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

• Main Authors: WEN CHAN TSAI, 蔡文展
• Other Authors: Hong-Wen Liu
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/86542956598584364035

博士 === 高雄醫學大學 === 醫學研究所 === 90 === Abstract Objective. A fully complexed HLA-B27 molecule consists of a heavy chain, a peptide and the 2-microglobulin (2m). The heavy chain can also exist free of 2m. It has been proposed from animal experiments and from in vitro experiments that it is the free heavy chain that is responsible for disease. The objectives of this study are to find out in Ankylosing spondylitis (AS) patients (1) if there are indeed cells expressing cell surface free heavy chains; (2) if so, which subset of cells have such capacity; (3) whether the expression varies with disease activities and; (4) can we find free heavy chain-expressing cells in the site of inflammation which is characteristic of the disease; (5) can such expression be induced in normal subjects. Methods. Quantitative flow cytometry were carried out using antibodies directed separately against HLA class I complexes, free heavy chain A or B alleles. Antibodies directed against other cell surface markers are used to identify cell types. Immunohistochemical staining was used to stain the sample from a synovial tissue. Results. (1) There is high level of surface expression of free heavy chains in monocytes of patients with AS. The level exceeds those of normal control and rheumatoid arthritis (RA). (2) The level of expression correlates with inflammation marker ESR. (3) The level of expression is enhanced when monocytes from normal controls are driven to differentiation by long-term culture. (4) Free heavy chain-expressing monocytes infiltrate in the synovium of hip joint which was involved in an AS patient. Conclusion. This provides the first time patient-related evidences that surface free heavy chains of HLA-B27 have to be considered as potential disease-causing molecules. In addition, we will discuss the potential role of unfolded protein response in the pathogenesis of spondyloarthropathy.