Manou-Stathopoulou Sotiria, Lewis Myles J
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Semin Immunol. 2021 Dec;58:101649. doi: 10.1016/j.smim.2022.101649. Epub 2022 Sep 3.
Systemic Autoimmune Rheumatic Diseases, including Rheumatoid Arthritis, Systemic Lupus Erythematosus and Sjogren's syndrome, are characterised by a loss of immune tolerance and chronic inflammation. There is marked heterogeneity in clinical and molecular phenotypes in each condition, and the aetiology of these is unclear. NF-κB is an inducible transcription factor that is critical in the physiological inflammatory response, and which has been implicated in chronic inflammation. Genome-wide association studies have linked risk alleles related to the NF-κB pathway to the pathogenesis of multiple Systemic Autoimmune Rheumatic Diseases. This review describes how cell- and pathway-specific NF-κB activation contribute to the spectrum of clinical phenotypes and molecular pathotypes in rheumatic disease. Potential clinical applications are explored, including therapeutic interventions and utilisation of NF-κB as a biomarker of disease subtypes and treatment response.
系统性自身免疫性风湿病，包括类风湿关节炎、系统性红斑狼疮和干燥综合征，其特征是免疫耐受丧失和慢性炎症。每种疾病在临床和分子表型上都存在显著的异质性，其病因尚不清楚。核因子κB（NF-κB）是一种诱导型转录因子，在生理性炎症反应中起关键作用，并且与慢性炎症有关。全基因组关联研究已将与NF-κB信号通路相关的风险等位基因与多种系统性自身免疫性风湿病的发病机制联系起来。本综述描述了细胞和信号通路特异性的NF-κB激活如何导致风湿性疾病临床表型和分子病理类型的多样性。探讨了潜在的临床应用，包括治疗干预以及将NF-κB用作疾病亚型和治疗反应的生物标志物。
