.
27. Barzaghi F., Passerini L., Bacchetta R. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front. Immunol. 2012 Jul 31, 3:211. 10.3389/fimmu.2012.00211.
28. Webb G., Richter A., Blahova M., Curbishley S., Li K.-K., Neil D., et al. P1196: Autoimmune hepatitis with T-regulatory cell deficiency in the context of GATA-2 dysfunction: a novel single gene association. J. Hepatol. 2015, 62:S804.
29. Boonstra K., de Vries E.M., van Geloven N., van Erpecum K.J., Spanier M., Poen A.C., et al. Risk factors for primary sclerosing cholangitis. Liver Int. Off. J. Int. Assoc. Study Liver Published online 28 Aug 2015, 10.1111/liv.12894.
30. Mitchell K.J. What is complex about complex disorders?. Genome Biol. 2012, 13:237.
31. Karlsen T.H., Schrumpf E., Boberg K.M. Genetic epidemiology of primary sclerosing cholangitis. World J. Gastroenterol. 2007, 13:5421-5431.
32. Czaja A.J. Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitis. Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2008, 6:379-388.
33. Invernizzi P., Selmi C., Mackay I.R., Podda M., Gershwin M.E. From bases to basis: linking genetics to causation in primary biliary cirrhosis. Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2005, 3:401-410.
34. Visscher P.M., Brown M.A., McCarthy M.I., Yang J. Five years of GWAS discovery. Am. J. Hum. Genet. 2012, 90:7-24.
35. Sanseau P., Agarwal P., Barnes M.R., Pastinen T., Richards J.B., Cardon L.R., et al. Use of genome-wide association studies for drug repositioning. Nat. Biotechnol. 2012, 30:317-320.
36. de Boer Y.S., van Gerven N.M., Zwiers A., Verwer B.J., van Hoek B., van Erpecum K.J., et al. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1. Gastroenterology 2014, 147. 443-52 e5.
37. Parkes M., Cortes A., van Heel D.A., Brown M.A. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat. Rev. Genet. 2013, 14:661-673.
38. Lessard C.J., Ice J.A., Adrianto I., Wiley G.B., Kelly J.A., Gaffney P.M., et al. The genomics of autoimmune disease in the era of genome-wide association studies and beyond. Autoimmun. Rev. 2012, 11:267-275.
39. Nakamura M., Nishida N., Kawashima M., Aiba Y., Tanaka A., Yasunami M., 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.
40. Dong M., Li J., Tang R., Zhu P., Qiu F., Wang C., et al. Multiple genetic variants associated with primary biliary cirrhosis in a Han Chinese population. Clin. Rev. Allergy Immunol. 2015 Jun, 48(2-3):316-321. 10.1007/s12016-015-8472-0.
41. Illing P.T., Vivian J.P., Dudek N.L., Kostenko L., Chen Z., Bharadwaj M., et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 2012, 486:554-558.
42. Invernizzi P., Ransom M., Raychaudhuri S., Kosoy R., Lleo A., Shigeta R., et al. Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis. Genes Immun. 2012, 13:461-468.
43. Braley-Mullen H., Sharp G.C., Medling B., Tang H. Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. J. Autoimmun. 1999, 12:157-165.
44. Raychaudhuri S., Sandor C., Stahl E.A., Freudenberg J., Lee H.S., Jia X., et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 2012, 44:291-296.
45. Wakabayashi K., Lian Z.X., Moritoki Y., Lan R.Y., Tsuneyama K., Chuang Y.H., et al. IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. Hepatology 2006, 44:1240-1249.
46. Aoki C.A., Roifman C.M., Lian Z.-X., Bowlus C.L., Norman G.L., Shoenfeld Y., et al. IL-2 receptor alpha deficiency and features of primary biliary cirrhosis. J. Autoimmun. 2006, 2012:50-53.
47. Bouillet P., Metcalf D., Huang D.C., Tarlinton D.M., Kay T.W., Kontgen F., et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 1999, 286:1735-1738.
48. Sugawara I., Yamada H., Mizuno S. Relative importance of STAT4 in murine tuberculosis. J. Med. Microbiol. 2003, 52:29-34.
49. Picard C., Fieschi C., Altare F., Al-Jumaah S., Al-Hajjar S., Feinberg J., et al. Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am. J. Hum. Genet. 2002, 70:336-348.
50. Yang Z., Chen M., Ellett J.D., Fialkow L.B., Carter J.D., McDuffie M., et al. Autoimmune diabetes is blocked in Stat4-deficient mice. J. Autoimmun. 2004, 22:191-200.
51. Yao Y., Yang W., Yang Y.-Q., Ma H.-D., Lu F.-T., Li L., et al. Distinct from its canonical effects, deletion of IL-12p40 induces cholangitis and fibrosis in interleukin-2Rα-/- mice. J. Autoimmun. 2014, 51:99-108.
52. Yoshida K., Yang G.-X., Zhang W., Tsuda M., Tsuneyama K., Moritoki Y., et al. Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor β receptor type II mice. Hepatology 2009, 50:1494-1500.
53. Tsuda M., Zhang W., Yang G.X., Tsuneyama K., Ando Y., Kawata K., et al. Deletion of interleukin (IL)-12p35 induces liver fibrosis in dominant-negative TGFbeta receptor type II mice. Hepatology 2013, 57:806-816.
54. Rausch P., Rehman A., Kunzel S., Hasler R., Ott S.J., Schreiber S., et al. Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:19030-19035.
55. Tong M., McHardy I., Ruegger P., Goudarzi M., Kashyap P.C., Haritunians T., et al. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism. ISME J. 2014, 8:2193-2206.
56. Katayama H., Mori T., Seki Y., Anraku M., Iseki M., Ikutani M., et al. Lnk prevents inflammatory CD8(+) T-cell proliferation and contributes to intestinal homeostasis. Eur. J. Immunol. 2014, 44:1622-1632.
57. Zhernakova A., Elbers C.C., Ferwerda B., Romanos J., Trynka G., Dubois P.C., et al. Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. Am. J. Hum. Genet. 2010, 86:970-977.
58. Juran B.D., Hirschfield G.M., Invernizzi P., Atkinson E.J., Li Y., Xie G., 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.
59. Juran B.D., Atkinson E.J., Larson J.J., Schlicht E.M., Liu X., Heathcote E.J., et al. Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T-lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: evidence for a gene-gene interaction. Hepatology 2010, 52:223-229.
60. Kopp T., Riedl E., Bangert C., Bowman E.P., Greisenegger E., Horowitz A., et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature 2015, 521:222-226.
61. Ge D., Fellay J., Thompson A.J., Simon J.S., Shianna K.V., Urban T.J., et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009, 461:399-401.
62. van Gerven N.M.F., de Boer Y.S., Zwiers A., Verwer B.J., Drenth J.P.H., van Hoek B., et al. HLA-DRB1[ast]03:01 and HLA-DRB1[ast]04:01 modify the presentation and outcome in autoimmune hepatitis type-1. Genes Immun. 2015, 16:247-252.
63. Nakamura M., Yasunami M., Kondo H., Horie H., Aiba Y., Komori A., et al. Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): the HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC. Hepatol. Res. Off. J. Jpn. Soc. Hepatol. 2010, 40:494-504.
64. Zhao D.T., Liao H.Y., Zhang X., Liu Y.M., Zhao Y., Zhang H.P., et al. Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis. Liver Int. Off. J. Int. Assoc. Study Liver 2014, 34:220-226.
65. Karlsen T.H., Boberg K.M., Vatn M., Bergquist A., Hampe J., Schrumpf E., et al. Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis. Genes Immun. 2007, 8:275-278.
66. Fosby B., Naess S., Hov J.R., Traherne J., Boberg K.M., Trowsdale J., et al. HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation. World J. Gastroenterol. 2014, 20:3986-4000.
67. Czaja A.J., Carpenter H.A., Moore S.B. Clinical and HLA phenotypes of type 1 autoimmune hepatitis in North American patients outside DR3 and DR4. Liver Int. Off. J. Int. Assoc. Study Liver 2006, 26:552-558.
68. Montano-Loza A.J., Carpenter H.A., Czaja A.J. Clinical significance of HLA DRB103-DRB104 in type 1 autoimmune hepatitis. Liver Int. Off. J. Int. Assoc. Study Liver 2006, 26:1201-1208.
69. Umemura T., Joshita S., Ichijo T., Yoshizawa K., Katsuyama Y., Tanaka E., et al. Human leukocyte antigen class II molecules confer both susceptibility and progression in Japanese patients with primary biliary cirrhosis. Hepatology 2012, 55:506-511.
70. Chow I.T., James E.A., Gates T.J., Tan V., Moustakas A.K., Papadopoulos G.K., et al. Differential binding of pyruvate dehydrogenase complex-E2 epitopes by DRB1*08:01 and DRB1*11:01 Is predicted by their structural motifs and correlates with disease risk. J. Immunol. 2013, 190:4516-4524.
71. Chapman R., Fevery J., Kalloo A., Nagorney D.M., Boberg K.M., Shneider B., et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010, 51:660-678.
72. Sebode M., Peiseler M., Franke B., Schwinge D., Schoknecht T., Wortmann F., et al. Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms. J. Hepatol. 2014, 60:1010-1016.
73. Liaskou E., Jeffery L.E., Trivedi P.J., Reynolds G.M., Suresh S., Bruns T., et al. Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis. Gastroenterology 2014, 147. 221-32 e7.
74. Pawlik A., Ostanek L., Brzosko I., Brzosko M., Masiuk M., Machalinski B., et al. The expansion of CD4+CD28- T cells in patients with rheumatoid arthritis. Arthritis Res. Ther. 2003, 5:R210-R213.
75. Aiba Y., Nakamura M., Joshita S., Inamine T., Komori A., Yoshizawa K., et al. Genetic polymorphisms in CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliary cirrhosis in Japanese patients. J. Gastroenterol. 2011, 46:1203-1212.
76. Hitomi Y., Kawashima M., Aiba Y., Nishida N., Matsuhashi M., Okazaki H., et al. Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1. Hum. Genet. 2015 Jul, 134(7):737-747. 10.1007/s00439-015-1556-3.
77. Webb G.J., Hirschfield G.M. Follicles, germinal centers, and immune mechanisms in primary biliary cirrhosis. Hepatology 2015, 61:424-427.
78. Wang L., Sun Y., Zhang Z., Jia Y., Zou Z., Ding J., et al. CXCR5+ CD4+ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis. Hepatology 2015 Feb, 61(2):627-638. 10.1002/hep.27306.
79. Kikuchi K., Tsuneyama K., Yamada H., Kajiyama Y., Matsumoto K., Tsunashima H., et al. Splenic lymph follicles generate immunoglobulin M-producing B cells in primary biliary cirrhosis. Hepatol. Res. 2014 Oct, 44(10):E253-E256. 10.1111/hepr.12231.
80. Carbone M., Mells G.F., Alexander G.J., Westbrook R.H., Heneghan M.A., Sandford R.N., et al. Calcineurin inhibitors and the IL12A locus influence risk of recurrent primary biliary cirrhosis after liver transplantation. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2013, 13:1110-1111.
81. Hirschfield G., Gershwin M., Strauss R., Mayo M., Levy C., Zou B., et al. P367 phase 2 study evaluating the efficacy and safety of Ustekinumab in patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid. J. Hepatol. 2014, 1:S189-S190.
82. Tang R., Chen H., Miao Q., Bian Z., Ma W., Feng X., et al. The Cumulative Effects of Known Susceptibility Variants to Predict Primary Biliary Cirrhosis Risk 2015, 1-6.
83. Manolio T.A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A., Hunter D.J., et al. Finding the missing heritability of complex diseases. Nature 2009, 461:747-753.
84. Okada Y., Wu D., Trynka G., Raj T., Terao C., Ikari K., et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014, 506:376-381.
85. Karlsen T.H., Lammert F., Thompson R.J. Genetics of liver disease: from pathophysiology to clinical practice. J. Hepatol. 2015, 62:S6-S14.
86. Bowlus C.L., Li C.S., Karlsen T.H., Lie B.A., Selmi C. Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations. Liver Transplant. Off. Publ. Am. Assoc. Study Liver Dis. Int. Liver Transplant. Soc. 2010, 16:1324-1330.
87. Cortes A., Brown M.A. Promise and pitfalls of the immunochip. Arthritis Res. Ther. 2011, 13:101.
88. Karlsson E.K., Kwiatkowski D.P., Sabeti P.C. Natural selection and infectious disease in human populations. Nat. Rev. Genet. 2014, 15:379-393.
89. Jostins L., Ripke S., Weersma R.K., Duerr R.H., McGovern D.P., Hui K.Y., et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012, 491:119-124.
90. Farh K.K.-H., Marson A., Zhu J., Kleinewietfeld M., Housley W.J., Beik S., et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2015, 518:337-343.
91. Invernizzi P., Miozzo M., Battezzati P.M., Bianchi I., Grati F.R., Simoni G., et al. Frequency of monosomy X in women with primary biliary cirrhosis. Lancet 2004, 363:533-535.
92. Invernizzi P., Miozzo M., Selmi C., Persani L., Battezzati P.M., Zuin M., et al. X chromosome monosomy: a common mechanism for autoimmune diseases. J. Immunol. 2005, 175:575-578.
93. Lleo A., Liao J., Invernizzi P., Zhao M., Bernuzzi F., Ma L., et al. Immunoglobulin M levels inversely correlate with CD40 ligand promoter methylation in patients with primary biliary cirrhosis. Hepatology 2012, 55:153-160.
94. Lleo A., Zhang W., Zhao M., Tan Y., Bernuzzi F., Zhu B., et al. DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis. Clin. Epigenetics 2015, 7:61.
95. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature 2015, 523:588-591. Consortium C.
96. Liu J.Z., Almarri M.A., Gaffney D.J., Mells G.F., Jostins L., Cordell H.J., et al. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat. Publ. Group 2012, 44:1137-1141.
97. Liu J.Z., Hov J.R., Folseraas T., Ellinghaus E., Rushbrook S.M., Doncheva N.T., et al. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat. Genet. 2013, 45:670-675.
98. Cordell H.J., Han Y., Li Y., Mells G.F., Hirschfield G.M. International genome-wide meta-analysis in primary biliary cirrhosis discovers six new risk loci and highlights the role of JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways in disease etiology. Nat. Commun. 2015, 1-13. [in press].
99. Gershwin M.E., Shoenfeld Y. Abul Abbas: an epitome of scholarship. J. Autoimmun. 2013, 45:1-6.
100. Steinman L., Shoenfeld Y. From defining antigens to new therapies in multiple sclerosis: honoring the contributions of Ruth Arnon and Michael Sela. J. Autoimmun. 2014, 54:1-7.
101. Krzywinski M., Schein J., Birol I., Connors J., Gascoyne R., Horsman D., et al. Circos: an information aesthetic for comparative genomics. Genome Res. 2009, 19:1639-1645.
102. Yu T.K., Caudell E.G., Smid C., Grimm E.A. IL-2 activation of NK cells: involvement of MKK1/2/ERK but not p38 kinase pathway. J. Immunol. 2000, 164:6244-6251.
103. Mingari M.C., Gerosa F., Carra G., Accolla R.S., Moretta A., Zubler R.H., et al. Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells. Nature 1984, 312:641-643.
104. Malek T.R. The biology of interleukin-2. Annu. Rev. Immunol. 2008, 26:453-479.
105. Nelson B.H. IL-2, regulatory T cells, and tolerance. J. Immunol. 2004, 172:3983-3988.
106. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 2003, 3:133-146.
107. Croxford A.L., Kulig P., Becher B. IL-12-and IL-23 in health and disease. Cytokine Growth Factor Rev. 2014, 25:415-421.
108. Watt F.E., James O.F.W., Jones D.E.J. Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study. QJM 2004, 97:397-406.
109. Lamberts L.E., Janse M., Haagsma E.B., van den Berg A.P., Weersma R.K. Immune-mediated diseases in primary sclerosing cholangitis. Dig. Liver Dis. Off. J. Italian Soc. Gastroenterol. Italian Assoc. Study Liver 2011, 43:802-806.
110. Werner M., Prytz H., Ohlsson B., Almer S., Bjornsson E., Bergquist A., et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand. J. Gastroenterol. 2008, 43:1232-1240.
111. Hirschfield G.M., Liu X., Xu C., Lu Y., Xie G., Lu Y., et al. Primary biliary cirrhosis associated with HLA, IL12A,and IL12RB2 variants. N. Engl. J. Med. 2009, 360:2544-2555.
112. Hirschfield G.M., Liu X., Han Y., Gorlov I.P., Lu Y., Xu C., et al. Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat. Publ. Group 2010, 42:655-657.
113. Liu X., Pietro I., Lu Y., Kosoy R., Lu Y., Bianchi I., et al. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat. Publ. Group 2010, 42:658-660.
114. Mells G.F., Floyd J.A.B., Morley K.I., Cordell H.J., Franklin C.S., Shin S.-Y., et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 2011, 43:329-332.
115. Liu X., Invernizzi P., Lu Y., Kosoy R., Lu Y., Bianchi I., et al. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat. Publ. Group 2010, 42:658-660.
116. Karlsen T.H., Franke A., Melum E., Kaser A., Hov J.R., Balschun T., et al. Genome-wide association analysis in primary sclerosing cholangitis. Gastroenterology 2010, 138:1102-1111.
117. Melum E., Franke A., Schramm C., Weismüller T.J., Gotthardt D.N., Offner F.A., et al. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nat. Publ. Group 2010, 43:17-19.
118. Folseraas T., Melum E., Rausch P., Juran B.D., Ellinghaus E., Shiryaev A., et al. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J. Hepatol. 2012, 57:366-375.
119. Srivastava B., Mells G.F., Cordell H.J., Muriithi A., Brown M., Ellinghaus E., et al. Fine mapping and replication of genetic risk loci in primary sclerosing cholangitis. Scand. J. Gastroenterol. 2012, 47:820-826.
120. Ellinghaus D., Folseraas T., Holm K., Ellinghaus E., Melum E., Balschun T., et al. Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4. Hepatology 2013, 58:1074-1083.
121. Donaldson P.T., Farrant J.M., Wilkinson M.L., Hayllar K., Portmann B.C., Williams R. Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis. Hepatology 1991, 13:129-133.
122. Donaldson P.T. Genetics of liver disease: immunogenetics and disease pathogenesis. Gut 2004, 53:599-608.
123. Strettell M.D., Donaldson P.T., Thomson L.J., Santrach P.J., Moore S.B., Czaja A.J., et al. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology 1997, 112:2028-2035.
124. Yoshizawa K., Ota M., Katsuyama Y., Ichijo T., Matsumoto A., Tanaka E., et al. Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis. J. Hepatol. 2005, 42:578-584.
125. Bittencourt P.L., Goldberg A.C., Cancado E.L., Porta G., Carrilho F.J., Farias A.Q., et al. Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2. Am. J. Gastroenterol. 1999, 94:1906-1913.
126. Amarapurkar D.N., Patel N.D., Amarapurkar A.D., Kankonkar S.R. HLA genotyping in type-I autoimmune hepatitis in Western India. J. Assoc. Phys. India 2003, 51:967-969.
127. Lott J.M., Sumpter T.L., Turnquist H.R. New dog and new tricks: evolving roles for IL-33 in type 2 immunity. J. Leukoc. Biol. 2015, 97:1037-1048.
128. Luo S., Rubinsztein D.C. BCL2L11/BIM. Autophagy 2012, 9:104-105.
129. Rudd C.E., Taylor A., Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev. 2009, 229:12-26.
130. Hieshima K., Imai T., Opdenakker G., Van Damme J., Kusuda J., Tei H., et al. Molecular cloning of a novel human CC chemokine liver and activation-regulated chemokine (LARC) expressed in liver. Chemotactic activity for lymphocytes and gene localization on chromosome 2. J. Biol. Chem. 1997, 272:5846-5853.
131. Maravillas-Montero J.L., Burkhardt A.M., Hevezi P.A., Carnevale C.D., Smit M.J., Zlotnik A. Cutting edge: GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17. J. Immunol. 2015, 194:29-33.
132. Song H., Mak K.K., Topol L., Yun K., Hu J., Garrett L., et al. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:1431-1436.
133. Hayden M.S., Ghosh S. NF-kappaB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 2012, 26:203-234.
134. Strebovsky J., Walker P., Lang R., Dalpke A.H. Suppressor of cytokine signaling 1 (SOCS1) limits NFkappaB signaling by decreasing p65 stability within the cell nucleus. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2011, 25:863-874.
135. Muto A., Tashiro S., Nakajima O., Hoshino H., Takahashi S., Sakoda E., et al. The transcriptional programme of antibody class switching involves the repressor Bach2. Nature 2004, 429:566-571.
136. Roychoudhuri R., Hirahara K., Mousavi K., Clever D., Klebanoff C.A., Bonelli M., et al. BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis. Nature 2013, 498:506-510.
137. Vereecke L., Beyaert R., van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 2009, 30:383-391.
138. Schubart D.B., Rolink A., Kosco-Vilbois M.H., Botteri F., Matthias P. B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation. Nature 1996, 383:538-542.
139. Sanosaka M., Fujimoto M., Ohkawara T., Nagatake T., Itoh Y., Kagawa M., et al. Salt-inducible kinase 3 deficiency exacerbates lipopolysaccharide-induced endotoxin shock accompanied by increased levels of pro-inflammatory molecules in mice. Immunology 2015, 145:268-278.
140. Kumpfel T., Hohlfeld R. Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis. Nat. Rev. Neurol. 2009, 5:528-529.
141. Barneda-Zahonero B., Roman-Gonzalez L., Collazo O., Rafati H., Islam A.B., Bussmann L.H., et al. HDAC7 is a repressor of myeloid genes whose downregulation is required for transdifferentiation of pre-B cells into macrophages. PLoS Genet. 2013, 9:e1003503.
142. Devalliere J., Charreau B. The adaptor Lnk (SH2B3): an emerging regulator in vascular cells and a link between immune and inflammatory signaling. Biochem. Pharmacol. 2011, 82:1391-1402.
143. Green E.A., Flavell R.A. TRANCE-RANK, a new signal pathway involved in lymphocyte development and T cell activation. J. Exp. Med. 1999, 189:1017-1020.
144. Sun J., Matthias G., Mihatsch M.J., Georgopoulos K., Matthias P. Lack of the transcriptional coactivator OBF-1 prevents the development of systemic lupus erythematosus-like phenotypes in aiolos mutant mice. J. Immunol. 2003, 170:1699-1706.
145. Forrest M.P., Hill M.J., Quantock A.J., Martin-Rendon E., Blake D.J. The emerging roles of TCF4 in disease and development. Trends Mol. Med. 2014, 20:322-331.
146. Martinet L., Smyth M.J. Balancing natural killer cell activation through paired receptors. Nat. Rev. Immunol. 2015, 15:243-254.
147. Ishizaki M., Akimoto T., Muromoto R., Yokoyama M., Ohshiro Y., Sekine Y., et al. Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. J. Immunol. 2011, 187:181-189.
148. Sasaki K., Hamazaki J., Koike M., Hirano Y., Komatsu M., Uchiyama Y., et al. PAC1 gene knockout reveals an essential role of chaperone-mediated 20S proteasome biogenesis and latent 20S proteasomes in cellular homeostasis. Mol. Cell. Biol. 2010, 30:3864-3874.