Section of Musculoskeletal Diseases, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Chapel Allerton Hospital, Chapeltown Road, Leeds, West Yorkshire LS7 4SA, UK.
Division of Rheumatology, University of Ottawa, Arthritis Center, 1967 Riverside Drive, Ottawa, ON K1H 7W9, Canada.
Nat Rev Rheumatol. 2015 Dec;11(12):731-40. doi: 10.1038/nrrheum.2015.147. Epub 2015 Nov 3.
The spondyloarthropathies comprise ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA) and arthritis associated with inflammatory bowel disease. In this Perspectives article, we describe how Behçet disease and several clinically distinct spondyloarthropathies-all associated with MHC class I (MHC-I) alleles such as HLA-B()51, HLA-C()0602 and HLA-B()27 and epistatic ERAP-1 interactions-have a shared immunopathogenetic basis. As a unifying concept, we propose that barrier dysfunction in environmentally exposed organs such as the skin, and aberrant innate immune reactions at sites of mechanical stress, can often trigger secondary adaptive immune CD8(+) T-cell responses with prominent neutrophilic inflammation that culminate in exacerbation and recurrence of these diseases. Of note, these 'MHC-I-opathies' show a differential immunopathology, probably reflecting antigenic differences within target tissues: HLA-B()51 is linked to ocular and mucocutaneous disease but not gut involvement, and HLA-C(*)0602 is linked to type I psoriasis but not scalp or nail disease.
脊柱关节病包括强直性脊柱炎（AS）、反应性关节炎、银屑病关节炎（PsA）和与炎症性肠病相关的关节炎。在这篇观点文章中，我们描述了如何将白塞病和几种临床上明显不同的脊柱关节病（均与 MHC I 类（MHC-I）等位基因如 HLA-B()51、HLA-C()0602 和 HLA-B()27 以及 ERAP-1 相互作用有关）具有共同的免疫发病基础。作为一个统一的概念，我们提出，环境暴露器官（如皮肤）的屏障功能障碍，以及机械应激部位异常的固有免疫反应，通常可以触发以中性粒细胞炎症为特征的继发性适应性免疫 CD8(+)T 细胞反应，最终导致这些疾病的加重和复发。值得注意的是，这些“MHC-I 相关疾病”表现出不同的免疫病理学，可能反映了靶组织内的抗原差异：HLA-B()51 与眼和黏膜疾病有关，但与肠道受累无关，而 HLA-C(*)0602 与 I 型银屑病有关，但与头皮或指甲疾病无关。
