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Budowa i funkcja ludzkich antygenów zgodności tkankowej. Część 3. Rola antygenów MHC w chorobach reumatycznych

Krzysztof Wiktorowicz, Krzysztof Kaszkowiak, Włodzimierz Samborski
DOI: 10.5603/FR.2019.0005
·
Forum Reumatologiczne 2019;5(1):33-42.

open access

Vol 5, No 1 (2019)
Prace poglądowe
Published online: 2019-04-04

Abstract

Ekspresja określonych alleli zgodności tkankowej stanowi czynnik ryzyka chorób reumatycznych. W reumatoidalnym zapaleniu stawów jest to obecność antygenów HLA-DRB1, z charakterystyczną sekwencją pięciu aminokwasów (glutamina, lizyna, arginina, alanina) w pozycjach od 70 do 74 łańcucha, nazywanych najczęściej wspólnym epitopem. Charakterystyczna dla zesztywniającego zapalenie stawów kręgosłupa jest ekspresja antygenu zgodności tkankowej HLA-B27, który może prezentować nieprawidłowo przetworzone peptydy antygenowe. Wydaje się, że cząsteczki HLA-B27 mogą z większą wydajnością prezentować autoreaktywnym limfocytom T patogenne peptydy bakteryjne albo endogenne peptydy artrytogenne. W biologii chorób reumatycznych ważną rolę mogą odgrywać także polimorfizmy pojedynczego nukleotydu (SNP, single nucleotide polymorphism) czy mechanizmy epigenetyczne, wpływające na ekspresję genów.

Forum Reumatol. 2019, tom 5, nr 1: 33–42

Abstract

Ekspresja określonych alleli zgodności tkankowej stanowi czynnik ryzyka chorób reumatycznych. W reumatoidalnym zapaleniu stawów jest to obecność antygenów HLA-DRB1, z charakterystyczną sekwencją pięciu aminokwasów (glutamina, lizyna, arginina, alanina) w pozycjach od 70 do 74 łańcucha, nazywanych najczęściej wspólnym epitopem. Charakterystyczna dla zesztywniającego zapalenie stawów kręgosłupa jest ekspresja antygenu zgodności tkankowej HLA-B27, który może prezentować nieprawidłowo przetworzone peptydy antygenowe. Wydaje się, że cząsteczki HLA-B27 mogą z większą wydajnością prezentować autoreaktywnym limfocytom T patogenne peptydy bakteryjne albo endogenne peptydy artrytogenne. W biologii chorób reumatycznych ważną rolę mogą odgrywać także polimorfizmy pojedynczego nukleotydu (SNP, single nucleotide polymorphism) czy mechanizmy epigenetyczne, wpływające na ekspresję genów.

Forum Reumatol. 2019, tom 5, nr 1: 33–42

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Keywords

HLA-DRB1; wspólny epitop; HLA-B27; prezentacja antygenu

About this article
Title

Budowa i funkcja ludzkich antygenów zgodności tkankowej. Część 3. Rola antygenów MHC w chorobach reumatycznych

Journal

Forum Reumatologiczne

Issue

Vol 5, No 1 (2019)

Pages

33-42

Published online

2019-04-04

DOI

10.5603/FR.2019.0005

Bibliographic record

Forum Reumatologiczne 2019;5(1):33-42.

Keywords

HLA-DRB1
wspólny epitop
HLA-B27
prezentacja antygenu

Authors

Krzysztof Wiktorowicz
Krzysztof Kaszkowiak
Włodzimierz Samborski

References (85)
  1. MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000; 43(1): 30–37.
  2. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016; 388(10055): 2023–2038.
  3. Knevel R, Huizinga TWJ, Kurreeman F. Genomic Influences on Susceptibility and Severity of Rheumatoid Arthritis. Rheum Dis Clin North Am. 2017; 43(3): 347–361.
  4. Terao C, Raychaudhuri S, Gregersen PK. Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis. Annu Rev Genomics Hum Genet. 2016; 17: 273–301.
  5. Yarwood A, Huizinga TWJ, Worthington J. The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA. Rheumatology (Oxford). 2016; 55(2): 199–209.
  6. ROSE HM, RAGAN C. Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis. Proc Soc Exp Biol Med. 1948; 68(1): 1–6.
  7. Viatte S, Barton A. Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. Semin Immunopathol. 2017; 39(4): 395–408.
  8. van Drongelen V, Holoshitz J. Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis. Rheum Dis Clin North Am. 2017; 43(3): 363–376.
  9. Kampstra ASB, Toes REM. HLA class II and rheumatoid arthritis: the bumpy road of revelation. Immunogenetics. 2017; 69(8-9): 597–603.
  10. Michou L, Croiseau P, Petit-Teixeira E, et al. European Consortium on Rheumatoid Arthritis Families. Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis. Arthritis Res Ther. 2006; 8(3): R79.
  11. de Almeida DE, Ling S, Holoshitz J. New insights into the functional role of the rheumatoid arthritis shared epitope. FEBS Lett. 2011; 585(23): 3619–3626.
  12. Derksen VF, Huizinga TWJ, van der Woude D. The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin Immunopathol. 2017; 39(4): 437–446.
  13. van der Woude D, Toes REM. The contribution of autoantibodies to post-translationally modified proteins to inflammatory arthritis. Curr Opin Rheumatol. 2017; 29(2): 195–200.
  14. Scally SW, Petersen J, Law SC, et al. A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med. 2013; 210(12): 2569–2582.
  15. Sidney J, Becart S, Zhou M, et al. Citrullination only infrequently impacts peptide binding to HLA class II MHC. PLoS One. 2017; 12(5): e0177140.
  16. Kampstra ASB, van Heemst J, Moustakas AK, et al. The increased ability to present citrullinated peptides is not unique to HLA-SE molecules: arginine-to-citrulline conversion also enhances peptide affinity for HLA-DQ molecules. Arthritis Res Ther. 2016; 18(1): 254.
  17. Reed E, Jiang X, Kharlamova N, et al. Antibodies to carbamylated α-enolase epitopes in rheumatoid arthritis also bind citrullinated epitopes and are largely indistinct from anti-citrullinated protein antibodies. Arthritis Res Ther. 2016; 18(1): 96.
  18. Raychaudhuri S, Sandor C, Stahl EA, et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet. 2012; 44(3): 291–296.
  19. Viatte S, Plant D, Han B, et al. Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response. JAMA. 2015; 313(16): 1645–1656.
  20. Han B, Diogo D, Eyre S, et al. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. Am J Hum Genet. 2014; 94(4): 522–532.
  21. Okada Y, Suzuki A, Ikari K, et al. Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis. Am J Hum Genet. 2016; 99(2): 366–374.
  22. Zanelli E, Breedveld FC, de Vries RR. HLA association with autoimmune disease: a failure to protect? Rheumatology (Oxford). 2000; 39(10): 1060–1066.
  23. Singal DP, Li J, Zhu Y. HLA class III region and susceptibility to rheumatoid arthritis. Clin Exp Rheumatol. 2000; 18(4): 485–491.
  24. Yau ACY, Tuncel J, Haag S, et al. Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis. Proc Natl Acad Sci U S A. 2016; 113(26): E3716–E3724.
  25. van Heemst J, Jansen DT, Polydorides S, et al. Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis. Nat Commun. 2015; 6: 6681.
  26. Lee YH, Bae SC, Kim JH, et al. Meta-analysis of the association between functional MICA-TM polymorphisms and systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis. Z Rheumatol. 2015; 74(2): 146–152.
  27. Martinez A, Fernandez-Arquero M, Balsa A, et al. Primary association of a MICA allele with protection against rheumatoid arthritis. Arthritis Rheum. 2001; 44(6): 1261–1265.
  28. Kirsten H, Petit-Teixeira E, Scholz M, et al. Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study. Arthritis Res Ther. 2009; 11(3): R60.
  29. López-Arbesu R, Ballina-García FJ, Alperi-López M, et al. MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility. Rheumatology (Oxford). 2007; 46(3): 426–430.
  30. Iwaszko M, Świerkot J, Kolossa K, et al. Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy. Clin Exp Immunol. 2015; 182(3): 270–277.
  31. Rizzo R, Farina I, Bortolotti D, et al. HLA-G may predict the disease course in patients with early rheumatoid arthritis. Hum Immunol. 2013; 74(4): 425–432.
  32. Lemire M. On the association between rheumatoid arthritis and classical HLA class I and class II alleles predicted from single-nucleotide polymorphism data. BMC Proc. 2009; 3 Suppl 7: S33.
  33. Vignal C, Bansal AT, Balding DJ, et al. Genetic association of the major histocompatibility complex with rheumatoid arthritis implicates two non-DRB1 loci. Arthritis Rheum. 2009; 60(1): 53–62.
  34. Toussirot E, Sauvageot C, Chabod J, et al. The association of HLA-DM genes with rheumatoid arthritis in Eastern France. Hum Immunol. 2000; 61(3): 303–308.
  35. Moxley G, Han J. HLA DMA and DMB show no association with rheumatoid arthritis in US Caucasians. Eur J Immunogenet. 2001; 28(5): 539–543.
  36. Eike MC, Skinningsrud B, Ronninger M, et al. CIITA gene variants are associated with rheumatoid arthritis in Scandinavian populations. Genes Immun. 2012; 13(5): 431–436.
  37. Bowness P. HLA-B27. Annu Rev Immunol. 2015; 33: 29–48.
  38. Vitulano C, Tedeschi V, Paladini F, et al. The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis. Clin Exp Immunol. 2017; 190(3): 281–290.
  39. Urban RG, Chicz RM, Lane WS, et al. A subset of HLA-B27 molecules contains peptides much longer than nonamers. Proc Natl Acad Sci U S A. 1994; 91(4): 1534–1538.
  40. Uchanska-Ziegler B, Ziegler A, Schmieder P. Structural and dynamic features of HLA-B27 subtypes. Curr Opin Rheumatol. 2013; 25(4): 411–8.
  41. Abualrous ET, Fritzsche S, Hein Z, et al. F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins. Eur J Immunol. 2015; 45(4): 1248–1257.
  42. Cortes A, Hadler J, Pointon JP, et al. International Genetics of Ankylosing Spondylitis Consortium (IGAS), Australo-Anglo-American Spondyloarthritis Consortium (TASC), Groupe Française d'Etude Génétique des Spondylarthrites (GFEGS), Nord-Trøndelag Health Study (HUNT), Spondyloarthritis Research Consortium of Canada (SPARCC), Wellcome Trust Case Control Consortium 2 (WTCCC2). Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet. 2013; 45(7): 730–738.
  43. Reeves E, Colebatch-Bourn A, Elliott T, et al. Functionally distinctERAP1allotype combinations distinguish individuals with Ankylosing Spondylitis. Proceedings of the National Academy of Sciences. 2014; 111(49): 17594–17599.
  44. Sanz-Bravo A, Alvarez-Navarro C, Martín-Esteban A, et al. Ranking the Contribution of Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphisms to Shaping the HLA-B*27 Peptidome. Mol Cell Proteomics. 2018; 17(7): 1308–1323.
  45. Evans DM, Spencer CCA, Pointon JJ, et al. Spondyloarthritis Research Consortium of Canada (SPARCC), Australo-Anglo-American Spondyloarthritis Consortium (TASC), Wellcome Trust Case Control Consortium 2 (WTCCC2). 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(8): 761–767.
  46. Cortes A, Pulit SL, Leo PJ, et al. Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nat Commun. 2015; 6: 7146.
  47. Vargas-Alarcón G, Gamboa R, Zuñiga J, et al. Association study of LMP gene polymorphisms in Mexican patients with spondyloarthritis. Hum Immunol. 2004; 65(12): 1437–1442.
  48. Haroon N, Maksymowych W, Rahman P, et al. Radiographic severity in ankylos-ing spondylitis is associated with polymorphism in large multifunctionalpeptidase 2 (LMP2) in the SPARCC cohort. Arthritis Rheum. 2011; 64: 1119–26.
  49. Qian Y, Wang G, Xue F, et al. Genetic association between TAP1 and TAP2 polymorphisms and ankylosing spondylitis: a systematic review and meta-analysis. Inflamm Res. 2017; 66(8): 653–661.
  50. Illing PT, Vivian JP, Dudek NL, et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. 2012; 486(7404): 554–558.
  51. Colbert RA, Tran TM, Layh-Schmitt G. HLA-B27 misfolding and ankylosing spondylitis. Mol Immunol. 2014; 57(1): 44–51.
  52. Antoniou AN, Guiliano DB, Lenart I, et al. The oxidative folding and misfolding of human leukocyte antigen-b27. Antioxid Redox Signal. 2011; 15(3): 669–684.
  53. McHugh K, Bowness P. The link between HLA-B27 and SpA--new ideas on an old problem. Rheumatology (Oxford). 2012; 51(9): 1529–1539.
  54. Wong-Baeza I, Ridley A, Shaw J, et al. KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis. J Immunol. 2013; 190(7): 3216–3224.
  55. Robinson PC, Brown MA. Genetics of ankylosing spondylitis. Mol Immunol. 2014; 57(1): 2–11.
  56. Díaz-Peña R, López-Vázquez A, López-Larrea C. Old and new HLA associations with ankylosing spondylitis. Tissue Antigens. 2012; 80(3): 205–213.
  57. Wei JCC, Tsai WC, Lin HS, et al. HLA-B60 and B61 are strongly associated with ankylosing spondylitis in HLA-B27-negative Taiwan Chinese patients. Rheumatology (Oxford). 2004; 43(7): 839–842.
  58. Yamaguchi A, Tsuchiya N, Mitsui H, et al. Association of HLA-B39 with HLA-B27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients. Evidence for a role of the peptide-anchoring B pocket. Arthritis Rheum. 1995; 38(11): 1672–1677.
  59. Bown MA, Jin R, Wordsworth BP, et al. et al.. HLA Class I and II associations of anky-losing spondylitis. Arthritis Rheum. 2009; 60(Suppl 10): 11716–11721.
  60. Breban M, Costantino F, André C, et al. Revisiting MHC genes in spondyloarthritis. Curr Rheumatol Rep. 2015; 17(6): 516.
  61. Paladini F, Belfiore F, Cocco E, et al. HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia. Arthritis Res Ther. 2009; 11(6): R171.
  62. Santos MR, Couto AR, Foroni I, et al. Non-classical human leucocyte antigens in ankylosing spondylitis: possible association with HLA-E and HLA-F. RMD Open. 2018; 4(1): e000677.
  63. Zhou X, Wang J, Zou H, et al. MICA, a gene contributing strong susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2014; 73(8): 1552–1557.
  64. Lenz TL, Deutsch AJ, Han B, et al. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases. Nat Genet. 2015; 47(9): 1085–1090.
  65. Wei WH, Loh CY, Worthington J, et al. Immunochip Analyses of Epistasis in Rheumatoid Arthritis Confirm Multiple Interactions within MHC and Suggest Novel Non-MHC Epistatic Signals. J Rheumatol. 2016; 43(5): 839–845.
  66. Wei WH, Bowes J, Plant D, et al. Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis. Sci Rep. 2016; 6: 25014.
  67. Spurlock CF, Tossberg JT, Olsen NJ, et al. Cutting Edge: Chronic NF-κB Activation in CD4+ T Cells in Rheumatoid Arthritis Is Genetically Determined by HLA Risk Alleles. J Immunol. 2015; 195(3): 791–795.
  68. Khan MA. An Update on the Genetic Polymorphism of HLA-B*27 With 213 Alleles Encompassing 160 Subtypes (and Still Counting). Curr Rheumatol Rep. 2017; 19(2): 9.
  69. Saad MN, Mabrouk MS, Eldeib AM, et al. Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis. J Adv Res. 2016; 7(1): 1–16.
  70. Kim K, Bang SY, Lee HS, et al. Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, Wellcome Trust Case Control Consortium. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012; 44(12): 1336–1340.
  71. Reveille JD, Sims AM, Danoy P, et al. Australo-Anglo-American Spondyloarthritis Consortium (TASC). Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010; 42(2): 123–127.
  72. Khan MA. Polymorphism of HLA-B27: 105 subtypes currently known. Curr Rheumatol Rep. 2013; 15(10): 362.
  73. Blanco-Gelaz MA, Suárez-Alvarez B, González S, et al. The amino acid at position 97 is involved in folding and surface expression of HLA-B27. Int Immunol. 2006; 18(1): 211–220.
  74. Isernhagen A, Malzahn D, Bickeböller H, et al. Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks. Front Immunol. 2016; 7: 588.
  75. Achour Y, Ben Hamad M, Chaabane S, et al. Analysis of two susceptibility SNPs in HLA region and evidence of interaction between rs6457617 in HLA-DQB1 and HLA-DRB1*04 locus on Tunisian rheumatoid arthritis. J Genet. 2017; 96(6): 911–918.
  76. Li Z, Brown MA. Progress of genome-wide association studies of ankylosing spondylitis. Clin Transl Immunology. 2017; 6(12): e163.
  77. Ramsuran V, Kulkarni S, O'huigin C, et al. Epigenetic regulation of differential HLA-A allelic expression levels. Hum Mol Genet. 2015; 24(15): 4268–4275.
  78. Moreau P, Flajollet S, Carosella ED. Non-classical transcriptional regulation of HLA-G: an update. J Cell Mol Med. 2009; 13(9B): 2973–2989.
  79. Wright KL, Ting JPY. Epigenetic regulation of MHC-II and CIITA genes. Trends Immunol. 2006; 27(9): 405–412.
  80. Kato M, Yasuda S, Atsumi T. The role of genetics and epigenetics in rheumatic diseases: are they really a target to be aimed at? Rheumatol Int. 2018; 38(8): 1333–1338.
  81. Kolarz B, Majdan M. Epigenetyczne uwarunkowania reumatoidalnego zapalenia stawów: wpływ metylacji DNA i modyfikacji białek histonowych. Postępy Hig Med Dosw (online. 2017; 71: 1070–1079.
  82. Ballestar E, Li T. New insights into the epigenetics of inflammatory rheumatic diseases. Nat Rev Rheumatol. 2017; 13(10): 593–605.
  83. Liu Y, Aryee MJ, Padyukov L, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol. 2013; 31(2): 142–147.
  84. van Steenbergen HW, Luijk R, Shoemaker R, et al. Differential methylation within the major histocompatibility complex region in rheumatoid arthritis: a replication study. Rheumatology (Oxford). 2014; 53(12): 2317–2318.
  85. Guo S, Zhu Qi, Jiang T, et al. Genome-wide DNA methylation patterns in CD4+ T cells from Chinese Han patients with rheumatoid arthritis. Mod Rheumatol. 2017; 27(3): 441–447.

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