Free HLA class I heavy chain-carrying monocytes - A potential role in the pathogenesis of spondyloarthropathies

Objective. A fully complexed HLA-B27 molecule consists of a heavy chain, a peptide, and β₂-microglobulin (β₂m). The heavy chain can also exist free of β₂m. It has been proposed from animal and in vitro experiments that the free heavy chain is responsible for disease. We wanted to determine the following for patients with ankylosing spondylitis (AS): (1) are there cells expressing cell surface free heavy chains; (2) if so, which subset of cells has such capacity; (3) does expression vary with disease activity; (4) can we find free heavy chain-expressing cells at the site of inflammation that is characteristic of the disease; and (5) can such expression be induced in healthy subjects. Methods. Quantitative flow cytometry was carried out using antibodies directed separately against HLA class I complex, free heavy chain A or B alleles. Antibodies directed against other cell surface markers were used to identify cell types. Immunohistochemical staining was used to stain synovial tissue. Results. There was a high level of surface expression of free heavy chains in monocytes of patients with AS. The level exceeded those of normal controls and patients with rheumatoid arthritis. The level of expression correlated with the inflammation marker, erythrocyte sedimentation rate. The level of expression was enhanced when monocytes from healthy controls were driven to differentiation by longterm culture. Free heavy chain-expressing monocytes infiltrated the synovium of an involved hip joint of a patient with AS. Conclusion. This is the first patient-related evidence that surface free heavy chains of HLA-B27 have to be considered as potential disease-causing molecules.