The link between HLA-B27 and SpA-new ideas on an old problem

Rheumatology (United Kingdom)

Volumn 51, Issue 9, 2012, Pages 1529-1539

  Mchugh, Kirsty ^a   Bowness, Paul ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Ankylosing spondylitis; Biologic therapies; Genetics; Genome wide association studies; HLA B27; Misfolding; Pathogenesis; Spondyloarthritis; Th17 cells

Indexed keywords

CELL SURFACE PROTEIN; HLA B27 ANTIGEN; HOMODIMER; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR;

ANKYLOSING SPONDYLITIS; ANTIGEN EXPRESSION; DISEASE ASSOCIATION; GENETIC ASSOCIATION; HUMAN; IMMUNOPATHOGENESIS; MOLECULAR RECOGNITION; PRIORITY JOURNAL; REVIEW; SPONDYLARTHRITIS; SPONDYLOARTHROPATHY; TH17 CELL;

BIOLOGICAL AGENTS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HLA-B27 ANTIGEN; HUMANS; SPONDYLITIS, ANKYLOSING; TH17 CELLS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84865338050     PISSN: 14620324     EISSN: 14620332     Source Type: Journal    
DOI: 10.1093/rheumatology/kes061     Document Type: Review

References (106)

1. Brewerton DA, Hart FD, Nicholls A et al. Ankylosing spondylitis and HL-A 27. Lancet 1973;1:904-7.
2. Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med 1973;288:704-6.
3. Brewerton DA, Caffrey M, Nicholls A, Walters D, James DC. HL-A 27 and arthropathies associated with ulcerative colitis and psoriasis. Lancet 1974;1:956-8.
4. Brewerton DA, Caffrey M, Nicholls A, Walters D, James DC. Letter: acute anterior uveitis and HL-A 27. Lancet 1974;1:464.
5. Kim TJ, Na KS, Lee HJ, Lee B, Kim TH. HLA-B27 homozygosity has no influence on clinical manifestations and functional disability in ankylosing spondylitis. Clin Exp Rheumatol 2009;27:574-9.
6. Jaakkola E, Herzberg I, Laiho K et al. Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis. Ann Rheum Dis 2006; 65:775-80.
7. Brown MA, Laval SH, Brophy S, Calin A. Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis. Ann Rheum Dis 2000;59:883-6.
8. Brown MA, Kennedy LG, MacGregor AJ et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum 1997; 40:1823-8.
9. Jarvinen P. Occurrence of ankylosing spondylitis in a nationwide series of twins. Arthritis Rheum 1995;38:381-3.
10. Pedersen OB, Svendsen AJ, Ejstrup L, Skytthe A, Junker P. On the heritability of psoriatic arthritis. Disease concordance among monozygotic and dizygotic twins. Ann Rheum Dis 2008;67:1417-21.
11. Burton PR, Clayton DG, Cardon LR et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 2007;39:1329-37.
12. Reveille JD, Sims AM, Danoy P et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet 2010;42:123-7.
13. Evans DM, Spencer CC, Pointon JJ 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;43:761-7.
14. Pointon JJ, Harvey D, Karaderi T et al. Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene. Genes Immun 2010;11:490-6.
15. Pointon JJ, Harvey D, Karaderi T et al. The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD). Ann Rheum Dis 2010;69:1243-6.
16. York IA, Chang SC, Saric T et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol 2002;3: 1177-84.
17. Saric T, Chang SC, Hattori A et al. An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Nat Immunol 2002;3: 1169-76.
18. Strange A, Capon F, Spencer CC et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 2010;42:985-90.
19. Harvey D, Pointon JJ, Evans DM et al. Investigating the genetic association between ERAP1 and ankylosing spondylitis. Hum Mol Genet 2009;18:4204-12.
20. Chang SC, Momburg F, Bhutani N, Goldberg AL. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a 'molecular ruler' mechanism. Proc Natl Acad Sci USA 2005;102:17107-12.
21. Nguyen TT, Chang SC, Evnouchidou I et al. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol 2011;18:604-13.
22. Kochan G, Krojer T, Harvey D et al. Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming. Proc Natl Acad Sci USA 2011;108:7745-50.
23. Rueda B, Orozco G, Raya E et al. The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis. Ann Rheum Dis 2008;67:1451-4.
24. Rahman P, Inman RD, Gladman DD et al. Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum 2008;58:1020-5.
25. Karaderi T, Harvey D, Farrar C et al. Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series. Rheumatology 2009; 48:386-9.
26. Layh-Schmitt G, Colbert RA. The interleukin-23/ interleukin-17 axis in spondyloarthritis. Curr Opin Rheumatol 2008;20:392-7.
27. Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine 2007;74:304-5.
28. Wang X, Lin Z, Wei Q, Jiang Y, Gu J. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatology Int 2009;29:1343-7.
29. Singh R, Aggarwal A, Misra R. Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy. J Rheumatol 2007;34:2285-90.
30. Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 2009; 60:1647-56.
31. Jandus C, Bioley G, Rivals JP et al. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 2008;58:2307-17.
32. Ciccia F, Bombardieri M, Principato A et al. Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis. Arthritis Rheum 2009;60:955-65.
33. Allen RL, O'Callaghan CA, McMichael AJ, Bowness P. Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure. J Immunol 1999;162:5045-8.
34. Antoniou AN, Ford S, Taurog JD, Butcher GW, Powis SJ. Formation of HLA-B27 homodimers and their relationship to assembly kinetics. J Biol Chem 2004;279:8895-902.
35. Dangoria NS, DeLay ML, Kingsbury DJ et al. HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum. J Biol Chem 2002;277:23459-68.
36. Santos SG, Lynch S, Campbell EC, Antoniou AN, Powis SJ. Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells. Arthritis Res Ther 2008;10:R100.
37. Bird LA, Peh CA, Kollnberger S et al. Lymphoblastoid cells express HLA-B27 homodimers both intracellularly and at the cell surface following endosomal recycling. Eur J Immunol 2003;33:748-59.
38. Kollnberger S, Bird L, Sun MY et al. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum 2002;46:2972-82.
39. Kollnberger S, Bird LA, Roddis M et al. HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired Ig-like receptors. J Immunol 2004;173:1699-710.
40. Madden DR, Gorga JC, Strominger JL, Wiley DC. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 1991;353: 321-5.
41. Merino E, Galocha B, Vazquez MN, Lopez de Castro JA. Disparate folding and stability of the ankylosing spondylitis-associated HLA-B*1403 and B*2705 proteins. Arthritis Rheum 2008;58:3693-704.
42. Urban RG, Chicz RM, Lane WS et al. A subset of HLA-B27 molecules contains peptides much longer than nonamers. Proc Natl Acad Sci USA 1994;91:1534-8.
43. Nixon DF, Townsend AR, Elvin JG et al. HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature 1988;336: 484-7.
44. Huet S, Nixon DF, Rothbard JB et al. Structural homologies between two HLA B27-restricted peptides suggest residues important for interaction with HLA B27. Int Immunol 1990;2:311-6.
45. Mear JP, Schreiber KL, Munz C et al. Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies. J Immunol 1999;163:6665-70.
46. Tran TM, Satumtira N, Dorris ML et al. HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP. J Immunol 2004;172:5110-9.
47. Peh CA, Burrows SR, Barnden M et al. HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading. Immunity 1998;8:531-42.
48. Benjamin RJ, Madrigal JA, Parham P. Peptide binding to empty HLA-B27 molecules of viable human cells. Nature 1991;351:74-7.
49. Ljunggren HG, Stam NJ, Ohlen C et al. Empty MHC class I molecules come out in the cold. Nature 1990;346:476-80.
50. Benjamin R, Parham P. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today 1990;11:137-42.
51. Oldstone MB. Molecular mimicry and autoimmune disease. Cell 1987;50:819-20.
52. Chen JH, Kono DH, Yong Z et al. A Yersinia pseudotuberculosis protein which cross-reacts with HLA-B27. J Immunol 1987;139:3003-11.
53. Hermann E, Yu DT, Meyer zum Buschenfelde KH, Fleischer B. HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis. Lancet 1993;342:646-50.
54. Appel H, Kuon W, Kuhne M et al. Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. Arthritis Res Ther 2004;6:R521-34.
55. Kuon W, Holzhutter HG, Appel H et al. Identification of HLA-B27-restricted peptides from the Chlamydia trachomatis proteome with possible relevance to HLA-B27-associated diseases. J Immunol 2001;167: 4738-46.
56. Ugrinovic S, Mertz A, Wu P, Braun J, Sieper J. A single nonamer from the Yersinia 60-kDa heat shock protein is the target of HLA-B27-restricted CTL response in Yersinia-induced reactive arthritis. J Immunol 1997;159: 5715-23.
57. May E, Dorris ML, Satumtira N et al. CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats. J Immunol 2003;170: 1099-105.
58. Boyle LH, Goodall JC, Opat SS, Gaston JS. The recognition of HLA-B27 by human CD4(+) T lymphocytes. J Immunol 2001;167:2619-24.
59. Khare SD, Hansen J, Luthra HS, David CS. HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m. J Clin Invest 1996;98:2746-55.
60. Khare SD, Luthra HS, David CS. Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies. J Exp Med 1995;182:1153-8.
61. Taurog JD. Arthritis in HLA-B27 transgenic animals. Am J Med Sci 1998;316:250-6.
62. Kingsbury DJ, Mear JP, Witte DP et al. Development of spontaneous arthritis in beta2-microglobulin-deficient mice without expression of HLA-B27: association with deficiency of endogenous major histocompatibility complex class I expression. Arthritis Rheum 2000;43: 2290-6.
63. Colbert RA. HLA-B27 misfolding: a solution to the spondyloarthropathy conundrum? Mol Med Today 2000;6: 224-30.
64. Pahl HL. Signal transduction from the endoplasmic reticulum to the cell nucleus. Physiol Rev 1999;79:683-701.
65. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2000;2: 326-32.
66. Todd DJ, Lee AH, Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008;8:663-74.
67. Pahl HL, Baeuerle PA. The ER-overload response: activation of NF-kappa B. Trends Biochem Sci 1997;22:63-7.
68. Kuang E, Wan Q, Li X et al. ER Ca2+ depletion triggers apoptotic signals for endoplasmic reticulum (ER) overload response induced by overexpressed reticulon 3 (RTN3/ HAP). J Cell Physiol 2005;204:549-59.
69. Turner MJ, Sowders DP, DeLay ML et al. HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J Immunol 2005;175: 2438-48.
70. Turner MJ, Delay ML, Bai S, Klenk E, Colbert RA. HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: implications for the pathogenesis of spondylarthritis-like disease. Arthritis Rheum 2007;56:215-23.
71. Gu J, Rihl M, Marker-Hermann E et al. Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles. J Rheumatol 2002;29:2159-64.
72. Tran TM, Dorris ML, Satumtira N et al. Additional human beta2-microglobulin curbs HLA-B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA-B27-transgenic rats. Arthritis Rheum 2006;54: 1317-27.
73. Taurog JD, Maika SD, Simmons WA, Breban M, Hammer RE. Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. J Immunol 1993;150: 4168-78.
74. Penttinen MA, Holmberg CI, Sistonen L, Granfors K. HLA-B27 modulates nuclear factor kappaB activation in human monocytic cells exposed to lipopolysaccharide. Arthritis Rheum 2002;46:2172-80.
75. Galocha B, de Castro JA. Folding of HLA-B27 subtypes is determined by the global effect of polymorphic residues and shows incomplete correspondence to ankylosing spondylitis. Arthritis Rheum 2008;58:401-12.
76. Galocha B, Lopez de Castro JA. Mutational analysis reveals a complex interplay of peptide binding and multiple biological features of HLA-B27. J Biol Chem 2010;285: 39180-90.
77. Lan CC, Tsai WC, Wu CS, Yu CL, Yu HS. Psoriatic patients with arthropathy show significant expression of free HLA class I heavy chains on circulating monocytes: a potential role in the pathogenesis of psoriatic arthropathy. Br J Dermatol 2004;151:24-31.
78. Raine T, Brown D, Bowness P et al. Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles. Rheumatology 2006;45:1338-44.
79. Tsai WC, Chen CJ, Yen JH et al. Free HLA class I heavy chain-carrying monocytes-a potential role in the pathogenesis of spondyloarthropathies. J Rheumatol 2002;29: 966-72.
80. Colonna M, Nakajima H, Navarro F, Lopez-Botet M. A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells. J Leukoc Biol 1999;66:375-81.
81. Lanier LL. Follow the leader: NK cell receptors for classical and nonclassical MHC class I. Cell 1998;92: 705-7.
82. Brown D, Trowsdale J, Allen R. The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens 2004;64:215-25.
83. Colonna M, Navarro F, Bellon T et al. A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med 1997;186:1809-18.
84. Perez-Villar JJ, Melero I, Navarro F et al. The CD94/ NKG2-A inhibitory receptor complex is involved in natural killer cell-mediated recognition of cells expressing HLA-G1. J Immunol 1997;158:5736-43.
85. Ugolini S, Arpin C, Anfossi N et al. Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T cells. Nat Immunol 2001;2: 430-5.
86. Ristich V, Liang S, Zhang W, Wu J, Horuzsko A. Tolerization of dendritic cells by HLA-G. Eur J Immunol 2005;35:1133-42.
87. Chang CC, Ciubotariu R, Manavalan JS et al. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 2002;3:237-43.
88. Colonna M, Samaridis J, Cella M et al. Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J Immunol 1998;160:3096-100.
89. Chan AT, Kollnberger SD, Wedderburn LR, Bowness P. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum 2005;52: 3586-95.
90. Bowness P, Ridley A, Shaw J et al. Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J Immunol 2011; 186:2672-80.
91. Hacquard-Bouder C, Chimenti MS, Giquel B et al. Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T cells: selective impairment of costimulatory molecule engagement by mature HLA-B27. Arthritis Rheum 2007;56:1478-89.
92. Hacquard-Bouder C, Falgarone G, Bosquet A et al. Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy. Arthritis Rheum 2004;50: 1624-35.
93. Stagg AJ, Breban M, Hammer RE, Knight SC, Taurog JD. Defective dendritic cell (DC) function in a HLA-B27 transgenic rat model of spondyloarthropathy (SpA). Adv Exp Med Biol 1995;378:557-9.
94. Schett G. Review: immune cells and mediators of inflammatory arthritis. Autoimmunity 2008;41:224-9.
95. Wong PK, Quinn JM, Sims NA et al. Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum 2006;54:158-68.
96. Song IH, Heldmann F, Rudwaleit M et al. Different response to rituximab in tumor necrosis factor blocker-naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: a twenty-four-week clinical trial. Arthritis Rheum 2010;62:1290-7.
97. Baeten D, Sieper J, Emery P et al. The anti-IL17A monoclonal antibody secukinumab (AIN457) showed good safety and efficacy in the treatment of active ankylosing spondylitis. Arthritis Rheum 2010;62(Suppl): S3840-1.
98. Gottlieb A, Menter A, Mendelsohn A et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet 2009;373: 633-40.
99. Armaka M, Apostolaki M, Jacques P et al. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med 2008;205:331-7.
100. Cargill M, Schrodi SJ, Chang M et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007;80:273-90.
101. Duerr RH, Taylor KD, Brant SR et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006;314:1461-3.
102. Zhang XJ, Huang W, Yang S et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009;41:205-10.
103. Cortes A, Brown MA. Promise and pitfalls of the Immunochip. Arthritis Res Ther 2010;13:101.
104. Danoy P, Pryce K, Hadler J et al. Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease. PLoS Genet 2010; 6:e1001195.
105. Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 2008;8: 458-66.
106. Libioulle C, Louis E, Hansoul S et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet 2007;3:e58.