The objective of this study is to investigate the relationship between clinical features of ankylosing spondylitis (AS) and HLA-B27 status or its subtypes. Clinical data and blood samples were collected with patients’ informed consent. Luminex liquid array combining polymerase chain reaction-sequence specific oligonucleotide probe was used to do the low-resolution HLA-B genotype typing. Polymerase chain reaction-sequence specific primer was applied to do the high resolution HLA-B27 typing. In 98 subjects, 93 were HLA-B27 positive, of which three subtypes were detected: B*2704 (n = 76), B*2705 (n = 12), and B*2715 (n = 5). The onset age for B27 negative and positive group was 28 ± 7.9 and 21.1 ± 6.2 years, respectively (χ2 = −2.047, P = 0.041). The onset age for B*2704, B*2705 and B*2715 group was 20.45 ± 4.50, 26.67 ± 9.95 and 17.8 ± 11.12 years, respectively (χ2 = 7.888, P = 0.019). No significant difference was found between B27 positive and negative group, or among three B27 subtypes groups for other clinical features. In conclusion, the clinical features of AS may be correlated with HLA-B27 status and its polymorphism.
Ankylosing spondylitis HLA-B27 Polymorphism
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This work was supported by Distinguished Young Scientist Research Grant (30325019) and National Natural Science Foundation of China Grant (30571735).
Conflict of interest statement
All the authors have no conflict of interest.
Blanco-Gelaz MA, Lopez-Vazquez A, Garcia-Fernandez S et al (2001) Genetic variability, molecular evolution, and geographic diversity of HLA-B27. Hum Immunol 62(9):1042–1050PubMedCrossRefGoogle Scholar
Sieper J, Rudwaleit M, Khan MA et al (2006) Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol 20(3):401–417PubMedCrossRefGoogle Scholar
Brown MA, Kennedy LG, MacGregor AJ et al (1997) Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum 40(10):1823–1828PubMedCrossRefGoogle Scholar
Sims AM, Barnardo M, Herzberg I et al (2007) Non-B27 MHC associations of ankylosing spondylitis. Genes Immun 8(2):115–123PubMedCrossRefGoogle Scholar
Laval SH, Timms A, Edwards S et al (2001) Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci. Am J Hum Genet 68(4):918–926PubMedCrossRefGoogle Scholar
Lee YH, Rho YH, Choi SJ et al (2005) Ankylosing spondylitis susceptibility loci defined by genome-search meta-analysis. J Hum Genet 50(9):453–459PubMedCrossRefGoogle Scholar
Carter KW, Pluzhnikov A, Timms AE et al (2007) Combined analysis of three whole genome linkage scans for Ankylosing Spondylitis. Rheumatology (Oxford) 46(5):763–771CrossRefGoogle Scholar
Breban M, Miceli-Richard C, Zinovieva E et al (2006) The genetics of spondyloarthropathies. Joint Bone Spine 73:355–362PubMedCrossRefGoogle Scholar
Freeston J, Barkham N, Hensor E et al (2007) Ankylosing spondylitis, HLA-B27 positivity and the need for biologic therapies. Joint Bone Spine 72(4):140–143CrossRefGoogle Scholar
Khan MA, Kushner I, Braun WE (1977) Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum 20(4):909–912PubMedCrossRefGoogle Scholar
Khan MA, Mathieu A, Sorrentino R et al (2007) The pathogenetic role of HLA-B27 and its subtypes. Autoimmun Rev 6(3):183–189PubMedCrossRefGoogle Scholar
Hamersma J, Cardon LR, Bradbury L et al (2001) Is disease severity in ankylosing spondylitis genetically determined? Arthritis Rheum 44(6):1396–1400PubMedCrossRefGoogle Scholar
Said-Nahal R, Miceli-Richard C, Berthelot JM et al (2000) The familial form of spondylarthropathy: a clinical study of 115 multiplex families. Groupe Francais d’Etude Genetique des Spondylarthropathies. Arthritis Rheum 43(6):1356–1365PubMedCrossRefGoogle Scholar
Porcher R, Said-Nahal R, D’Agostino MA et al (2005) Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families. Arthritis Rheum 53(2):263–271PubMedCrossRefGoogle Scholar
Said-Nahal R, Miceli-Richard C, D’Agostino MA et al (2001) Phenotypic diversity is not determined by independent genetic factors in familial spondylarthropathy. Arthritis Rheum 45(6):478–484PubMedCrossRefGoogle Scholar
Brown MA, Brophy S, Bradbury L et al (2003) Identification of major loci controlling clinical manifestations of ankylosing spondylitis. Arthritis Rheum 48(8):2234–2239PubMedCrossRefGoogle Scholar
Braun J, Brandt J, Listing J et al (2002) Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 359(9313):1187–1193PubMedCrossRefGoogle Scholar
Diedrichs-Mohring M, Wildner G (2005) Immunostimulatory and immunomodulatory peptides derived from the alpha1 domain of HLA-B27 in experimental autoimmune diseases in Lewis rats. Immunobiology 209(10):711–717PubMedCrossRefGoogle Scholar
Ramos M, Alvarez I, Sesma L et al (2002) Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins. J Biol Chem 277(40):37573–37581PubMedCrossRefGoogle Scholar
Frauendorf E, von Goessel H, May E et al (2003) 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 134(2):351–359PubMedCrossRefGoogle Scholar
Luthra-Guptasarma M, Singh B (2004) HLA-B27 lacking associated beta2-microglobulin rearranges to auto-display or cross-display residues 169–181: a novel molecular mechanism for spondyloarthropathies. FEBS Lett 575(1–3):1–8PubMedCrossRefGoogle Scholar
Tsai WC, Chen CJ, Yen JH et al (2002) Free HLA class I heavy chain-carrying monocytes–a potential role in the pathogenesis of spondyloarthropathies. J Rheumatol 29(5):966–972PubMedGoogle Scholar
Jaakkola E, Herzberg I, Laiho K et al (2006) Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis. Ann Rheum Dis 65(6):775–780PubMedCrossRefGoogle Scholar
Cauli A, Dessole G, Fiorillo MT et al (2002) Increased level of HLA-B27 expression in ankylosing spondylitis patients compared with healthy HLA-B27-positive subjects: a possible further susceptibility factor for the development of disease. Rheumatology (Oxford) 41(12):1375–1379CrossRefGoogle Scholar
Bird LA, Peh CA, Kollnberger S et al (2003) Lymphoblastoid cells express HLA-B27 homodimers both intracellularly and at the cell surface following endosomal recycling. Eur J Immunol 33(3):748–759PubMedCrossRefGoogle Scholar
Tran TM, Satumtira N, Dorris ML et al (2004) HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP. J Immunol 172(8):5110–5119PubMedGoogle Scholar