The putative role of endoplasmic reticulum aminopeptidases in autoimmunity: Insights from genomic-wide association studies

Autoimmunity Reviews

Volumn 12, Issue 2, 2012, Pages 281-288

  Fierabracci, Alessandra ^a   Milillo, Annamaria ^a   Locatelli, Franco ^a,b   Fruci, Doriana ^a  

^a BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

Author keywords

Antigen processing; Autoimmunity etiopathogenesis; ERAPs; GWAS; MHC class I

Indexed keywords

AMINOPEPTIDASE; CYTOKINE RECEPTOR; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 2; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; UNCLASSIFIED DRUG;

ANKYLOSING SPONDYLITIS; ANTIGEN PRESENTATION; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CROHN DISEASE; ENDOPLASMIC RETICULUM; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; MULTIPLE SCLEROSIS; PROTEIN FUNCTION; PROTEIN STRUCTURE; PSORIASIS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

AMINOPEPTIDASES; ANIMALS; AUTOIMMUNE DISEASES; AUTOIMMUNITY; ENDOPLASMIC RETICULUM; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS;

EID: 84870255603     PISSN: 15689972     EISSN: 18730183     Source Type: Journal    
DOI: 10.1016/j.autrev.2012.04.007     Document Type: Review

References (92)

1. Fierabracci A., Ayroldi E. Experimental strategies in autoimmunity: antagonists of cytokines and their receptors, nanocarriers, inhibitors of immunoproteasome, leukocyte migration and protein kinases. Curr Pharm Des 2011, 17:3094-3107.
2. Shapira Y., Agmon-Levin N., Shoenfeld Y. Defining and analyzing geoepidemiology and human autoimmunity. J Autoimmun 2010, 34:J168-J177.
3. van Belle T.L., Coppieters K.T., von Herrath M.G. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 2011, 91:79-118.
4. Sestak A.L., Furnrohr B.G., Harley J.B., Merrill J.T., Namjou B. The genetics of systemic lupus erythematosus and implications for targeted therapy. Ann Rheum Dis 2011, 70(Suppl. 1):i37-i43.
5. Agmon-Levin N., Mosca M., Petri M., Shoenfeld Y. Systemic lupus erythematosus one disease or many?. Autoimmun Rev 2011, 10.1016/j.autrev.2011.10.020.
6. Hoppenbrouwers I.A., Hintzen R.Q. Genetics of multiple sclerosis. Biochim Biophys Acta 2011, 1812:194-201.
7. Kaser A., Zeissig S., Blumberg R.S. Genes and environment: how will our concepts on the pathophysiology of IBD develop in the future?. Dig Dis 2010, 28:395-405.
8. Delgado-Vega A., Sanchez E., Lofgren S., Castillejo-Lopez C., Alarcon-Riquelme M.E. Recent findings on genetics of systemic autoimmune diseases. Curr Opin Immunol 2010, 22:698-705.
9. Nestle F.O., Kaplan D.H., Barker J. Psoriasis. N Engl J Med 2009, 361:496-509.
10. Anderson M.S., Su M.A. Aire and T cell development. Curr Opin Immunol 2011, 23:198-206.
11. Fierabracci A. Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity. Autoimmun Rev 2011, 10:137-143.
12. Chang H.D., Radbruch A. Targeting pathogenic T helper cell memory. Ann Rheum Dis 2011, 70(Suppl. 1):i85-i87.
13. Nagafuchi S. The role of B cells in regulating the magnitude of immune response. Microbiol Immunol 2010, 54:487-490.
14. Hu Y., Shen F., Crellin N.K., Ouyang W. The IL-17 pathway as a major therapeutic target in autoimmune diseases. Ann N Y Acad Sci 2011, 1217:60-76.
15. Lee J.H., Noh J., Noh G., Choi W.S., Cho S., Lee S.S. Allergen-specific transforming growth factor-beta-producing CD19+CD5+ regulatory B-cell (Br3) responses in human late eczematous allergic reactions to cow's milk. J Interferon Cytokine Res 2011, 31:441-449.
16. Yokosuka T., Saito T. The immunological synapse, TCR microclusters, and T cell activation. Curr Top Microbiol Immunol 2010, 340:81-107.
17. Yang J., Reth M. The dissociation activation model of B cell antigen receptor triggering. FEBS Lett 2010, 584:4872-4877.
18. Gregersen P.K. Closing the gap between genotype and phenotype. Nat Genet 2009, 41:958-959.
19. Dittmar M., Kahaly G.J. Genetics of the autoimmune polyglandular syndrome type 3 variant. Thyroid 2010, 20:737-743.
20. Neefjes J., Jongsma M.L., Paul P., Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 2011, 11:823-836.
21. Saveanu L., Carroll O., Lindo V., Del Val M., Lopez D., Lepelletier Y., et al. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol 2005, 6:689-697.
22. Hughes A.L., Yeager M. Natural selection at major histocompatibility complex loci of vertebrates. Annu Rev Genet 1998, 32:415-435.
23. Laustsen P.G., Vang S., Kristensen T. Mutational analysis of the active site of human insulin-regulated aminopeptidase. Eur J Biochem 2001, 268:98-104.
24. Tsujimoto M., Hattori A. The oxytocinase subfamily of M1 aminopeptidases. Biochim Biophys Acta 2005, 1751:9-18.
25. Andres A.M., Dennis M.Y., Kretzschmar W.W., Cannons J.L., Lee-Lin S.Q., Hurle B., et al. Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS Genet 2010, 6:e1001157.
26. Forloni M., Albini S., Limongi M.Z., Cifaldi L., Boldrini R., Nicotra M.R., et al. NF-kappaB, and not MYCN, regulates MHC class I and endoplasmic reticulum aminopeptidases in human neuroblastoma cells. Cancer Res 2010, 70:916-924.
27. Cui X., Hawari F., Alsaaty S., Lawrence M., Combs C.A., Geng W., et al. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest 2002, 110:515-526.
28. Cui X., Rouhani F.N., Hawari F., Levine S.J. Shedding of the type II IL-1 decoy receptor requires a multifunctional aminopeptidase, aminopeptidase regulator of TNF receptor type 1 shedding. J Immunol 2003, 171:6814-6819.
29. Cui X., Rouhani F.N., Hawari F., Levine S.J. An aminopeptidase, ARTS-1, is required for interleukin-6 receptor shedding. J Biol Chem 2003, 278:28677-28685.
30. Yamamoto N., Nakayama J., Yamakawa-Kobayashi K., Hamaguchi H., Miyazaki R., Arinami T. Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension. Hum Mutat 2002, 19:251-257.
31. Watanabe Y., Shibata K., Kikkawa F., Kajiyama H., Ino K., Hattori A., et al. Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system. Clin Cancer Res 2003, 9:6497-6503.
32. Hattori A., Matsumoto K., Mizutani S., Tsujimoto M. Genomic organization of the human adipocyte-derived leucine aminopeptidase gene and its relationship to the placental leucine aminopeptidase/oxytocinase gene. J Biochem 2001, 130:235-241.
33. Kim S., Lee S., Shin J., Kim Y., Evnouchidou I., Kim D., et al. Human cytomegalovirus microRNA miR-US4-1 inhibits CD8(+) T cell responses by targeting the aminopeptidase ERAP1. Nat Immunol 2011, 12:984-991.
34. Kochan G., Krojer T., Harvey D., Fischer R., Chen L., Vollmar M., et al. Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming. Proc Natl Acad Sci U S A 2011, 108:7745-7750.
35. Nguyen T.T., Chang S.C., Evnouchidou I., York I.A., Zikos C., Rock K.L., et al. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol 2011, 18:604-613.
36. Birtley J.R., Saridakis E., Stratikos E., Mavridis I.M. The crystal structure of human endoplasmic reticulum aminopeptidase 2 reveals the atomic basis for distinct roles in antigen processing. Biochemistry 2012, 51:286-295.
37. Li G.H., Cheung C.L., Xiao S.M., Lau K.S., Gao Y., Bow C.H., et al. Identification of QTL genes for BMD variation using both linkage and gene-based association approaches. Hum Genet 2011, 130:539-546.
38. Goto Y., Hattori A., Ishii Y., Tsujimoto M. Reduced activity of the hypertension-associated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-1. FEBS Lett 2006, 580:1833-1838.
39. Evnouchidou I., Kamal R.P., Seregin S.S., Goto Y., Tsujimoto M., Hattori A., et al. Cutting Edge: coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme. J Immunol 2011, 186:1909-1913.
40. Goto Y., Tanji H., Hattori A., Tsujimoto M. Glutamine-181 is crucial in the enzymatic activity and substrate specificity of human endoplasmic-reticulum aminopeptidase-1. Biochem J 2008, 416:109-116.
41. York I.A., Chang S.C., Saric T., Keys J.A., Favreau J.M., Goldberg A.L., et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol 2002, 3:1177-1184.
42. Hammer G.E., Gonzalez F., James E., Nolla H., Shastri N. In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Nat Immunol 2007, 8:101-108.
43. Hammer G.E., Gonzalez F., Champsaur M., Cado D., Shastri N. The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules. Nat Immunol 2006, 7:103-112.
44. Blanchard N., Kanaseki T., Escobar H., Delebecque F., Nagarajan N.A., Reyes-Vargas E., et al. Endoplasmic reticulum aminopeptidase associated with antigen processing defines the composition and structure of MHC class I peptide repertoire in normal and virus-infected cells. J Immunol 2010, 184:3033-3042.
45. Fruci D., Giacomini P., Nicotra M.R., Forloni M., Fraioli R., Saveanu L., et al. Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues. J Cell Physiol 2008, 216:742-749.
46. Fruci D., Ferracuti S., Limongi M.Z., Cunsolo V., Giorda E., Fraioli R., et al. Expression of endoplasmic reticulum aminopeptidases in EBV-B cell lines from healthy donors and in leukemia/lymphoma, carcinoma, and melanoma cell lines. J Immunol 2006, 176:4869-4879.
47. Cifaldi L., Lo Monaco E., Forloni M., Giorda E., Lorenzi S., Petrini S., et al. Natural killer cells efficiently reject lymphoma silenced for the endoplasmic reticulum aminopeptidase associated with antigen processing. Cancer Res 2011, 71:1597-1606.
48. Islam A., Adamik B., Hawari F.I., Ma G., Rouhani F.N., Zhang J., et al. Extracellular TNFR1 release requires the calcium-dependent formation of a nucleobindin 2-ARTS-1 complex. J Biol Chem 2006, 281:6860-6873.
49. Adamik B., Islam A., Rouhani F.N., Hawari F.I., Zhang J., Levine S.J. An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release. Biochem Biophys Res Commun 2008, 371:505-509.
50. Zikherman J., Weiss A. Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease. J Clin Invest 2011, 121:4618-4621.
51. Brewerton D.A., Caffrey M., Nicholls A., Walters D., James D.C. Acute anterior uveitis and HL-A 27. Lancet 1973, 302:994-996.
52. Pedersen O.B., Svendsen A.J., Ejstrup L., Skytthe A., Harris J.R., Junker P. Ankylosing spondylitis in Danish and Norwegian twins: occurrence and the relative importance of genetic vs. environmental effectors in disease causation. Scand J Rheumatol 2008, 37:120-126.
53. Burton P.R., Clayton D.G., Cardon L.R., Craddock N., Deloukas P., Duncanson A., et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 2007, 39:1329-1337.
54. Reveille J.D., Sims A.M., Danoy P., Evans D.M., Leo P., Pointon J.J., et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet 2010, 42:123-127.
55. Evans D.M., Spencer C.C., Pointon J.J., Su Z., Harvey D., Kochan G., et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 2011, 43:761-767.
56. Maksymowych W.P., Inman R.D., Gladman D.D., Reeve J.P., Pope A., Rahman P. Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in ankylosing spondylitis. Arthritis Rheum 2009, 60:1317-1323.
57. Harvey D., Pointon J.J., Evans D.M., Karaderi T., Farrar C., Appleton L.H., et al. Investigating the genetic association between ERAP1 and ankylosing spondylitis. Hum Mol Genet 2009, 18:4204-4212.
58. Pimentel-Santos F.M., Ligeiro D., Matos M., Mourao A.F., Sousa E., Pinto P., et al. Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population. Clin Exp Rheumatol 2009, 27:800-806.
59. Davidson S.I., Wu X., Liu Y., Wei M., Danoy P.A., Thomas G., et al. Association of ERAP1, but not IL23R, with ankylosing spondylitis in a Han Chinese population. Arthritis Rheum 2009, 60:3263-3268.
60. Pazar B., Safrany E., Gergely P., Szanto S., Szekanecz Z., Poor G. Association of ARTS1 gene polymorphisms with ankylosing spondylitis in the Hungarian population: the rs27044 variant is associated with HLA-B*2705 subtype in Hungarian patients with ankylosing spondylitis. J Rheumatol 2010, 37:379-384.
61. Choi C.B., Kim T.H., Jun J.B., Lee H.S., Shim S.C., Lee B., et al. ARTS1 polymorphisms are associated with ankylosing spondylitis in Koreans. Ann Rheum Dis 2010, 69:582-584.
62. Davidson S.I., Liu Y., Danoy P.A., Wu X., Thomas G.P., Jiang L., et al. Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese. Ann Rheum Dis 2011, 70:289-292.
63. Wu W., Ding Y., Chen Y., Hua Z., Liu H., Wang H., et al. Susceptibility to ankylosing spondylitis: evidence for the role of ERAP1, TGFb1 and TLR9 gene polymorphisms. Rheumatol Int 2011.
64. Szczypiorska M., Sanchez A., Bartolome N., Arteta D., Sanz J., Brito E., et al. ERAP1 polymorphisms and haplotypes are associated with ankylosing spondylitis susceptibility and functional severity in a Spanish population. Rheumatology (Oxford) 2011, 50:1969-1975.
65. Li C., Lin Z., Xie Y., Guo Z., Huang J., Wei Q., et al. ERAP1 is associated with ankylosing spondylitis in Han Chinese. J Rheumatol 2011, 38:317-321.
66. Tsui F.W., Haroon N., Reveille J.D., Rahman P., Chiu B., Tsui H.W., et al. Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis. Ann Rheum Dis 2010, 69:733-736.
67. Lee Y.H., Choi S.J., Ji J.D., Song G.G. Associations between ERAP1 polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis. Inflamm Res 2011, 60:999-1003.
68. Chen R., Yao L., Meng T., Xu W. The association between seven ERAP1 polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis involving 8,530 cases and 12,449 controls. Rheumatol Int 2012, 32:909-914.
69. Bluestone J.A., Herold K., Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010, 464:1293-1300.
70. Fung E.Y., Smyth D.J., Howson J.M., Cooper J.D., Walker N.M., Stevens H., et al. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes Immun 2009, 10:188-191.
71. Smyth D.J., Plagnol V., Walker N.M., Cooper J.D., Downes K., Yang J.H., et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008, 359:2767-2777.
72. Hafler D.A., Compston A., Sawcer S., Lander E.S., Daly M.J., De Jager P.L., et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007, 357:851-862.
73. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007, 447:661-678.
74. Robert C., Kupper T.S. Inflammatory skin diseases, T cells, and immune surveillance. N Engl J Med 1999, 341:1817-1828.
75. Lebwohl M. Psoriasis. Lancet 2003, 361:1197-1204.
76. Ayroldi E., Bastianelli A., Cannarile L., Petrillo M.G., Delfino D.V., Fierabracci A. A pathogenetic approach to autoimmune skin disease therapy: psoriasis and biological drugs, unresolved issues, and future directions. Curr Pharm Des 2011, 17:3176-3190.
77. Gudjonsson J.E., Johnston A., Sigmundsdottir H., Valdimarsson H. Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol 2004, 135:1-8.
78. Fitzgerald O., Winchester R. Psoriatic arthritis: from pathogenesis to therapy. Arthritis Res Ther 2009, 11:214.
79. Jabbari A., Johnson-Huang L.M., Krueger J.G. Role of the immune system and immunological circuits in psoriasis. G Ital Dermatol Venereol 2011, 146:17-30.
80. Hirota K., Duarte J.H., Veldhoen M., Hornsby E., Li Y., Cua D.J., et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 2011, 12:255-263.
81. Strange A., Capon F., Spencer C.C., Knight J., Weale M.E., Allen M.H., et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 2010, 42:985-990.
82. Sun L.D., Cheng H., Wang Z.X., Zhang A.P., Wang P.G., Xu J.H., et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 2010, 42:1005-1009.
83. Veal C.D., Capon F., Allen M.H., Heath E.K., Evans J.C., Jones A., et al. Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus. Am J Hum Genet 2002, 71:554-564.
84. Nair R.P., Stuart P.E., Nistor I., Hiremagalore R., Chia N.V., Jenisch S., et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006, 78:827-851.
85. Sanvito L., Constantinescu C.S., Gran B. Novel therapeutic approaches to autoimmune demyelinating disorders. Curr Pharm Des 2011, 17:3191-3201.
86. Guerini F.R., Cagliani R., Forni D., Agliardi C., Caputo D., Cassinotti A., et al. A functional variant in ERAP1 predisposes to multiple sclerosis. PLoS One 2012, 7:e29931.
87. Bianco A.M., Zanin V., Girardelli M., Magnolato A., Martellossi S., Tommasini A., et al. A common genetic background could explain early-onset Crohn's disease. Med Hypotheses 2012, 78:520-522.
88. Heyman M.B., Kirschner B.S., Gold B.D., Ferry G., Baldassano R., Cohen S.A., et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J Pediatr 2005, 146:35-40.
89. Barrett J.C., Hansoul S., Nicolae D.L., Cho J.H., Duerr R.H., Rioux J.D., et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008, 40:955-962.
90. Lacher M., Helmbrecht J., Schroepf S., Koletzko S., Ballauff A., Classen M., et al. NOD2 mutations predict the risk for surgery in pediatric-onset Crohn's disease. J Pediatr Surg 2010, 45:1591-1597.
91. Duerr R.H., Taylor K.D., Brant S.R., Rioux J.D., Silverberg M.S., Daly M.J., et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006, 314:1461-1463.
92. Franke A., McGovern D.P., Barrett J.C., Wang K., Radford-Smith G.L., Ahmad T., et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 2010, 42:1118-1125.