Rheumatology Advance Access originally published online on August 27, 2006
Rheumatology 2006 45(11):1338-1344; doi:10.1093/rheumatology/kel305
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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
Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, 1Human Immunology Unit, Institute of Molecular Medicine, Oxford OX3 9DS and 2Department of Medicine, Addenbrookes Hospital, Cambridge CB2 2QQ, UK.
Correspondence to: Rachel L. Allen, DPhil, Department of Pathology, Tennis Court Road, Cambridge, CB2 1QP, UK. E-mail: rla25{at}cam.ac.uk
Objectives. Major histocompatibility complex class I (MHC-I) proteins exist at the cell surface in antigen presenting forms and as ß2m-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.
KEY WORDS: Free heavy chain, Ankylosing spondylitis, MHC, FHC, HLA B27, HLA G