Zhang Yiping, Shi Shuilang, Ciurli Christina, Poole A Robin
Joint Disease Laboratory and Departments of Surgery and Medicine, Shriners Hospital for Children, McGill University, Montreal H3G 1A6, Canada.
Curr Rheumatol Rep. 2002 Dec;4(6):507-12. doi: 10.1007/s11926-002-0058-1.
The pathology of ankylosing spondylitis (AS) and related spondyloarthropathies (SpA) characteristically involve a sacroiliitis and inflammation of the intervertebral discs (IVD) in the lumbar spine, and an enthesitis at sites of ligamentous insertions into bone. The proteoglycans aggrecan and versican are large molecules that aggregate with hyaluronic via a globular 1 domain. These domains share significant homology at the level of B and T cell epitope recognition. Both proteoglycans are present in the intervertebral disc and hyaline cartilages of the sacroiliac joint, as well as in entheses. Whereas aggrecan is most concentrated in the nucleus of the IVD and in articular cartilages and endplates, versican is generally absent from these tissues except in the sacroiliac joint, but is concentrated in ligaments and the annulus. Immunity to these molecules in BALB/c mice results in an AS-like pathology, including sacroiliitis, enthesitis, and discitis. The pathology of AS is closely associated with the expression of the class I molecule human leukocyte antigen-B27. Rats bearing this transgene develop an AS-like pathology, as well as other various signs of autoimmunity. Ankylosing spondylitis is characterized by an ankylosing pathology whereby bone formation in the annulus leads to intervertebral fusion. Mice bearing the ank/ank defect gene develop a bony ankylosis of the spine like that seen in advanced AS and related SpA. These three animal models provide insight into the pathogenesis of SpA, and opportunities to investigate their pathology in relationship to human disease where investigation of the pathobiology is very difficult, because of restricted access to involved tissues.
强直性脊柱炎（AS）及相关脊柱关节病（SpA）的病理特征通常包括骶髂关节炎、腰椎椎间盘（IVD）炎症以及韧带骨附着点处的附着点炎。蛋白聚糖聚集蛋白聚糖和多功能蛋白聚糖是通过球状1结构域与透明质酸聚集的大分子。这些结构域在B细胞和T细胞表位识别水平上具有显著的同源性。这两种蛋白聚糖都存在于椎间盘、骶髂关节的透明软骨以及附着点中。聚集蛋白聚糖最集中于IVD的髓核、关节软骨和终板，而多功能蛋白聚糖除了在骶髂关节外，通常不存在于这些组织中，但集中于韧带和纤维环。BALB/c小鼠对这些分子产生免疫会导致类似AS的病理改变，包括骶髂关节炎、附着点炎和椎间盘炎。AS的病理与I类分子人类白细胞抗原-B27的表达密切相关。携带该转基因的大鼠会出现类似AS的病理改变以及其他各种自身免疫迹象。强直性脊柱炎的特征是一种关节强硬性病理改变，即纤维环中的骨形成导致椎间融合。携带ank/ank缺陷基因的小鼠会出现脊柱骨性强直，类似于晚期AS和相关SpA中所见的情况。这三种动物模型为深入了解SpA的发病机制提供了线索，也为在难以对相关组织进行病理生物学研究的情况下，研究其病理与人类疾病的关系提供了机会。
