Smith Judith A
Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, H4/472 CSC, Madison, WI, 53709-4108, USA,
Curr Allergy Asthma Rep. 2015 Jan;15(1):489. doi: 10.1007/s11882-014-0489-6.
Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. The long delay in diagnosis and insufficient response to currently available therapeutics both advocate for a greater understanding of disease pathogenesis. Genome-wide association studies of this highly genetic disease have implicated specific immune pathways, including the interleukin (IL)-17/IL-23 pathway, control of nuclear factor kappa B (NF-κB) activation, amino acid trimming for major histocompatibility complex (MHC) antigen presentation, and other genes controlling CD8 and CD4 T cell subsets. The relevance of these pathways has borne out in animal and human subject studies, in particular, the response to novel therapeutic agents. Genetics and the findings of autoantibodies in ankylosing spondylitis revisit the question of autoimmune vs. autoinflammatory etiology. As environmental partners to genetics, recent attention has focused on the roles of microbiota and biomechanical stress in initiating and perpetuating inflammation. Herein, we review these current developments in the investigation of ankylosing spondylitis pathogenesis.
强直性脊柱炎是一种隐匿性进展且使人衰弱的关节炎，累及中轴骨骼。诊断的长期延迟以及对现有治疗方法的反应不足都表明需要更深入地了解疾病的发病机制。对这种高度遗传性疾病进行的全基因组关联研究已表明特定的免疫途径，包括白细胞介素（IL）-17/IL-23途径、核因子κB（NF-κB）激活的控制、主要组织相容性复合体（MHC）抗原呈递的氨基酸修剪以及其他控制CD8和CD4 T细胞亚群的基因。这些途径的相关性已在动物和人体研究中得到证实，特别是对新型治疗药物的反应。强直性脊柱炎的遗传学和自身抗体的发现重新引发了关于自身免疫与自身炎症病因的问题。作为遗传学的环境因素，最近的研究重点集中在微生物群和生物力学应激在引发和维持炎症中的作用。在此，我们综述强直性脊柱炎发病机制研究中的这些最新进展。
