Loh Jia Tong, Lam Kong-Peng
Singapore Immunology Network, Agency for Science, Technology and Research, S138648 Singapore, Republic of Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, S117545 Singapore, Republic of Singapore.
Rheumatol Immunol Res. 2022 Oct 20;3(3):120-127. doi: 10.2478/rir-2022-0020. eCollection 2022 Oct.
Rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), are a group of auto-inflammatory disorders associated with substantial morbidity and mortality. One unifying feature of these diseases is the presence of abnormal neutrophils exhibiting dysregulated neutrophil extracellular trap (NET) release, reactive oxygen species (ROS) production, degranulation, and pro-inflammatory cytokines secretion. Moreover, the release of autoantigens associated with NETs promotes the generation of autoantibodies and a breakdown of self-tolerance, thereby perpetuating inflammation and tissue injury in these patients. In recent years, targeted therapies directed at neutrophilic effector functions have shown promising results in the management of rheumatic diseases. In this review, we will highlight the emerging roles of neutrophils in the onset and progression of rheumatic diseases, and further discuss current and future therapeutic approaches targeting the pathogenic functions of neutrophils, which can modulate inflammation and hence improve patients' survival and quality of life.
风湿性疾病,包括类风湿关节炎(RA)、系统性红斑狼疮(SLE)和抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV),是一组与高发病率和死亡率相关的自身炎症性疾病。这些疾病的一个共同特征是存在异常中性粒细胞,表现为中性粒细胞胞外诱捕网(NET)释放失调、活性氧(ROS)产生、脱颗粒以及促炎细胞因子分泌。此外,与NETs相关的自身抗原释放促进自身抗体的产生和自身耐受性的破坏,从而使这些患者的炎症和组织损伤持续存在。近年来,针对中性粒细胞效应功能的靶向治疗在风湿性疾病的管理中显示出了有前景的结果。在这篇综述中,我们将强调中性粒细胞在风湿性疾病发病和进展中的新作用,并进一步讨论针对中性粒细胞致病功能的当前和未来治疗方法,这些方法可以调节炎症,从而提高患者的生存率和生活质量。