Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Autoimmun Rev. 2022 Jul;21(7):103114. doi: 10.1016/j.autrev.2022.103114. Epub 2022 May 17.
From the introduction of hyperferritinemic syndrome concept, a growing body of evidence has suggested the role of ferritin as a pathogenic mediator and a relevant clinical feature in the management of patients with inflammatory diseases. From a pathogenic point of view, ferritin may directly stimulate the aberrant immune response by triggering the production of pro-inflammatory mediators in inducing a vicious pathogenic loop and contributing to the occurrence of cytokine storm syndrome. The latter has been recently defined as a clinical picture characterised by elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond that which could be attributed to a normal response to a pathogen It is noteworthy that the occurrence of hyperferritinemia may be correlated with the development of the cytokine storm syndrome in the context of an inflammatory disease. In addition to adult onset Still's disease, macrophage activation syndrome, catastrophic anti-phospholipids syndrome, and septic shock, recent evidence has suggested this association between ferritin and life-threatening evolution in patients with systemic lupus erythematosus, with anti-MDA5 antibodies in the context of poly-dermatomyositis, with severe COVID-19, and with multisystem inflammatory syndrome. The possible underlying common inflammatory mechanisms, associated with hyperferritinemia, may led to the similar clinical picture observed in these patients. Furthermore, similar therapeutic strategies could be suggested inhibiting pro-inflammatory cytokines and improving long-term outcomes in these disorders. Thus, it could be possible to expand the spectrum of the hyperferritinemic syndrome to those diseases burdened by a dreadful clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome. In addition, the assessment of ferritin may provide useful information to the physicians in clinical practice to manage these patients. Therefore, ferritin may be considered a relevant clinical feature to be used as biomarker in dissecting the unmet needs in the management of these disorders. Novel evidence may thus support an expansion of the spectrum of the hyperferritinemic syndrome to these diseases burdened by a life-threatening clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome.
从高血铁蛋白血症综合征概念的引入，越来越多的证据表明铁蛋白作为一种致病介质的作用，以及在炎症性疾病患者管理中的相关临床特征。从致病的角度来看，铁蛋白可能通过触发促炎介质的产生，直接刺激异常的免疫反应，导致致病的恶性循环，并导致细胞因子风暴综合征的发生。后者最近被定义为一种临床特征，表现为循环细胞因子水平升高、急性全身炎症症状和继发于器官功能障碍，超过了对病原体正常反应的程度。值得注意的是，在炎症性疾病的背景下，高血铁蛋白血症的发生可能与细胞因子风暴综合征的发展相关。除了成人斯蒂尔病、巨噬细胞活化综合征、灾难性抗磷脂综合征和感染性休克外，最近的证据表明，铁蛋白与系统性红斑狼疮患者的致命性疾病进展之间存在这种关联，抗 MDA5 抗体在多发性皮肌炎中，在严重的 COVID-19 中，以及在多系统炎症综合征中。可能与高血铁蛋白血症相关的潜在共同炎症机制可能导致这些患者观察到类似的临床特征。此外，抑制促炎细胞因子和改善这些疾病的长期预后的类似治疗策略也可以被建议。因此，高血铁蛋白血症综合征的范围可能扩大到那些与高血铁蛋白血症和细胞因子风暴综合征发生相关的可怕临床特征相关的疾病。此外，铁蛋白的评估可以为临床医生在临床实践中管理这些患者提供有用的信息。因此，铁蛋白可以被认为是一种相关的临床特征，可以作为生物标志物用于剖析这些疾病管理中的未满足需求。新的证据可能支持将高血铁蛋白血症综合征的范围扩大到那些与高血铁蛋白血症和细胞因子风暴综合征发生相关的危及生命的临床特征相关的疾病。
