Hyperferritinemia Screening to Aid Identification and Differentiation of Patients with Hyperinflammatory Disorders

IF 7.2 2区 医学 Q1 IMMUNOLOGY
Hallie A. Carol, Adam S. Mayer, Michael S. Zhang, Vinh Dang, Jemy Varghese, Zachary Martinez, Corinne Schneider, Joy (Elizabeth) Baker, Paul Tsoukas, Edward M. Behrens, Randy Q. Cron, Caroline Diorio, Lauren A. Henderson, Grant Schulert, Pui Lee, Kate F. Kernan, Scott W. Canna
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Abstract

High ferritin is an important and sensitive biomarker for the various forms of 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 at UPMC Children’s Hospital where serum ferritin > 1000 ng/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 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.

Abstract Image

筛查高铁蛋白血症,帮助识别和区分高炎症性疾病患者
高铁蛋白是各种形式的嗜血细胞淋巴组织细胞增多症(HLH)的重要而敏感的生物标志物,HLH 是一组多样而致命的细胞因子风暴综合征。预防 HLH 免疫病理的早期措施通常包括经验性免疫调节,这会使病因检查复杂化,并妨碍收集早期/治疗前的研究样本。为了解决这个问题,我们在UPMC儿童医院建立了一个警报系统,血清铁蛋白超过1000纳克/毫升就会触发实时病历审查,评估该值是否反映了 "炎症性高铁蛋白血症(IHF)",并从同意的IHF患者身上采集残余样本。我们提取了相关临床数据;定期测量血清总 IL-18、IL-18 结合蛋白(IL-18BP)和 CXCL9;根据病因将患者回顾性地分为感染性、风湿性或免疫失调性;并对样本子群进行 96 个分析物生物标记筛选。结果发现了 180 名患者,其中 30.5% 患有 IHF。IHF患者的最大铁蛋白水平明显高于血红蛋白病或移植患者,IL-18总水平的高度升高是Stills病和/或巨噬细胞活化综合征(MAS)患者的特征。多分析物分析表明,与健康对照组相比,所有 IHF 样本中与细胞毒性淋巴细胞相关的蛋白质都升高了,而与非败血症对照组相比,高铁蛋白血症患者样本中的 ANGPT1 和 VEGFR2 等蛋白质则降低了。这种实时 IFH 筛选证明是可行且高效的,验证了之前关于 IL-18 特异性的观察结果,实现了从复杂人群中早期采集样本,提出了高铁蛋白血症脓毒症患者独特的血管生物标志物特征,并拓展了我们对 IHF 异质性的认识。
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来源期刊
CiteScore
12.20
自引率
9.90%
发文量
218
审稿时长
2 months
期刊介绍: The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.
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