Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK.
Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, UK.
Clin Exp Immunol. 2018 Jul;193(1):3-12. doi: 10.1111/cei.13101. Epub 2018 Feb 2.
Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody-mediated autoimmune diseases cluster more closely with each other than autoantibody-negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.
免疫介导的炎症性疾病（IMIDs）的特征是正常免疫反应失调，导致炎症。由于它们通常是慢性疾病，并伴有相关的合并症，因此在人群中疾病负担很高。例如，红斑狼疮、类风湿性关节炎、克罗恩病和 1 型糖尿病。自全基因组关联研究出现以来，人们已经发现，导致广泛的 IMIDs 的易感基因座之间存在相当大的遗传重叠。了解 IMIDs 之间的遗传风险和遗传重叠程度，可能有助于确定哪些基因控制着不同疾病的哪些方面；它可能为许多这类疾病确定潜在的新治疗靶点，和/或有助于为最初开发用于不同疾病的现有治疗方法重新定位。研究结果表明，与抗自身抗体阴性疾病（如银屑病、银屑病关节炎、克罗恩病和强直性脊柱炎）相比，抗自身抗体介导的自身免疫性疾病彼此之间的聚类更为紧密；而后者形成了一个血清阴性的遗传聚类。遗传聚类在很大程度上反映了对现有生物治疗的已知反应，但也讨论了治疗反应的明显异常。
