PDF(Pubmed)
Abstract：
High ferritin is an important and sensitive biomarker for hemophagocytic lymphohistiocytosis (HLH), a diverse and deadly group of cytokine storm syndromes. Early action to prevent immunopathology in HLH often includes empiric immunomodulation, which can complicate etiologic work-up and prevent collection of early/pre-treatment research samples. To address this, we instituted an alert system where serum ferritin > 1000ng/mL triggered real-time chart review, assessment of whether the value reflected \"inflammatory hyperferritnemia (IHF)\", and biobanking of remnant samples from consenting IHF patients. We extracted relevant clinical data; periodically measured serum total IL-18, IL-18 binding protein (IL-18BP), and CXCL9; retrospectively classified patients by etiology into infectious, rheumatic, or immune dysregulation; and subjected a subgroup of samples to a 96-analyte biomarker screen. 180 patients were identified, 30.5% of which had IHF. Maximum ferritin levels were significantly higher in patients with IHF than with either hemoglobinopathy or transplant, and highly elevated total IL-18 levels were distinctive to patients with Stills Disease and/or Macrophage Activation Syndrome (MAS). Multi-analyte analysis showed elevation in proteins associated with cytotoxic lymphocytes in all IHF samples when compared to healthy controls and depression of proteins such as ANGPT1 and VEGFR2 in samples from hyperferritinemic sepsis patients relative to non-sepsis controls. This single-center, real-time IFH screen proved feasible and efficient, validated prior observations about the specificity of IL-18, enabled early sample collection from a complex population, suggested a unique vascular biomarker signature in hyperferritinemic sepsis, and expanded our understanding of IHF heterogeneity.
摘要：
高铁蛋白是噬血细胞性淋巴组织细胞增生症(HLH)的重要而敏感的生物标志物,一组多样化的致命的细胞因子风暴综合征。预防HLH免疫病理学的早期作用通常包括经验性免疫调节，这会使病因学检查复杂化，并阻止收集早期/治疗前的研究样本。为了解决这个问题，我们建立了一个警报系统，血清铁蛋白>1000ng/mL触发实时图表审查，评估该值是否反映了“炎症性高血铁（IHF）”，并对同意的IHF患者的残余样本进行生物分析。提取相关临床资料;定期测定血清总IL-18、IL-18结合蛋白(IL-18BP),和CXCL9；回顾性地将患者按病因分为感染性，风湿病,或免疫失调;并对样品亚组进行96分析物生物标志物筛选。180名患者被确认，其中30.5%有IHF。IHF患者的最高铁蛋白水平明显高于血红蛋白病或移植患者，和高度升高的总IL-18水平对于患有Stills病和/或巨噬细胞活化综合征（MAS）的患者是独特的。多分析物分析显示，与健康对照相比，所有IHF样品中与细胞毒性淋巴细胞相关的蛋白质升高，并且相对于非败血症对照，高铁蛋白败血症患者样品中的ANGPT1和VEGFR2等蛋白质降低。这个单一中心，实时IFH屏幕被证明是可行和高效的，验证了先前关于IL-18特异性的观察结果，能够从复杂群体中早期收集样本，在高铁蛋白血症性败血症中提出了一种独特的血管生物标志物特征，扩大了我们对IHF异质性的理解。
