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Rheumatology Advance Access published online on August 27, 2006
Rheumatology, doi:10.1093/rheumatology/kel305
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 15, 2006
Accepted July 21, 2006

Original Papers

Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles

Tim Raine 1, Damien Brown 1, Paul Bowness 2, J.S. Hill Gaston 3, Ashley Moffett 1, John Trowsdale 1, and Rachel L. Allen 1 *

1 Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK
2 Human Immunology Unit, Institute of Molecular Medicine, Oxford OX3 9DS, UK
3 Department of Medicine, Addenbrookes Hospital, Cambridge CB2 2QQ, UK

* To whom correspondence should be addressed.
Rachel L. Allen, E-mail: rla25{at}cam.ac.uk


  Abstract

Objectives. Major histocompatibility complex class I (MHC-I) proteins exist at the cell surface in antigen presenting forms and as {beta} 2m-independent free heavy chains (FHCs). FHCs have been implicated in spondyloarthritis, but little is known about their expression in healthy individuals. We studied FHC expression on various human cell types, comparing spondyloarthropathy patients with healthy and rheumatoid arthritis (RA) patient controls.

Methods. MHC-I expression was analysed by flow cytometry. FHC levels were normalized for overall MHC-I to generate a relative expression level. Relative FHC levels were analysed for peripheral blood and trophoblast samples from healthy volunteers, RA and spondyloarthropathy patients. Macrophages and dendritic cells were cultured in vitro to analyse changes following activation. Peripheral blood leucocytes from patients with ankylosing spondylitis (AS) and RA were treated with inflammatory stimuli and subsequent alterations in their relative FHC levels were analysed.

Results. We found consistent patterns of differential relative FHC expression across lymphocyte subpopulations and particularly high expression on extravillous trophoblast. FHCs were present at higher levels in a reactive arthritis (ReA) population than in healthy controls and RA patients; differences not merely due to the presence of Human Leucocyte Antigen (HLA) B27. Treatment of leucocytes from arthritic patients with bacterial lipopolysaccharide resulted in significant up-regulation of FHC compared with an HLA B27+ control population.

Conclusions. Our findings define normal levels and tissue expression of FHCs, and support the hypothesis that disregulation of heavy chain expression may play a pathogenic role in spondyloarthropathy.

Keywords: Free heavy chain; Ankylosing spondylitis; MHC; FHC; HLA B27; HLA G.
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