Raine T, Brown D, Bowness P, Hill Gaston J S, Moffett A, Trowsdale J, Allen R L
Department of Pathology, Tennis Court Road, Cambridge, CB2 1QP, UK.
Rheumatology (Oxford). 2006 Nov;45(11):1338-44. doi: 10.1093/rheumatology/kel305. Epub 2006 Aug 27.
Major histocompatibility complex class I (MHC-I) proteins exist at the cell surface in antigen presenting forms and as beta2m-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.
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.
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.
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.
主要组织相容性复合体I类（MHC-I）蛋白以抗原呈递形式存在于细胞表面，并作为与β2微球蛋白无关的游离重链（FHC）存在。FHC与脊柱关节炎有关，但对其在健康个体中的表达了解甚少。我们研究了FHC在各种人类细胞类型上的表达，将脊柱关节病患者与健康对照者及类风湿关节炎（RA）患者进行比较。
通过流式细胞术分析MHC-I的表达。将FHC水平针对总的MHC-I进行标准化，以生成相对表达水平。分析健康志愿者、RA患者和脊柱关节病患者外周血及滋养层样本的相对FHC水平。体外培养巨噬细胞和树突状细胞，以分析激活后的变化。对强直性脊柱炎（AS）和RA患者的外周血白细胞进行炎症刺激处理，并分析其相对FHC水平的后续变化。
我们发现淋巴细胞亚群中存在一致的相对FHC差异表达模式，并且在绒毛外滋养层上表达特别高。反应性关节炎（ReA）人群中的FHC水平高于健康对照者和RA患者；差异不仅仅归因于人类白细胞抗原（HLA）B27的存在。与HLA B27+对照人群相比，用细菌脂多糖处理关节炎患者的白细胞导致FHC显著上调。
我们的研究结果确定了FHC的正常水平和组织表达，并支持重链表达失调可能在脊柱关节病中起致病作用这一假说。
