Rheumatology, Clinical Immunology and Allergy, University of Crete School of Medicine, 1 Voutes Street, Heraklion, Greece.
Ann Rheum Dis. 2010 Sep;69(9):1603-11. doi: 10.1136/ard.2010.135186.
Immune responses against endogenous nuclear antigens are characteristic of systemic lupus erythematosus (SLE), a highly pleiomorphic disease predominantly affecting young women of reproductive age. Genome-wide association studies have confirmed the importance of genes associated with the immune response as well as genes involved in endothelial function and tissue response to injury. Immune complexes, autoantibodies, complement, cytokines, endothelial injury and a thrombophilic state associated with antiphospholipid antibodies are important for mediating tissue dysfunction. If not treated promptly, a significant proportion of patients-especially those with more aggressive disease-accumulate irreversible damage. During the past decade, novel combinations of immunosuppressive drugs and biologicals have been added to the therapeutic armamentarium. At the same time, the emphasis in the management of lupus has shifted from individual drugs to a strategy that aims at early, sustained remission tailored to disease manifestations and severity with the lowest possible toxicity. Infections and accelerated atherosclerosis (attributed to both traditional and non-traditional risk factors) and thrombosis-related clinical events (including arterial, venous and pregnancy loss) represent a major challenge in the management of the disease. To avoid fragmentation and optimise medical care, evidence and expert-based recommendations have been developed. For the future the authors predict a new taxonomy on the basis of mechanisms rather than clinical empiricism, leading to targeted therapy.
自身免疫反应针对的是核内自身抗原，这是红斑狼疮（SLE）的一个特征，SLE 是一种高度多形性疾病，主要影响育龄期年轻女性。全基因组关联研究已经证实，与免疫反应相关的基因以及与内皮功能和组织对损伤反应相关的基因都很重要。免疫复合物、自身抗体、补体、细胞因子、内皮损伤以及与抗磷脂抗体相关的血栓形成倾向对于介导组织功能障碍都很重要。如果不及时治疗，相当一部分患者（尤其是病情更严重的患者）会积累不可逆转的损伤。在过去十年中，新型免疫抑制剂和生物制剂的组合已被添加到治疗方案中。与此同时，狼疮的治疗重点已经从单一药物转变为一种策略，即针对疾病表现和严重程度，尽早、持续缓解疾病，同时将毒性降至最低。感染和动脉粥样硬化加速（归因于传统和非传统危险因素）以及与血栓形成相关的临床事件（包括动脉、静脉和妊娠丢失）是该疾病管理中的一个主要挑战。为了避免碎片化并优化医疗护理，已经制定了基于证据和专家建议的建议。未来，作者预测将基于机制而非临床经验主义建立新的分类法，从而实现靶向治疗。
