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Review Article

HLA-B27 Anterior Uveitis: Immunology and Immunopathology

, MD, , MD, , MBBS & , MD
Pages 450-459 | Received 06 Jan 2016, Accepted 18 Feb 2016, Published online: 31 May 2016

REFERENCES

  • Wakefield D, Chang JH, Amjadi S, et al. What is new HLA-B27 acute anterior uveitis? Ocul Immunol Inflamm. 2011;19:139–144.
  • Wakefield D, Chang JH. Epidemiology of uveitis. Int Ophthalmol Clin. 2005;45:1–13.
  • Chang JH, Wakefield D. Uveitis: a global perspective. Ocul Immunol Inflamm. 2002;10:263–279.
  • Karaconji T, Maconochie Z, McCluskey P. Acute anterior uveitis in Sydney. Ocul Immunol Inflamm. 2013;21:108–114.
  • Robinson PC, Benham H. Advances in classification, basic mechanisms and clinical science in ankylosing spondylitis and axial spondyloarthritis. Intern Med J. 2015;45:127–133.
  • Robinson PC, Claushuis TA, Cortes A, et al. Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol. 2015;67:140–151.
  • Hou S, Kijlstra A, Yang P. Molecular genetic advances in uveitis. Prog Mol Biol Transl Sci. 2015;134:283–298.
  • Khan MA, Haroon M, Rosenbaum JT. Acute anterior uveitis and spondyloarthritis: more than meets the eye. Curr Rheumatol Rep. 2015;17:536.
  • Derhaag PJ, Linssen A, Broekema N, et al. A familial study of the inheritance of HLA-B27-positive acute anterior uveitis. Am J Ophthalmol. 1988;105:603–606.
  • Khan MA, Kushner I, Braun WE. Association of HLA-A2 with uveitis in HLA-B27 positive patients with ankylosing spondylitis. J Rheumatol. 1981;8:295–298.
  • Loukil H, Kamoun A, Mahfoudh N, et al. Association study of MICA-TM and HLA-class I polymorphism with uveitis in South Tunisian population. Pathol Biol (Paris). 2015;63:101–105.
  • Goto K, Ota M, Maksymowych WP, et al. Association between MICA gene A4 allele and acute anterior uveitis in white patients with and without HLA-B27. Am J Ophthalmol. 1998;126:436–441.
  • Lindner E, Steinwender G, Plainer S, et al. Role of IL-10 gene polymorphisms in intermediate and HLA-B27-associated uveitis. Acta Ophthalmol (Copenh). 2013;91:e415–e417.
  • Wakefield D, Buckley R, Golding J, et al. Association of complement allotype C4B2 with anterior uveitis. Hum Immunol. 1988;21:233–237.
  • Yang MM, Lai TY, Tam PO, et al. CFH 184G as a genetic risk marker for anterior uveitis in Chinese females. Mol Vis. 2011;17:2655–2664.
  • Yang MM, Lai TY, Tam PO, et al. Association of C2 and CFB polymorphisms with anterior uveitis. Invest Ophthalmol Vis Sci. 2012;53:4969–4974.
  • Yang MM, Lai TY, Tam PO, et al. Association of CFH and SERPING1 polymorphisms with anterior uveitis. Br J Ophthalmol. 2013;97:1475–1480.
  • Xiang Q, Chen L, Fang J, et al. TNF receptor-associated factor 5 gene confers genetic predisposition to acute anterior uveitis and pediatric uveitis. Arthritis Res Ther. 2013;15:R113.
  • El-Shabrawi Y, Wegscheider BJ, Weger M, et al. Polymorphisms within the tumor necrosis factor-alpha promoter region in patients with HLA-B27-associated uveitis: association with susceptibility and clinical manifestations. Ophthalmology. 2006;113:695–700.
  • Levinson RD. Killer immunoglobulin-like receptor genes in uveitis. Ocul Immunol Inflamm. 2011;19:192–201.
  • Singleton EM, Hutson SE. Anterior uveitis, inflammatory bowel disease, and ankylosing spondylitis in a HLA-B27-positive woman. South Med J. 2006;99:531–533.
  • Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–1463.
  • Chang JH, McCluskey PJ, Wakefield D. Recent advances in Toll-like receptors and anterior uveitis. Clin Experiment Ophthalmol. 2012;40:821–828.
  • Pratap DS, Lim LL, Wang JJ, et al. The role of toll-like receptor variants in acute anterior uveitis. Mol Vis. 2011;17:2970–2977.
  • Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or assistants? J Leukoc Biol. 2010;87:989–999.
  • Chang JH, Hampartzoumian T, Everett B, et al. Changes in toll-like receptor (TLR)-2 and TLR4 expression and function but not polymorphisms are associated with acute anterior uveitis. Invest Ophthalmol Vis Sci. 2007;48:1711–1717.
  • Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. results of the first international workshop. Am J Ophthalmol. 2005;140:509–516.
  • Wakefield D, Montanaro A, McCluskey P. Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 1991;36:223–232.
  • Chang JH, McCluskey PJ, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 2005;50:364–388.
  • Paiva ES, Macaluso DC, Edwards A, et al. Characterisation of uveitis in patients with psoriatic arthritis. Ann Rheum Dis. 2000;59:67–70.
  • Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015. Recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2015;68:282–298.
  • Martin TM, Rosenbaum JT. An update on the genetics of HLA B27-associated acute anterior uveitis. Ocul Immunol Inflamm. 2011;19:108–114.
  • Benjamin R, Parham P. Guilt by association: HLA B27 and ankylosing spondylitis. Immunol Today. 1990;11:137–142.
  • Ramos M, López de Castro JA. HLA-B27 and the pathogenesis of spondyloarthritis. Tissue Antigens. 2002;60:191–205.
  • Smith JA, Märker-Hermann E, Colbert RA. Pathogenesis of ankylosing spondylitis: current concepts. Best Pract Res Clin Rheumatol. 2006;20:571–591.
  • Hermann E, Meyer zum Büschenfelde KH, Fleischer B, et al. HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis. Lancet. 1993;342:646–650.
  • Ugrinovic S, Mertz A, Wu P, et al. 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;159:5715–5723.
  • Scofield RH, Kurien B, Gross T, et al. HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies. Lancet. 1995;345:1542–1544.
  • Frauendorf E, Von Goessel H, May E, et al. HLA-B27-restricted T cells from patients with ankylosing spondylitis recognize peptides from B*2705 that are similar to bacteria-derived peptides. Clin Exp Immunol. 2003;134:351–359.
  • Kuon W, Holzhutter H-G, 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;167:4738–4746.
  • 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;6:1–14.
  • Mattila L, Salminen L, Terho P. Chlamydial immunofluorescence serology in anterior uveitis. Br J Ophthalmol. 1982;66:654–657.
  • Wakefield D, Penny R. Cell-mediated immune response to chlamydia in anterior uveitis: role of HLA B27. Clin Exp Immunol. 1983;51:191–196.
  • Wakefield D, Robinson P, Easter J, et al. Decreased chemiluminescent associated phagocytic response of peripheral blood mononuclear cells to Chlamydia trachomatis in patients with HLA-B27+ anterior uveitis. Rheumatology. 1985;24:332–339.
  • Huhtinen M, Laasila K, Granfors K, et al. Infectious background of patients with a history of acute anterior uveitis. Ann Rheum Dis. 2002;61:1012–1016.
  • Otasevic L, Walduck A, Meyer TF, et al. Helicobacter pylori infection in anterior uveitis. Infection. 2005;33:82–85.
  • Otasevic L, Zlatanovic G, Stanojevic-Paovic A, et al. Helicobacter pylori: an underestimated factor in acute anterior uveitis and spondyloarthropathies? Ophthalmologica. 2007;221:6–13.
  • Madden D, Gorga J, Strominger J, et al. The structure of HLA B27 reveals nonamer self-peptides bound in an extended conformation. Nature. 1991;353:321–325.
  • Madden DR, Gorga JC, Strominger JL, et al. The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC. Cell. 1992;70:1035–1048.
  • Khan M. Polymorphism of HLA-B27: 105 subtypes currently known. Curr Rheumatol Rep. 2013;15:1–6.
  • Robinson J, Halliwell JA, Hayhurst JD, et al. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2015;43:D423–D431.
  • D’Amato M, Fiorillo MT, Carcassi C, et al. Relevance of residue 116 of HLA-B27 in determining susceptibility to ankylosing spondylitis. Eur J Immunol. 1995;25:3199–3201.
  • López de Castro JA. HLA-B27 and the pathogenesis of spondyloarthropathies. Immunol Lett. 2007;108:27–33.
  • Jardetzky TS, Lane WS, Robinson RA, et al. Identification of self peptides bound to purified HLA-B27. Nature. 1991;353:326–329.
  • Urban R, Chicz R, Lane W, et al. A subset of HLA-B27 molecules contains peptides much longer than nonamers. Proc Natl Acad Sci USA. 1994;91:1534–1538.
  • Fiorillo MT, Meadows L, D’Amato M, et al. Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes. Eur J Immunol. 1997;27:368–373.
  • Stodůlková E, Pohl J, Man P, et al. Comparison of amino acid compositions of peptides eluted from HLA-B27 molecules of healthy individuals and patients with ankylosing spondylitis. Immunol Lett. 2006;103:135–141.
  • Alvarez-Navarro C, Cragnolini JJ, Dos Santos HG, et al. Novel HLA-B27-restricted epitopes from Chlamydia trachomatis generated upon endogenous processing of bacterial proteins suggest a role of molecular mimicry in reactive arthritis. J Biol Chem. 2013;288:25810–25825.
  • Schittenhelm RB, Sian TC, Wilmann PG, et al. Revisiting the arthritogenic peptide theory: quantitative not qualitative changes in the peptide repertoire of HLA-B27 allotypes. Arthritis Rheumatol. 2015;67:702–713.
  • 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;163:6665–6670.
  • Colbert RA. HLA-B27 misfolding: a solution to the spondyloarthropathy conundrum? Mol Med Today. 2000;6:224–230.
  • Schröder M, Kaufman RJ. ER stress and the unfolded protein response. Mut Res. 2005;569(1–2):29–63.
  • el-Zaatari F, Sams K, Taurog J. In vitro mutagenesis of HLA-B27. Amino acid substitutions at position 67 disrupt anti-B27 monoclonal antibody binding in direct relation to the size of the substituted side chain. J Immunol. 1990;144:1512–1517.
  • Appel H, Kuon W, Kuhne M, et al. The solvent-inaccessible Cys67 residue of HLA-B27 contributes to T cell recognition of HLA-B27/peptide complexes. J Immunol. 2004;173:6564–6573.
  • 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;173:1699–1710.
  • Kubagawa H, Chen CC, Ho LH, et al. Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B. J Exp Med. 1999;189:309–318.
  • Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition. Immunology. 2005;115:433–440.
  • Park HJ, Atkinson JP. Autoimmunity: homeostasis of innate immunity gone awry. J Clin Immunol. 2012;32:1148–1152.
  • McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3:e297.
  • Bi HS, Liu ZF, Cui Y. Pathogenesis of innate immunity and adaptive immunity in the mouse model of experimental autoimmune uveitis. J Chin Med Assoc. 2015;78:276–282.
  • Willermain F, Rosenbaum JT, Bodaghi B, et al. Interplay between innate and adaptive immunity in the development of non-infectious uveitis. Prog Retin Eye Res. 2012;31:182–194.
  • 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;170:1099–1105.
  • Taurog JD, Dorris ML, Satumtira N, et al. Spondylarthritis in HLA-B27/human beta2-microglobulin-transgenic rats is not prevented by lack of CD8. Arthritis Rheum. 2009;60:1977–1984.
  • Cauli A, Shaw J, Giles J, et al. The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09. Rheumatology (Oxford). 2013;52:1952–1962.
  • Jiao YL, Zhang BC, You L, et al. Polymorphisms of KIR gene and HLA-C alleles: possible association with susceptibility to HLA-B27-positive patients with ankylosing spondylitis. J Clin Immunol. 2010;30:840–844.
  • Levinson RD, Martin TM, Luo L, et al. Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy. Invest Ophthalmol Vis Sci. 2010;51:1505–1510.
  • Zvyagin IV, Mamedov IZ, Britanova OV, et al. Contribution of functional KIR3DL1 to ankylosing spondylitis. Cell Mol Immunol. 2010;7:471–476.
  • Vendelbosch S, Heslinga SC, John M, et al. Study on the protective effect of the KIR3DL1 gene in ankylosing spondylitis. Arthritis Rheumatol. 2015;67:2957–2965.
  • Hammer RE, Maika SD, Richardson JA, et al. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell. 1990;63:1099–1112.
  • Sheehan NJ. The ramifications of HLA-B27. J R Soc Med. 2004;97:10–14.
  • Taurog JD, Richardson JA, Croft JT, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994;180:2359–2364.
  • Rosenbaum JT, McDevitt HO, Guss RB, et al. Endotoxin-induced uveitis in rats as a model for human disease. Nature. 1980;286:611–613.
  • Sherlock JP, Buckley CD, Cua DJ. The critical role of interleukin-23 in spondyloarthropathy. Mol Immunol. 2014;57:38–43.
  • Benham H, Rehaume LM, Hasnain SZ, Velasco J, Baillet AC, Ruutu M, Kikly K, Wang R, Tseng HW, Thomas GP et al. Interleukin-23 mediates the intestinal response to microbial beta-1,3-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheumatol 2014;66(7):1755–1767.
  • Sherlock JP, Cua DJ. Interleukin-23: a promising therapeutic target in seronegative spondyloarthropathy. Curr Opin Pharmacol. 2013;13:445–448.
  • Kanski JJ. Anterior uveitis in juvenile rheumatoid arthritis. Arch Ophthalmol. 1977;95:1794–1797.
  • Bajwa A, Lee CS, Patrie J, et al. Clinical and visual outcomes of patients with uveitis in the mid-Atlantic United States. Clin Ophthalmol. 2015;9:1655–1664.
  • Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492–513.
  • Yates WB, Vajdic CM, Na R, et al. Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study. Ophthalmology. 2015;122:265–273.
  • Yates WB, McCluskey PJ, Wakefield D. Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy? J Ophthalmic Inflamm Infect. 2013;3:48.
  • Ooi KG, Galatowicz G, Calder VL, et al. Cytokines and chemokines in uveitis: is there a correlation with clinical phenotype? Clin Med Res. 2006;4:294–309.
  • Lacomba MS, Martin CM, Chamond RR, et al. Aqueous and serum interferon gamma, interleukin (IL) 2, IL-4, and IL-10 in patients with uveitis. Arch Ophthalmol. 2000;118:768–772.
  • Braun J, Baraliakos X, Listing J, et al. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005;52:2447–2451.
  • El-Shabrawi Y, Hermann J. Anti-tumor necrosis factor-alpha therapy with infliximab as an alternative to corticosteroids in the treatment of human leukocyte antigen B27-associated acute anterior uveitis. Ophthalmology. 2002;109:2342–2346.
  • van Denderen JC, Visman IM, Nurmohamed MT, et al. Adalimumab significantly reduces the recurrence rate of anterior uveitis in patients with ankylosing spondylitis. J Rheumatol. 2014;41:1843–1848.
  • Galor A, Perez VL, Hammel JP, et al. Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology. 2006;113:2317–2323.
  • Miserocchi E, Modorati G, Pontikaki I, et al. Long-term treatment with golimumab for severe uveitis. Ocul Immunol Inflamm. 2014;22:90–95.
  • Petropoulos IK, Vaudaux JD, Guex-Crosier Y. Anti-TNF-alpha therapy in patients with chronic non-infectious uveitis: the experience of Jules Gonin Eye Hospital. Klin Monbl Augenheilkd. 2008;225:457–461.
  • Salgado E, Gomez-Reino JJ. The risk of tuberculosis in patients treated with TNF antagonists. Expert Rev Clin Immunol. 2011;7:329–340.
  • Chung ES, Packer M, Lo KH, et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–3140.
  • Wendling D, Paccou J, Berthelot JM, et al. New onset of uveitis during anti-tumor necrosis factor treatment for rheumatic diseases. Semin Arthritis Rheum. 2011;41:503–510.
  • Lim L, Suhler EB, Smith JR. Biologic therapies for inflammatory eye disease. Clin Experiment Ophthalmol. 2006;34:365–374.
  • Thurau SR, Diedrichs-Mohring M, Fricke H, et al. Oral tolerance with an HLA-peptide mimicking retinal autoantigen as a treatment of autoimmune uveitis. Immunol Lett. 1999;68(2–3):205–212.
  • Thurau SR, Fricke H, Burchardi C, et al. Long-term follow-up of oral tolerance induction with HLA-peptide B27PD in patients with uveitis. Ann N Y Acad Sci. 2004;1029:408–412.
  • Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev. 2004;17:348–369.
  • Carter JD, Gerard HC, Whittum-Hudson JA, et al. Combination antibiotics for the treatment of Chlamydia-induced reactive arthritis: is a cure in sight? Int J Clin Rheumatol. 2011;6:333–345.
  • Kvien TK, Gaston JS, Bardin T, et al. Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study. Ann Rheum Dis. 2004;63:1113–1119.
  • Wakefield D, McCluskey P, Verma M, et al. Ciprofloxacin treatment does not influence course or relapse rate of reactive arthritis and anterior uveitis. Arthritis Rheum. 1999;42:1894–1897.
  • Frydén A, Bengtsson A, Foberg U, et al. Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study. BMJ. 1990;301:1299–1302.

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