Pediatric Translational Research Branch, NIAMS Intramural Research Program, NIH, USA.
Best Pract Res Clin Rheumatol. 2017 Dec;31(6):797-815. doi: 10.1016/j.berh.2018.07.012. Epub 2018 Aug 23.
The mechanism by which HLA-B27 predisposes to spondyloarthritis remains unresolved. Arthritogenic peptides have not been defined in humans and are not involved in experimental models of spondyloarthritis. Aberrant properties of HLA-B27 can activate the IL-23/IL-17 axis in HLA-B27 transgenic rats and humans. In HLA-B27-independent rodent models, spondyloarthritis can be driven by IL-23 triggering entheseal-resident CD4/CD8 T cells or CD4 Th17 T cells. These findings point toward noncanonical mechanisms linking HLA-B27 to the disease and provide a potential explanation for HLA-B27-negative spondyloarthritis. Gut microbial dysbiosis may be important in the development of spondyloarthritis. HLA-B27-induced changes in gut microbiota are complex and suggest an ecological model of dysbiosis in rodents. The importance of the IL-23/IL-17 axis in ankylosing spondylitis has been demonstrated by studies showing efficacy of IL-17. Although deciphering the precise role(s) of HLA-B27 in disease requires further investigation, considerable progress has been made in understanding this complex relationship.
HLA-B27 导致脊柱关节炎的机制仍未解决。人类尚未确定致病肽，且这些肽也不参与脊柱关节炎的实验模型。HLA-B27 的异常特性可在 HLA-B27 转基因大鼠和人类中激活 IL-23/IL-17 轴。在 HLA-B27 不依赖的啮齿动物模型中，IL-23 触发肌腱附着处固有 CD4/CD8 T 细胞或 CD4 Th17 T 细胞也可引发脊柱关节炎。这些发现指向将 HLA-B27 与疾病联系起来的非典型机制，并为 HLA-B27 阴性脊柱关节炎提供了潜在的解释。肠道微生物失调可能在脊柱关节炎的发病机制中起重要作用。HLA-B27 诱导的肠道微生物群变化复杂，并提示在啮齿动物中存在生态失调模型。IL-17 在强直性脊柱炎中的作用已通过证明 IL-17 疗效的研究得到证实。尽管阐明 HLA-B27 在疾病中的确切作用需要进一步研究，但在理解这种复杂关系方面已经取得了相当大的进展。
