Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue

Oliwia Rysnik, Kirsty McHugh, Leonie van Duivenvoorde, Melissa van Tok, Giuliana Guggino, Joel Taurog, Simon Kollnberger, Francesco Ciccia, Dominique Baeten, Paul Bowness

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 (TG1) rats with M.tuberculosis-induced SpA. Methods: 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. 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 TG1 rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG1 rats prior to clinical arthritis. The expression of NC-B27 on B27 TG1 rat CD11b/c+, CD8α+, 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 TG1 rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA.

Original languageEnglish (US)
JournalJournal of Autoimmunity
DOIs
StateAccepted/In press - Feb 11 2016

Fingerprint

Spondylarthropathies
HLA Antigens
Joints
Lymphoid Tissue
Arthritis
Transgenic Rats
Animal Diseases
Ankle Joint
Ankylosing Spondylitis
Confocal Microscopy
Disease Progression
Tail
Flow Cytometry
Tuberculosis
Spleen
Immunohistochemistry
Ligands
Antibodies

Keywords

  • HLA class I free-heavy chains
  • HLA-B27
  • HLA-B27 transgenic rat model
  • Spondyloarthropathies

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Rysnik, O., McHugh, K., van Duivenvoorde, L., van Tok, M., Guggino, G., Taurog, J., ... Bowness, P. (Accepted/In press). Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue. Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2016.03.009

Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue. / Rysnik, Oliwia; McHugh, Kirsty; van Duivenvoorde, Leonie; van Tok, Melissa; Guggino, Giuliana; Taurog, Joel; Kollnberger, Simon; Ciccia, Francesco; Baeten, Dominique; Bowness, Paul.

In: Journal of Autoimmunity, 11.02.2016.

Research output: Contribution to journalArticle

Rysnik, O, McHugh, K, van Duivenvoorde, L, van Tok, M, Guggino, G, Taurog, J, Kollnberger, S, Ciccia, F, Baeten, D & Bowness, P 2016, 'Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue', Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2016.03.009
Rysnik, Oliwia ; McHugh, Kirsty ; van Duivenvoorde, Leonie ; van Tok, Melissa ; Guggino, Giuliana ; Taurog, Joel ; Kollnberger, Simon ; Ciccia, Francesco ; Baeten, Dominique ; Bowness, Paul. / Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue. In: Journal of Autoimmunity. 2016.
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abstract = "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 (TG1) rats with M.tuberculosis-induced SpA. Methods: 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. 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 TG1 rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG1 rats prior to clinical arthritis. The expression of NC-B27 on B27 TG1 rat CD11b/c+, CD8α+, 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 TG1 rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA.",
keywords = "HLA class I free-heavy chains, HLA-B27, HLA-B27 transgenic rat model, Spondyloarthropathies",
author = "Oliwia Rysnik and Kirsty McHugh and {van Duivenvoorde}, Leonie and {van Tok}, Melissa and Giuliana Guggino and Joel Taurog and Simon Kollnberger and Francesco Ciccia and Dominique Baeten and Paul Bowness",
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AU - Rysnik, Oliwia

AU - McHugh, Kirsty

AU - van Duivenvoorde, Leonie

AU - van Tok, Melissa

AU - Guggino, Giuliana

AU - Taurog, Joel

AU - Kollnberger, Simon

AU - Ciccia, Francesco

AU - Baeten, Dominique

AU - Bowness, Paul

PY - 2016/2/11

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N2 - 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 (TG1) rats with M.tuberculosis-induced SpA. Methods: 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. 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 TG1 rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG1 rats prior to clinical arthritis. The expression of NC-B27 on B27 TG1 rat CD11b/c+, CD8α+, 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 TG1 rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA.

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 (TG1) rats with M.tuberculosis-induced SpA. Methods: 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. 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 TG1 rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG1 rats prior to clinical arthritis. The expression of NC-B27 on B27 TG1 rat CD11b/c+, CD8α+, 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 TG1 rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA.

KW - HLA class I free-heavy chains

KW - HLA-B27

KW - HLA-B27 transgenic rat model

KW - Spondyloarthropathies

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