nach oben

Current Rheumatology Reports

Erschienen in:

11.11.2023

HLA-B*27 and Ankylosing Spondylitis: 50 Years of Insights and Discoveries

verfasst von: Muhammad A. Khan

Erschienen in: Current Rheumatology Reports | Ausgabe 12/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

To commemorate the 50th anniversary of the groundbreaking discovery of a remarkably strong association between HLA-B*27 and ankylosing spondylitis (AS).

Recent Findings

In addition to HLA-B*27, more than 116 other recognized genetic risk variants have been identified, while epigenetic factors largely remain unexplored in this context. Among patients with AS who carry the HLA-B*27 gene, clonally expanded CD8 + T cells can be found in their bloodstream and within inflamed tissues. Moreover, the α and β chain motifs of these T-cell receptors demonstrate a distinct affinity for certain self- and microbial-derived peptides, leading to an autoimmune response that ultimately results in the onset of the disease. These distinctive peptide-binding and presentation characteristics are a hallmark of the disease-associated HLA-B*27:05 subtype but are absent in HLA-B*27:09, a subtype not associated with the disease, differing by only a single amino acid. This discovery represents a significant advancement in unraveling the 50-year-old puzzle of how HLA-B*27 contributes to the development of AS.

Summary

These findings will significantly accelerate the process of identifying peptides, both self- and microbial-derived, that instigate autoimmunity. This, in return, will pave the way for the development of more accurate and effective targeted treatments. Moreover, the discovery of improved biomarkers, in conjunction with the emerging technology of electric field molecular fingerprinting, has the potential to greatly bolster early diagnosis capabilities. A very recently published groundbreak paper underscores the remarkable effectiveness of targeting and eliminating disease-causing T cells in a HLA-B*27 patients with AS. This pivotal advancement not only signifies a paradigm shift but also bolsters the potential for preventing the disease in individuals carrying high-risk genetic variants.

Caffrey MF, James DC. Human lymphocyte antigen association in ankylosing spondylitis. Nature. 1973;242(5393):121. https://doi.org/10.1038/242121a0.CrossRefPubMed

Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973;1(7809):904–7. https://doi.org/10.1016/s0140-6736(73)91360-3.CrossRefPubMed

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(14):704–6. https://doi.org/10.1056/NEJM197304052881403.CrossRefPubMed

Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum. 2005;52(4):1000–8. https://doi.org/10.1002/art.20990.CrossRefPubMed

Akkoc N, Khan MA. Radiographic axial spondyloarthritis versus ankylosing spondylitis. Clin Exp Rheumatol. 2016;34(1 Suppl 95):S7.PubMed

Khan MA, van der Linden S. Axial spondyloarthritis: a better name for an old disease: a step toward uniform reporting. ACR Open Rheumatol. 2019;1(5):336–9. https://doi.org/10.1002/acr2.11044.CrossRefPubMedPubMedCentral

Robinson PC, van der Linden S, Khan MA, et al. Axial spondyloarthritis: concept, construct, classification, and implications for therapy. Nat Rev Rheumatol. 2021;17:109–18. https://doi.org/10.1038/s41584-020-00552-4.CrossRefPubMed

Thorsby E. HL-A antigens and genes. I. A study of unrelated Norwegians. Vox Sang. 1969;17(2):81–92. https://doi.org/10.1111/j.1423-0410.1969.tb00377.x.CrossRefPubMed

Allen E, Amos DB, Batchelor R. Joint report of 4th International Histocompatibility Workshop. In: Terasaki PI, editor. Histocompatibility Testing Copenhagen 1970;17–47.: Munksgaard; 1970.

10.

Robinson J, Barker DJ, Georgiou X, Cooper MA, Flicek P, Marsh SGE. IPD-IMGT/HLA database. Nucleic Acids Res. 2020;48(D1):D948–55. https://doi.org/10.1093/nar/gkz950.CrossRefPubMed

11.

Brewerton DA. Discovery: HLA and disease. Curr Opin Rheumatol. 2003;15(4):369–73. https://doi.org/10.1097/00002281-200307000-00001.CrossRefPubMed

12.

James DC. HLA-B27 in clinical medicine–historical reflections on the discovery of the disease association. Br J Rheumatol. 1983;22(4 Suppl 2):20–4. https://doi.org/10.1093/rheumatology/xxii.suppl_2.20.CrossRefPubMed

13.

Sturrock RD. Human leukocyte antigen B27. Clin Med (Lond). 2010;10(2):162–3. https://doi.org/10.7861/clinmedicine.10-2-162.CrossRefPubMed

14.

Spencer DG, Sturrock RD, Buchanan WW. Ankylosing spondylitis: yesterday and today. Med Hist. 1980;24(1):60–9. https://doi.org/10.1017/s0025727300039788.CrossRefPubMedPubMedCentral

15.

Stecher RM, Hauser H. Ankylosing spondylitis; report of occurrence in 2 brothers. Am J Roentgenol Radium Ther. 1946;56(5):601–6.PubMed

16.

Stecher RM, Hersh AH. Familial occurrence of ankylosing spondylitis. Br J Phys Med. 1955;18(8):176–83.PubMed

17.

Brewerton DA, Caffrey M, Nicholls A, Walters D, James DC. Acute anterior uveitis and HL-A 27. Lancet. 1973;302(7836):994–6. https://doi.org/10.1016/s0140-6736(73)91090-8.CrossRefPubMed

18.

Brewerton DA, Caffrey M, Nicholls A, Walters D, Oates JK, James DC. Reiter’s disease and HL-A 27. Lancet. 1973;302(7836):996–8. https://doi.org/10.1016/s0140-6736(73)91091-x.CrossRefPubMed

19.

Khan MA. HLA-B27 and its pathogenic role. J Clin Rheumatol. 2008;14(1):50–2. https://doi.org/10.1097/RHU.0b013e3181637a38.CrossRefPubMed

20.

Khan MA, Kushner I, Braun WE. Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum. 1977;20(4):909–12. https://doi.org/10.1002/art.1780200401.CrossRefPubMed

21.

Khan MA, Braun WE, Kushner I, Grecek DE, Muir WA, Steinberg AG. HLA B27 in ankylosing spondylitis: differences in frequency and relative risk in American Blacks and Caucasians. J Rheumatol Suppl. 1977;3:39–43.PubMed

22.

Khan MA, Kushner I, Braun WE. Genetic heterogeneity in primary ankylosing spondylitis. J Rheumatol. 1980;7(3):383–6.PubMed

23.

Feldtkeller E, Khan A, van der Heijde D, van der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int. 2003;23(2):61–6. https://doi.org/10.1007/s00296-002-0237-4.CrossRefPubMed

24.

Akkoc N, Yarkan H, Kenar G, Khan MA. Ankylosing spondylitis: HLA-B*27-positive versus HLA-B*27-negative disease. Curr Rheumatol Rep. 2017;19(5):26. https://doi.org/10.1007/s11926-017-0654-8.CrossRefPubMed

25.

Cui Z, Hou G, Meng X, Feng H, He B, Tian Y. Bidirectional causal associations between inflammatory bowel disease and ankylosing spondylitis: a two-sample Mendelian randomization analysis. Front Genet. 2020;19(11):587876. https://doi.org/10.3389/fgene.2020.587876.CrossRef

26.

Arévalo M, Gratacós Masmitjà J, Moreno M, Calvet J, Orellana C, Ruiz D, et al; REGISPONSER group. Influence of HLA-B27 on the ankylosing spondylitis phenotype: results from the REGISPONSER database. Arthritis Res Ther. 2018;20(1):221. https://doi.org/10.1186/s13075-018-1724-7. Erratum in: Arthritis Res Ther. 2020 Jun 11;22(1):140.

27.

• Li Z, van der Linden SM, Khan MA, Baumberger H, Zandwijk HV, Khan MK, Villiger PM, Brown MA. Heterogeneity of axial spondyloarthritis: genetics, sex, and structural damage matter. RMD Open. 2022;8(1):e002302. https://doi.org/10.1136/rmdopen-2022-002302. (This study provides evidence for a high degree of heterogeneity of primary AS and recommends that stratified or adjusted analysis of effectiveness studies be performed, taking genetics, sex, and radiographic damage (sacroiliitis) into account.)CrossRefPubMedPubMedCentral

28.

Brown MA, Xu H, Li Z. Genetics and the axial spondyloarthritis spectrum. Rheumatology (Oxford). 2020;59(Suppl4):iv58–66. https://doi.org/10.1093/rheumatology/keaa464.CrossRefPubMed

29.

Zhang S, Peng L, Li Q, Zhao J, Xu D, Zhao J, et al. Spectrum of spondyloarthritis among Chinese populations. Curr Rheumatol Rep. 2022;24(8):247–58. https://doi.org/10.1007/s11926-022-01079-1.CrossRefPubMedPubMedCentral

30.

Fröhlich F, Micheroli R, Hebeisen M, Kissling S, Bürki K, Exer P, et al. HLA-B27 as a predictor of effectiveness of treatment with TNF inhibitors in axial spondyloarthritis: data from the Swiss Clinical Quality Management Registry. Clin Rheumatol. 2023;42(5):1267–74. https://doi.org/10.1007/s10067-022-06490-8.CrossRefPubMed

31.

Stovall R, van der Horst-Bruinsma IE, Liu SH, Rusman T, Gensler LS. Sexual dimorphism in the prevalence, manifestation and outcomes of axial spondyloarthritis. Nat Rev Rheumatol. 2022;18(11):657–69. https://doi.org/10.1038/s41584-022-00833-0.CrossRefPubMed

32.

Khan MA, van der Linden SM, Kushner I, Valkenburg HA, Cats A. Spondylitic disease without radiologic evidence of sacroiliitis in relatives of HLA-B27 positive ankylosing spondylitis patients. Arthritis Rheum. 1985;28(1):40–3. https://doi.org/10.1002/art.1780280107.CrossRefPubMed

33.

Khan MA, van der Linden SM. A wider spectrum of spondyloarthropathies. Semin Arthritis Rheum. 1990;20(2):107–13. https://doi.org/10.1016/0049-0172(90)90023-9.CrossRefPubMed

34.

Malaviya AN, Kalyani A, Rawat R, Gogia SB. Comparison of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) from a single rheumatology clinic in New Delhi. Int J Rheum Dis. 2015;18(7):736–41. https://doi.org/10.1111/1756-185X.12579.CrossRefPubMed

35.

Bittar M, Yong WC, Magrey M, Khan MA. Worldwide differences in clinical phenotype of axial spondyloarthritis. Curr Rheumatol Rep. 2021;23(10):76. https://doi.org/10.1007/s11926-021-01043-5.CrossRefPubMed

36.

Burgos-Varga R, Wei JC, Rahman MU, Akkoc N, Haq SA, Hammoudeh M, et al. The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study. Arthritis Res Ther. 2016;18(1):132. https://doi.org/10.1186/s13075-016-1027-9.CrossRefPubMedPubMedCentral

37.

Haroon NN, Paterson JM, Li P, Haroon N. Increasing proportion of female patients with ankylosing spondylitis: a population-based study of trends in the incidence and prevalence of AS. BMJ Open. 2014;4(12):e006634. https://doi.org/10.1136/bmjopen-2014-006634.CrossRefPubMedPubMedCentral

38.

Tournadre A, Pereira B, Lhoste A, Dubost JJ, Ristori JM, Claudepierre P, et al. Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort. Arthritis Care Res (Hoboken). 2013;65(9):1482–9. https://doi.org/10.1002/acr.22001.CrossRefPubMed

39.

Rusman T, van Vollenhoven RF, van der Horst-Bruinsma IE. Gender differences in axial spondyloarthritis: women are not so lucky. Curr Rheumatol Rep. 2018;20(6):35. https://doi.org/10.1007/s11926-018-0744-2.CrossRefPubMedPubMedCentral

40.

Baumberger H, Khan M. SAT0417|Gradual progressive change to equal prevalence of ankylosing spondylitis among males and females in Switzerland: data from the Swiss ankylosing spondylitis society (SVMB). Ann Rheumatic Dis. 2017;76(Suppl 2):929-. https://doi.org/10.1136/annrheumdis-2017-eular.3961.CrossRef

41.

• Barker DJ, Maccari G, Georgiou X, Cooper MA, Flicek P, Robinson J, et al. The IPD-IMGT/HLA database. Nucleic Acids Res. 2023;51(D1):D1053–60. https://doi.org/10.1093/nar/gkac1011. (The IPD-IMGT/HLA database provides data for genes located within the human MHC region.)CrossRefPubMed

42.

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. https://doi.org/10.1007/s11926-017-0640-1.CrossRefPubMed

43.

Khan MA, Mathieu A, Sorrentino R, Akkoc N. The pathogenetic role of HLA-B27 and its subtypes. Autoimmun Rev. 2007;6(3):183–9. https://doi.org/10.1016/j.autrev.2006.11.003.CrossRefPubMed

44.

Sorrentino R, Bockmann RA, Fiorillo MT. HLA-B27 and antigen presentation: at the crossroads between immune defense and autoimmunity. Mol Immunol. 2014;57(1):22–7. https://doi.org/10.1016/j.molimm.2013.06.017.CrossRefPubMed

45.

Tedeschi V, Alba J, Paladini F, Paroli M, Cauli A, Mathieu A, et al. Unusual placement of an EBV epitope into the groove of the ankylosing spondylitis-associated HLA-B27 allele allows CD8+ T cell activation. Cells. 2019;8(6):572. https://doi.org/10.3390/cells8060572.CrossRefPubMedPubMedCentral

46.

Jah N, Jobart-Malfait A, Ermoza K, Noteuil A, Chiocchia G, Breban M, et al. HLA-B27 subtypes predisposing to ankylosing spondylitis accumulate in an endoplasmic reticulum-derived compartment apart from the peptide-loading complex. Arthritis Rheumatol. 2020;72(9):1534–46. https://doi.org/10.1002/art.41281.CrossRefPubMed

47.

Bowness P. HLA-B27. Annu Rev Immunol. 2015;33(1):29–48. https://doi.org/10.1146/annurev-immunol-032414-112110.CrossRefPubMed

48.

Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374(26):2563–74. https://doi.org/10.1056/NEJMra1406182.CrossRefPubMed

49.

Lim Kam Sian TCC, Indumathy S, Halim H, Greule A, Cryle MJ, Bowness P, et al. Allelic association with ankylosing spondylitis fails to correlate with human leukocyte antigen B27 homodimer formation. J Biol Chem. 2019;294(52):20185–95. https://doi.org/10.1074/jbc.RA119.010257.CrossRefPubMedPubMedCentral

50.

Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell. 1990;63(5):1099–112. https://doi.org/10.1016/0092-8674(90)90512-d.CrossRefPubMed

51.

Benjamin R, Parham P. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today. 1990;11(4):137–42. https://doi.org/10.1016/0167-5699(90)90051-a.CrossRefPubMed

52.

Feltkamp TE, Khan MA, Lopez de Castro JA. The pathogenetic role of HLA-B27. Immunol Today. 1996;17(1):5–7. https://doi.org/10.1016/0167-5699(96)80559-7.CrossRefPubMed

53.

Madden DR, Gorga JC, Strominger JL, Wiley DC. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell. 1992;70(6):1035–48. https://doi.org/10.1016/0092-8674(92)90252-8.CrossRefPubMed

54.

Welcome Trust Case Control Consortium; Australo-Anglo-American Spondylitis Consortium (TASC); Burton PR, Clayton DG, Cardon LR, 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(11):1329–37. https://doi.org/10.1038/ng.2007.17.

55.

International Genetics of Ankylosing Spondylitis Consortium (IGAS); Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, Leo P, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet. 2013;45(7):730–8. https://doi.org/10.1038/ng.2667

56.

Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, et al. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nat Genet. 2016;48(5):510–8. https://doi.org/10.1038/ng.3528.CrossRefPubMedPubMedCentral

57.

Li Z, Akar S, Yarkan H, Lee SK, Çetin P, Can G, et al. Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. PLoS Genet. 2019;15(4):e1008038. https://doi.org/10.1371/journal.pgen.1008038.CrossRefPubMedPubMedCentral

58.

• Garrido-Mesa J, Brown MA. T cell repertoire profiling and the mechanism by which HLA-B27 causes ankylosing spondylitis. Curr Rheumatol Rep. 2022;24(12):398–410. https://doi.org/10.1007/s11926-022-01090-6. (A good review explaining that AS is driven by the presentation of antigenic peptides to the adaptive immune system by HLA-B*27.)CrossRefPubMedPubMedCentral

59.

Wordsworth BP, Cohen CJ, Davidson C, Vecellio M. Perspectives on the genetic associations of ankylosing spondylitis. Front Immunol. 2021;12:603726. https://doi.org/10.3389/fimmu.2021.603726.CrossRefPubMedPubMedCentral

60.

Fatica M, D’Antonio A, Novelli L, Triggianese P, Conigliaro P, Greco E, et al. How has molecular biology enhanced our undertaking of axSpA and its management. Curr Rheumatol Rep. 2023;25(1):12–33. https://doi.org/10.1007/s11926-022-01092-4.CrossRefPubMed

61.

Liao HT, Tsai CY, Lai CC, Hsieh SC, Sun YS, Li KJ, et al. The potential role of genetics, environmental factors, and gut dysbiosis in the aberrant non-coding RNA expression to mediate inflammation and osteoclastogenic/osteogenic differentiation in ankylosing spondylitis. Front Cell Dev Biol. 2022;20(9):748063. https://doi.org/10.3389/fcell.2021.748063.CrossRef

62.

ENCODE Project Consortium; Snyder MP, Gingeras TR, Moore JE, Weng Z, Gerstein MB, Ren B, Perspectives on ENCODE. Nature. 2020;583(7818):693–698. https://doi.org/10.1038/s41586-020-2449-8. Epub 2020 Jul 29. Erratum in: Nature. 2022 May;605(7909):E4.

63.

•• Brown AC, Cohen CJ, Mielczarek O, Migliorini G, Costantino F, Allcock A, et al. Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis. Cell Genom. 2023;3(6):100306. https://doi.org/10.1016/j.xgen.2023.100306. (These investigators have provided comprehensive transcriptomic and epigenomic mapping in AS.)CrossRefPubMedPubMedCentral

64.

York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8–9 residues. Nat Immunol. 2002;3(12):1177–84. https://doi.org/10.1038/ni860.CrossRefPubMed

65.

Lopez de Castro JA, Alvarez-Navarro C, Brito A, Guasp P, Martin-Esteban A, Sanz-Bravo A. Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC-I-associated inflammatory disorders: towards a unifying view. Mol Immunol. 2016;77:193–204. https://doi.org/10.1016/j.molimm.2016.08.005.CrossRefPubMed

66.

Tsui FW, Haroon N, Reveille JD, Rahman P, Chiu B, Tsui HW, Inman RD. Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis. Ann Rheum Dis. 2010;69(4):733–6. https://doi.org/10.1136/ard.2008.103804.CrossRefPubMed

67.

Evans DM, Spencer CC, Pointon JJ, 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(8):761–7. https://doi.org/10.1038/ng.873.CrossRefPubMedPubMedCentral

68.

Robinson PC, Costello ME, Leo P, Bradbury LA, Hollis K, Cortes A, et al. ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients. Ann Rheum Dis. 2015;74(8):1627–9. https://doi.org/10.1136/annrheumdis-2015-207416.CrossRefPubMed

69.

Saulle I, Vicentini C, Clerici M, Biasin M. An overview on ERAP roles in infectious diseases. Cells. 2020;9(3). https://doi.org/10.3390/cells9030720

70.

Yao Y, Liu N, Zhou Z, Shi L. Influence of ERAP1 and ERAP2 gene polymorphisms on disease susceptibility in different populations. Hum Immunol. 2019;80(5):325–34. https://doi.org/10.1016/j.humimm.2019.02.011.CrossRefPubMed

71.

Klunk J, Vilgalys TP, Demeure CE, Cheng X, Shiratori M, Madej J, et al. Evolution of immune genes is associated with the Black Death. Nature. 2022;611(7935):312–9. https://doi.org/10.1038/s41586-022-05349-x.

72.

Barton AR, Santander CG, Skoglund P, Moltke I, Reich D, Mathieson I. Insufficient evidence for natural selection associated with the Black Death. bioRxiv. 2023;15:2023.03.14.532615. https://doi.org/10.1101/2023.03.14.532615.

73.

Lorente E, Fontela MG, Barnea E, Martín-Galiano AJ, Mir C, Galocha B, et al. Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2). Mol Cell Proteomics. 2020;19(6):994–1004. https://doi.org/10.1074/mcp.RA120.002014.CrossRefPubMedPubMedCentral

74.

Reveille JD, Zhou X, Lee M, Weisman MH, Yi L, Gensler LS, et al. HLA class I and II alleles in susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2019;78(1):66–73. https://doi.org/10.1136/annrheumdis-2018-213779.CrossRefPubMed

75.

Robinson WP, van der Linden SM, Khan MA, Rentsch HU, Cats A, Russell A, et al. HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27+ patients. Arthritis Rheum. 1989;32(9):1135–41. https://doi.org/10.1002/anr.1780320912.CrossRefPubMed

76.

Khan MA, Kushner I, Braun WE. B27-negative HLA-BW16 in ankylosing spondylitis. Lancet. 1978;1(8078):1370–1. https://doi.org/10.1016/s0140-6736(78)92455-8.CrossRefPubMed

77.

Khan MA, Kushner I, Braun WE. Association of HLA-A2 with uveitis in HLA-B27 positive patients with ankylosing spondylitis. J Rheumatol. 1981;8(2):295–8.PubMed

78.

Asquith M, Sternes PR, Costello ME, Karstens L, Diamond S, Martin TM, et al. HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome. Arthritis Rheumatol. 2019;71(10):1642–50. https://doi.org/10.1002/art.40917.CrossRefPubMed

79.

Berland M, Meslier V, Berreira Ibraim S, Le Chatelier E, Pons N, Maziers N, et al. Both disease activity and HLA-B27 status are associated with gut microbiome dysbiosis in spondyloarthritis patients. Arthritis Rheumatol. 2023;75(1):41–52. https://doi.org/10.1002/art.42289.CrossRefPubMed

80.

So J, Tam LS. Gut microbiome and its interaction with immune system in spondyloarthritis. Microorganisms. 2020;8(11). https://doi.org/10.3390/microorganisms8111727

81.

Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18(7):1069–76. https://doi.org/10.1038/nm.2817.CrossRefPubMed

82.

Gracey E, Yao Y, Green B, Qaiyum Z, Baglaenko Y, Lin A, et al. Sexual dimorphism in the Th17 signature of ankylosing spondylitis. Arthritis Rheumatol. 2016;68(3):679–89. https://doi.org/10.1002/art.39464.CrossRefPubMed

83.

Loll B, Fabian H, Huser H, Hee CS, Ziegler A, Uchanska-Ziegler B, et al. Increased conformational flexibility of HLA-B*27 subtypes associated with ankylosing spondylitis. Arthritis Rheumatol. 2016;68(5):1172–82. https://doi.org/10.1002/art.39567.CrossRefPubMed

84.

Loll B, Rückert C, Uchanska-Ziegler B, Ziegler A. Conformational plasticity of HLA-B27 molecules correlates inversely with efficiency of negative T cell selection. Front Immunol. 2020;11:179. https://doi.org/10.3389/fimmu.2020.00179.CrossRefPubMedPubMedCentral

85.

Faham M, Carlton V, Moorhead M, Zheng J, Klinger M, Pepin F, et al. Discovery of T cell receptor β motifs specific to HLA-B27-positive ankylosing spondylitis by deep repertoire sequence analysis. Arthritis Rheumatol. 2017;69(4):774–84. https://doi.org/10.1002/art.40028.CrossRefPubMed

86.

Huang H, Sikora MJ, Islam S, Chowdhury RR, Chien YH, Scriba TJ, et al. Select sequencing of clonally expanded CD8(+) T cells reveals limits to clonal expansion. Proc Natl Acad Sci U S A. 2019;116(18):8995–9001. https://doi.org/10.1073/pnas.1902649116.CrossRefPubMedPubMedCentral

87.

Zheng M, Zhang X, Zhou Y, Tang J, Han Q, Zhang Y, et al. TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in ankylosing spondylitis. EBioMedicine. 2019;47:414–26. https://doi.org/10.1016/j.ebiom.2019.07.032.CrossRefPubMedPubMedCentral

88.

Hanson AL, Nel HJ, Bradbury L, Phipps J, Thomas R, Lê Cao KA, et al. Altered repertoire diversity and disease-associated clonal expansions revealed by T cell receptor immunosequencing in ankylosing spondylitis patients. Arthritis Rheumatol. 2020;72(8):1289–302. https://doi.org/10.1002/art.41252.CrossRefPubMed

89.

Komech EA, Koltakova AD, Barinova AA, Minervina AA, Salnikova MA, Shmidt EI, et al. TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis. Front Immunol. 2022;13:973243. https://doi.org/10.3389/fimmu.2022.973243.CrossRefPubMedPubMedCentral

90.

•• Yang X, Garner LI, Zvyagin IV, Paley MA, Komech EA, Jude KM, et al. Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides. Nature. 2022;612(7941):771–7. (HLA-B*27:05-presented microbial peptides act as a trigger for autoimmunity by activating CD8+ T cells that cross-react with self-peptides and result in AS, virtually solving the 50-year-old puzzle of how HLA-B*27 leads to disease.)CrossRefPubMedPubMedCentral

91.

• Zhai Y, Chen L, Zhao Q, Zheng ZH, Chen ZN, Bian H, et al. Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity. Science. 2023;379(6637):eabg2482. https://doi.org/10.1126/science.abg2482. (This study reports that autoimmunity in patients with AS results from neoantigens formed by post-translational modification of proteins that break immune tolerance.)

92.

Law SC, Street S, Yu CH, Capini C, Ramnoruth S, Nel HJ, et al. T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles. Arthritis Res Ther. 2012;14(3):R118. https://doi.org/10.1186/ar3848.CrossRefPubMedPubMedCentral

93.

Khan MA, Khan MK. Diagnostic value of HLA-B27 testing ankylosing spondylitis and Reiter’s syndrome. Ann Intern Med. 1982;96(1):70–6. https://doi.org/10.7326/0003-4819-96-1-70.CrossRefPubMed

94.

Khan MA, Haroon M, Rosenbaum JT. Acute anterior uveitis and spondyloarthritis: more than meets the eye. Curr Rheumatol Rep. 2015;17(9):59. https://doi.org/10.1007/s11926-015-0536-x.CrossRefPubMed

95.

Standardization of Uveitis Nomenclature (SUN) Working Group.Classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis. Am J Ophthalmol. 2021;228:117–25. https://doi.org/10.1016/j.ajo.2021.03.049.

96.

Ozgocmen S, Khan MA. Current concept of spondyloarthritis: special emphasis on early referral and diagnosis. Curr Rheumatol Rep. 2012;14(5):409–14. https://doi.org/10.1007/s11926-012-0274-2.CrossRefPubMed

97.

Navarro-Compán V, Benavent D, Capelusnik D, van der Heijde D, Landewé RB, Poddubnyy D, et al. ASAS consensus definition of early axial spondyloarthritis. Ann Rheum Dis. 2023. https://doi.org/10.1136/ard-2023-224232.CrossRefPubMed

98.

Brown MA, Li Z, Cao KL. Biomarker development for axial spondyloarthritis. Nat Rev Rheumatol. 2020;16(8):448–63. https://doi.org/10.1038/s41584-020-0450-0.CrossRefPubMed

99.

Prajzlerova K, Grobelna K, Pavelka K, Senolt L, Filkova M. An update on biomarkers in axial spondyloarthritis. Autoimmun Rev. 2016;15(6):501–9. https://doi.org/10.1016/j.autrev.2016.02.002.CrossRefPubMed

100.

Maksymowych WP. Biomarkers for diagnosis of axial spondyloarthritis, disease activity, prognosis, and prediction of response to therapy. Front Immunol. 2019;10:305. https://doi.org/10.3389/fimmu.2019.00305.CrossRefPubMedPubMedCentral

101.

Liu S, Ji W, Lu J, Tang X, Guo Y, Ji M, et al. Discovery of potential serum protein biomarkers in ankylosing spondylitis using tandem mass tag-based quantitative proteomics. J Proteome Res. 2020;19(2):864–72. https://doi.org/10.1021/acs.jproteome.9b00676.CrossRefPubMed

102.

Li H, Wang L, Zhu J, Xiao J, Yang H, Hai H, et al. Diagnostic serum biomarkers associated with ankylosing spondylitis. Clin Exp Med. 2023;23(5):1729–39. https://doi.org/10.1007/s10238-022-00958-2.CrossRefPubMed

103.

Jarlborg M, Courvoisier DS, Lamacchia C, Martinez Prat L, Mahler M, Bentow C, et al. Serum calprotectin: a promising biomarker in rheumatoid arthritis and axial spondyloarthritis. Arthritis Res Ther. 2020;22(1):105. https://doi.org/10.1186/s13075-020-02190-3.CrossRefPubMedPubMedCentral

104.

De Craemer AS, Witte T, Lobaton Ortega T, Hoorens A, De Vos M, Cuvelier C, et al. Anti-CD74 IgA antibodies show diagnostic potential for axial spondyloarthritis but are not associated with microscopic gut inflammation. Rheumatology (Oxford). 2023;62(2):984–90. https://doi.org/10.1093/rheumatology/keac384.CrossRefPubMed

105.

Li D, Cao R, Dong W, Cheng M, Pan X, Hu Z, et al. Identification of potential biomarkers for ankylosing spondylitis based on bioinformatics analysis. BMC Musculoskelet Disord. 2023;24(1):413. https://doi.org/10.1186/s12891-023-06550-3.CrossRefPubMedPubMedCentral

106.

Hwang M, Assassi S, Zheng J, Castillo J, Chavez R, Vanarsa K, et al. Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis. Arthritis Res Ther. 2023;25(1):57. https://doi.org/10.1186/s13075-023-03044-4.CrossRefPubMedPubMedCentral

107.

•• Pupeza I, Huber M, Trubetskov M, Schweinberger W, Hussain SA, Hofer C, et al. Field-resolved infrared spectroscopy of biological systems. Nature. 2020;577(7788):52–9. https://doi.org/10.1038/s41586-019-1850-7. (The senior author of this paper—Ferenc Krauz—has just been awarded the 2023 Nobel Prize in Physics for his role in the discovery of this new technology.)CrossRefPubMed

108.

• Eissa T, Kepesidis KV, Zigman M, Huber M. Limits and prospects of molecular fingerprinting for phenotyping biological systems revealed through in silico modeling. Anal Chem. 2023;95(16):6523–32. https://doi.org/10.1021/acs.analchem.2c04711. (The authors describe the potential benefits of their newly developed technologies in health diagnostics.)CrossRefPubMedPubMedCentral

109.

Brown MA, Aletaha D. Genetic risk scores in inflammatory arthritis: a new era? Nat Rev Rheumatol. 2020;16(10):545–6. https://doi.org/10.1038/s41584-020-0473-6.CrossRefPubMed

110.

Li Z, Wu X, Leo PJ, De Guzman E, Akkoc N, Breban M, et al. Polygenic risk scores have high diagnostic capacity in ankylosing spondylitis. Ann Rheum Dis. 2021;80(9):1168–74. https://doi.org/10.1136/annrheumdis-2020-219446.CrossRefPubMed

111.

Huang XF, Li Z, De Guzman E, Robinson P, Gensler L, Ward MM, et al. Genomewide association study of acute anterior uveitis identifies new susceptibility loci. Invest Ophthalmol Vis Sci. 2020;61(6):3. https://doi.org/10.1167/iovs.61.6.3.CrossRefPubMedPubMedCentral

112.

Robinson PC, Claushuis TA, Cortes A, Martin TM, Evans DM, Leo P, et al. Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol. 2015;67(1):140–51. https://doi.org/10.1002/art.38873.CrossRefPubMedPubMedCentral

113.

Ramaswami R, Bayer R, Galea S. Precision medicine from a public health perspective. Annu Rev Public Health. 2018;39:153–68. https://doi.org/10.1146/annurev-publhealth-040617-014158.CrossRefPubMed

114.

• Allard-Chamard H, Li Q, Rahman P. Emerging concepts in precision medicine in axial spondyloarthritis. Curr Rheumatol Rep. 2023;25(10):204–12. https://doi.org/10.1007/s11926-023-01113-w. (A good review on precision medicine in axSpA.)CrossRefPubMed

115.

Khan MA, Kushner I, Braun WE, Zachary AA, Steinberg AG. HLA-B27 homozygosity in ankylosing spondylitis: relationship to risk and severity. Tissue Antigens. 1978;11(5):434–8. https://doi.org/10.1111/j.1399-0039.1978.tb01280.x.CrossRefPubMed

116.

Jaakkola E, Herzberg I, Laiho K, Barnardo MC, Pointon JJ, Kauppi M, et al. Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis. Ann Rheum Dis. 2006;65(6):775–80. https://doi.org/10.1136/ard.2005.041103.CrossRefPubMed

117.

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(4):574–9.PubMed

118.

Morin M, Hellgren K, Frisell T. Familial aggregation and heritability of ankylosing spondylitis - a Swedish nested case-control study. Rheumatology (Oxford). 2020;59(7):1695–702. https://doi.org/10.1093/rheumatology/kez519.CrossRefPubMed

119.

•• van der Linden SM, Khan MA, Li Z, Baumberger H, Zandwijk HV, Khan MK, et al. Recurrence of axial spondyloarthritis among first-degree relatives in a prospective 35-year-follow-up family study. RMD Open. 2022;8(2). https://doi.org/10.1136/rmdopen-2022-002208. (This prospective family study of 125 Swiss AS probands and their 360 first-degree relatives found that axSpA developed in 27.1% of HLA-B27(+) FDR after 35 years of follow-up.)

120.

• van der Linden SM, Khan MA, Li Z, Baumberger H, Zandwijk HV, Khan K, et al. Factors predicting axial spondyloarthritis among first-degree relatives of probands with ankylosing spondylitis: a family study spanning 35 years. Ann Rheum Dis. 2022;81(6):831–7. https://doi.org/10.1136/annrheumdis-2021-222083. (A “3-Region Index” that defines “chronic inflammatory axial spinal pain” is a much better predictor of the occurrence of axSpA than chronic inflammatory back pain.)CrossRefPubMed

121.

Chen S, Li Z, Chen D, Cui H, Wang J, Li Z, Li X, Zheng Z, Zhan Z, Liu H. Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis. Ann Rheum Dis. 2023;82(4):533–45. https://doi.org/10.1136/ard-2022-223428.CrossRefPubMed

122.

Mauro D, Thomas R, Guggino G, Lories R, Brown MA, Ciccia F. Ankylosing spondylitis: an autoimmune or autoinflammatory disease? Nat Rev Rheumatol. 2021;17(7):387–404. https://doi.org/10.1038/s41584-021-00625-y.CrossRefPubMed

123.

Watad A, Cuthbert RJ, Amital H, McGonagle D. Enthesitis: much more than focal insertion point inflammation. Curr Rheumatol Rep. 2018;20(7):41. https://doi.org/10.1007/s11926-018-0751-3.CrossRefPubMedPubMedCentral

124.

• Nam B, Jo S, Bang SY, Park Y, Shin JH, Park YS, et al. Clinical and genetic factors associated with radiographic damage in patients with ankylosing spondylitis. Ann Rheum Dis. 2023;82(4):527–32. https://doi.org/10.1136/ard-2022-222796. (This is a GWAS study to identify clinical and genetic factors associated with severe radiographic damage in AS.)CrossRefPubMed

125.

Nancy Z, Yan L, Hui S, Paul B, Liye C. From the genetics of ankylosing spondylitis to new biology and drug target discovery. Front Immunol. 2021;17(12):624632. https://doi.org/10.3389/fimmu.2021.624632.CrossRef

126.

Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599–613. https://doi.org/10.1002/art.41042.CrossRefPubMedPubMedCentral

127.

Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2023;82(1):19–34. https://doi.org/10.1136/ard-2022-223296.CrossRefPubMed

128.

Akkoc N, Khan MA. JAK inhibitors for axial spondyloarthritis: what does the future hold? Curr Rheumatol Rep. 2021;23(6):34. https://doi.org/10.1007/s11926-021-01001-1.CrossRefPubMed

129.

Baraliakos X, van der Heijde D, Sieper J, Inman RD, Kameda H, Li Y, et al. Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study. Arthritis Res Ther. 2023;25(1):172. https://doi.org/10.1186/s13075-023-03128-1.CrossRefPubMedPubMedCentral

130.

Danve A, Deodhar A. Treatment of axial spondyloarthritis: an update. Nat Rev Rheumatol. 2022;18(4):205–16. https://doi.org/10.1038/s41584-022-00761-z.CrossRefPubMed

131.

Armaka M, Apostolaki M, Jacques P, Kontoyiannis DL, Elewaut D, Kollias G. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med. 2008;205(2):331–7. https://doi.org/10.1084/jem.20070906.CrossRefPubMedPubMedCentral

132.

• Tavasolian F, Inman RD. Biology and therapeutic potential of mesenchymal stem cell extracellular vesicles in axial spondyloarthritis. Commun Biol. 2023;6(1):413. https://doi.org/10.1038/s42003-023-04743-z. (A current review on the therapeutic potential of mesenchymal stem cells in axSpA.)CrossRefPubMedPubMedCentral

133.

Jans LBO, Chen M, Elewaut D, Van den Bosch F, Carron P, Jacques P, et al. MRI-based synthetic CT in the detection of structural lesions in patients with suspected sacroiliitis: comparison with MRI. Radiology. 2021;298(2):343–9. https://doi.org/10.1148/radiol.2020201537.CrossRefPubMed

134.

Fritz J, Kijowski R, Recht MP. Artificial intelligence in musculoskeletal imaging: a perspective on value propositions, clinical use, and obstacles. Skeletal Radiol. 2022;51(2):239–43. https://doi.org/10.1007/s00256-021-03802-y.CrossRefPubMed

135.

Diekhoff T, Hermann KGA, Lambert RG. Future of low-dose computed tomography and dual-energy computed tomography in axial spondyloarthritis. Curr Rheumatol Rep. 2022;24(6):198–205. https://doi.org/10.1007/s11926-022-01075-5.CrossRefPubMedPubMedCentral

136.

Van Den Berghe T, Babin D, Chen M, Callens M, Brack D, Maes H, et al. Neural network algorithm for detection of erosions and ankylosis on CT of the sacroiliac joints: multicentre development and validation of diagnostic accuracy. Eur Radiol. 2023. https://doi.org/10.1007/s00330-023-09704-y.CrossRefPubMed

137.

Khan MA, Khan MK, Kushner I. Survival among patients with ankylosing spondylitis: a life-table analysis. J Rheumatol. 1981;8(1):86–90.PubMed

138.

•• Li Z, Khan MK, van der Linden S, Villiger PM, Baumberger H, van Zandwijk H, Khan MA, Brown MA. HLA-B*27, axial spondyloarthritis, and survival. Ann Rheum Dis. 2023; Sept 7. https://doi.org/10.1136/ard-2023-224434. (HLA-B*27(+) patients with AS have reduced life expectancy. But HLA-B*27(+) individuals in the general population have a normal lifespan.)

139.

• Braun J, Sieper J. Fifty years after the discovery of the association of HLA B27 with ankylosing spondylitis. RMD Open. 2023;9(3):e003102. https://doi.org/10.1136/rmdopen-2023-003102. (A nice and concise review on this subject.)CrossRefPubMedPubMedCentral

140.

•• Britanova OV, Lupyr KR, Staroveros DB, Shagina IA, Somov DV, Klimenko A, et al. Targeted depletion of TRBV+ T cell as immunotheraphy in a ptient with ankylosing spondylitis. Nat Med. 2023. https://doi.org/10.1038/s41591-023-02613-z. The first report of dramatic efficacy of targeted depletion of TRBV9+ T cells as immunotherapy in an HLA-B*27(+) patient with ankylosing spondylitis has just been published.

Titel: HLA-B*27 and Ankylosing Spondylitis: 50 Years of Insights and Discoveries
verfasst von: Muhammad A. Khan
Publikationsdatum: 11.11.2023
Verlag: Springer US
Erschienen in: Current Rheumatology Reports / Ausgabe 12/2023
Print ISSN: 1523-3774
Elektronische ISSN: 1534-6307
DOI: https://doi.org/10.1007/s11926-023-01118-5

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2023

Possible Role of Dysbiosis of the Gut Microbiome in SLE

How to Use Janus Kinase Inhibitors in the Treatment of Rheumatoid Arthritis? A Clinical Assessment of Risks and Benefits

The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects

The Role of Environmental Factors in the Development of Idiopathic Inflammatory Myopathies: a Narrative Review

A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition, Clinical Presentation, and Management