title: Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue.
abstract: Human leukocyte antigen (HLA)-B27 (B27) is the strongest genetic factor associated with development of Ankylosing Spondylitis and other spondyloarthropathies (SpA), yet the role it plays in disease pathogenesis remains unclear. We investigated the expression of potentially pathogenic non-conventional heavy chain forms (NC) of B27 in synovial and intestinal tissues obtained from SpA patients. We also determined the presence of NC-B27 in joints, lymphoid and gastrointestinal tissue from B27 transgenic (TG(1)) rats with M.tuberculosis-induced SpA.
  
  
  
  Expression of NC-B27 in human SpA joints and gut and in (21-3 × 283-2)F1 HLA-B27/Huβ2m rat tissue was determined by immunohistochemistry, flow cytometry and confocal microscopy analysis using HC10 and HD6 antibodies.
  
  
  
  Both HC10- and HD6-reactive HLA molecules were present in synovial tissue from SpA patients. Both NC-B27 and KIR3DL2, a ligand for NC-B27, were expressed in inflamed terminal ileal tissues in patients with early SpA. Infiltrating cells in inflamed joint tissues isolated from B27 TG(1) rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG(1) rats prior to clinical arthritis. The expression of NC-B27 on B27 TG(1) rat CD11b/c(+), CD8α(+), cells from spleens and LNs increased with animal age and disease progression.
  
  
  
  Non-conventional HLA class 1 molecules are expressed on resident and infiltrating cells in both synovial and GI tissues in human SpA. NC-B27 expression in joints and lymphoid tissues from B27 TG(1) rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK. Electronic address: oliwia.rysnik@gtc.ox.ac.uk.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Rysnik
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: McHugh
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: van Duivenvoorde
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Melissa
authors.initials: M
authors.lastname: van Tok
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Department of Internal Medicine, Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Taurog
authors.affiliation: Cardiff Institute of Infection & Immunity, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Kollnberger
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bowness
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D016723:Bone Remodeling / Q000235:genetics / Q000276:immunology; D018845:CD11 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051381:Rats; D055647:Rats, Transgenic; D054347:Receptors, KIR3DL2 / Q000235:genetics / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C517765:DEFA6 protein, human; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D054347:Receptors, KIR3DL2; D023084:alpha-Defensins
keywords: HLA class I free-heavy chains; HLA-B27; HLA-B27 transgenic rat model; Spondyloarthropathies