Systemic lupus erythematosus
Systemic lupus erythematosus
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系统性红斑狼疮
DOI：
10.1038/nrdp.2016.39
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发表时间：
2016-06-16
影响因子：
81.5
通讯作者：
Hughes, Graham
中科院分区：
文献类型：
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作者：
Kaul, Arvind;Gordon, Caroline;Hughes, Graham
系统性红斑狼疮（SLE）是一种自身免疫性疾病，可以影响许多器官，包括皮肤，关节，中枢神经系统和肾脏。育龄妇女和某些种族群体通常易患这种疾病。罕见的遗传性单基因补体缺陷与SLE密切相关，但大多数患者以多基因方式遗传该疾病。与环境因素的遗传相互作用，特别是紫外线照射，EB病毒感染和激素因素，可能引发疾病，导致细胞因子，T细胞，B细胞和巨噬细胞水平的免疫失调。由于SLE的异质性，诊断主要是临床的，仍然具有挑战性。分类标准有助于临床试验，但尽管如此，在过去的60年里，只有一种药物（即贝利木单抗）被批准用于SLE。10年死亡率有所改善，较旧药物（如环磷酰胺和糖皮质激素）的毒性副作用已被较新药物（如吗替麦考酚酯和糖皮质激素保留方案）部分抵消。然而，进一步的改善受到肾脏和神经精神疾病的不良影响以及诊断延迟的阻碍。SLE患者早发心血管疾病的风险增加以及免疫抑制治疗加重感染的风险增加，加重了这一负担。挑战仍然存在于治疗抵抗性疾病和疲劳等症状。更新的疗法可能会带来更好的结果，而干细胞和遗传技术的改进可能会在未来提供治疗方法。
Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.