PMID- 27036372 OWN - NLM STAT- MEDLINE DCOM- 20170406 LR - 20210402 IS - 1095-9157 (Electronic) IS - 0896-8411 (Print) IS - 0896-8411 (Linking) VI - 70 DP - 2016 Jun TI - Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue. PG - 12-21 LID - S0896-8411(16)30022-1 [pii] LID - 10.1016/j.jaut.2016.03.009 [doi] AB - OBJECTIVES: 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. METHODS: Expression of NC-B27 in human SpA joints and gut and in (21-3 x 283-2)F1 HLA-B27/Hubeta2m rat tissue was determined by immunohistochemistry, flow cytometry and confocal microscopy analysis using HC10 and HD6 antibodies. RESULTS: 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(+), CD8alpha(+), cells from spleens and LNs increased with animal age and disease progression. CONCLUSIONS: 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. CI - Copyright (c) 2016 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Rysnik, Oliwia AU - Rysnik O AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK. Electronic address: oliwia.rysnik@gtc.ox.ac.uk. FAU - McHugh, Kirsty AU - McHugh K AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK. FAU - van Duivenvoorde, Leonie AU - van Duivenvoorde L AD - Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. FAU - van Tok, Melissa AU - van Tok M AD - Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. FAU - Guggino, Giuliana AU - Guggino G AD - Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Universita di Palermo, Italy. FAU - Taurog, Joel AU - Taurog J AD - Department of Internal Medicine, Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas, USA. FAU - Kollnberger, Simon AU - Kollnberger S AD - Cardiff Institute of Infection & Immunity, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK. FAU - Ciccia, Francesco AU - Ciccia F AD - Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Universita di Palermo, Italy. FAU - Baeten, Dominique AU - Baeten D AD - Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. FAU - Bowness, Paul AU - Bowness P AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK. LA - eng GR - 19611/ARC_/Arthritis Research UK/United Kingdom GR - 19611/VAC_/Versus Arthritis/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160329 PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 RN - 0 (CD11 Antigens) RN - 0 (CD8 Antigens) RN - 0 (CD8 antigen, alpha chain) RN - 0 (DEFA6 protein, human) RN - 0 (HLA-B27 Antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Receptors, KIR3DL2) RN - 0 (alpha-Defensins) SB - IM MH - Animals MH - Arthritis, Experimental MH - Bone Remodeling/genetics/immunology MH - CD11 Antigens/metabolism MH - CD8 Antigens/metabolism MH - Disease Models, Animal MH - Gastrointestinal Diseases/*genetics/immunology/metabolism/pathology MH - *Gene Expression MH - HLA-B27 Antigen/*genetics/immunology/metabolism MH - Histocompatibility Antigens Class I/genetics/immunology/metabolism MH - Humans MH - Rats MH - Rats, Transgenic MH - Receptors, KIR3DL2/genetics/metabolism MH - Spondylitis, Ankylosing/*genetics/immunology/metabolism/pathology MH - Synovial Membrane/metabolism/pathology MH - alpha-Defensins/genetics/metabolism PMC - PMC4871811 OTO - NOTNLM OT - HLA class I free-heavy chains OT - HLA-B27 OT - HLA-B27 transgenic rat model OT - Spondyloarthropathies EDAT- 2016/04/03 06:00 MHDA- 2017/04/07 06:00 PMCR- 2016/06/01 CRDT- 2016/04/03 06:00 PHST- 2016/02/11 00:00 [received] PHST- 2016/03/11 00:00 [revised] PHST- 2016/03/12 00:00 [accepted] PHST- 2016/04/03 06:00 [entrez] PHST- 2016/04/03 06:00 [pubmed] PHST- 2017/04/07 06:00 [medline] PHST- 2016/06/01 00:00 [pmc-release] AID - S0896-8411(16)30022-1 [pii] AID - 10.1016/j.jaut.2016.03.009 [doi] PST - ppublish SO - J Autoimmun. 2016 Jun;70:12-21. doi: 10.1016/j.jaut.2016.03.009. Epub 2016 Mar 29.