University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102, Australia.
NIHR Oxford Musculoskeletal Biomedical Research Unit and Comprehensive Biomedical Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK.
Nat Rev Rheumatol. 2016 Feb;12(2):81-91. doi: 10.1038/nrrheum.2015.133. Epub 2015 Oct 6.
Ankylosing spondylitis (AS), an immune-mediated arthritis, is the prototypic member of a group of conditions known as spondyloarthropathies that also includes reactive arthritis, psoriatic arthritis and enteropathic arthritis. Patients with these conditions share a clinical predisposition for spinal and pelvic joint dysfunction, as well as genetic associations, notably with HLA-B()27. Spondyloarthropathies are characterized by histopathological inflammation in entheses (regions of high mechanical stress where tendons and ligaments insert into bone) and in the subchondral bone marrow, and by abnormal osteoproliferation at involved sites. The association of AS with HLA-B()27, first described >40 years ago, led to hope that the cause of the disease would be rapidly established. However, even though many theories have been advanced to explain how HLA-B(*)27 is involved in AS, no consensus about the answers to this question has been reached, and no successful treatments have yet been developed that target HLA-B27 or its functional pathways. Over the past decade, rapid progress has been made in discovering further genetic associations with AS that have shed new light on the aetiopathogenesis of the disease. Some of these discoveries have driven translational ideas, such as the repurposing of therapeutics targeting the cytokines IL-12 and IL-23 and other factors downstream of this pathway. AS provides an excellent example of how hypothesis-free research can lead to major advances in understanding pathogenesis and to the development of innovative therapeutic strategies.
强直性脊柱炎（AS）是一种免疫介导的关节炎，是一组被称为脊柱关节炎的疾病的典型代表，这些疾病还包括反应性关节炎、银屑病关节炎和肠病性关节炎。这些疾病的患者都存在脊柱和骨盆关节功能障碍的临床倾向，以及遗传关联，特别是与 HLA-B()27 相关。脊柱关节炎的特征是在附着点（肌腱和韧带插入骨骼的高机械应力区域）和软骨下骨髓中出现组织病理学炎症，以及受累部位异常骨增生。AS 与 HLA-B()27 的关联早在 40 多年前就已被描述，这使得人们希望能迅速确定该病的病因。然而，尽管已经提出了许多理论来解释 HLA-B(*)27 如何参与 AS，但对于这个问题的答案仍未达成共识，也尚未开发出针对 HLA-B27 或其功能途径的成功治疗方法。在过去的十年中，在发现与 AS 相关的更多遗传关联方面取得了快速进展，这些关联为该疾病的发病机制提供了新的认识。其中一些发现推动了转化性的研究思路，例如针对细胞因子 IL-12 和 IL-23 及其下游途径的其他因素的治疗药物的重新定位。AS 为无假设研究如何导致对发病机制的重大认识进展以及创新性治疗策略的发展提供了一个极好的例子。
