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

J Autoimmun. 2016 Jun;70:12-21. doi: 10.1016/j.jaut.2016.03.009. Epub 2016 Mar 29.

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 (TG(1)) 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 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.

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.

Keywords: HLA class I free-heavy chains; HLA-B27; HLA-B27 transgenic rat model; Spondyloarthropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental
  • Bone Remodeling / genetics
  • Bone Remodeling / immunology
  • CD11 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Disease Models, Animal
  • Gastrointestinal Diseases / genetics*
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / pathology
  • Gene Expression*
  • HLA-B27 Antigen / genetics*
  • HLA-B27 Antigen / immunology
  • HLA-B27 Antigen / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Rats
  • Rats, Transgenic
  • Receptors, KIR3DL2 / genetics
  • Receptors, KIR3DL2 / metabolism
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / metabolism
  • Spondylitis, Ankylosing / pathology
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • alpha-Defensins / genetics
  • alpha-Defensins / metabolism

Substances

  • CD11 Antigens
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • HLA-B27 Antigen
  • Histocompatibility Antigens Class I
  • Receptors, KIR3DL2
  • alpha-Defensins
  • alpha-defensin 6, human