Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Clin Exp Immunol. 2021 Feb;203(2):174-182. doi: 10.1111/cei.13543. Epub 2020 Nov 23.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a challenge. Interleukin 18 (IL-18) is emerging as a potential biomarker for HLH/MAS but is currently not a part of diagnostic criteria. This systematic review aimed to assess the potential role of IL-18 in the diagnosis and monitoring of HLH and MAS, and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase were searched on 30 January 2020. Studies included all subtypes of HLH and a range of underlying disorders in both children and adults. A total of 14 studies were included. Generally, serum IL-18 was elevated in both primary and secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with healthy individuals; thus, serum IL-18 may be able to discriminate between HLH and other inflammatory conditions. Significantly increased IL-18 (> 10 000 pg/ml) was also consistently described in MAS compared with other subtypes of HLH. The ability of IL-18 to distinguish MAS from systemic juvenile idiopathic arthritis (JIA) is less unambiguous, as IL-18 levels > 100 000 pg/ml were described in sJIA patients both with and without MAS. IL-18 may help to differentiate between HLH subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, only few and relatively small studies exist on the subject. Larger, prospective multi-center studies are called for to assess the diagnostic precision of IL-18 for HLH and MAS.
噬血细胞性淋巴组织细胞增生症(HLH)是一种危及生命的、炎症过度活跃的疾病,其特征是多器官衰竭、发热和血细胞减少症。HLH 及其亚型巨噬细胞活化综合征(MAS)的诊断仍然具有挑战性。白细胞介素 18(IL-18)作为 HLH/MAS 的潜在生物标志物而备受关注,但目前尚未纳入诊断标准。本系统评价旨在评估 IL-18 在 HLH 和 MAS 的诊断和监测中的潜在作用,且按照系统评价和荟萃分析的首选报告项目(PRISMA)指南进行。2020 年 1 月 30 日在 PubMed 和 Embase 上进行了检索。研究纳入了所有 HLH 亚型和儿童及成人各种基础疾病。共纳入了 14 项研究。通常情况下,原发性和继发性 HLH(>1000pg/ml)的血清 IL-18 水平高于其他炎症状态和健康个体,因此血清 IL-18 可能能够区分 HLH 和其他炎症状态。MAS 与其他 HLH 亚型相比,IL-18 水平显著升高(>10000pg/ml)。IL-18 区分 MAS 与全身幼年特发性关节炎(JIA)的能力则不那么明确,因为在有或没有 MAS 的 sJIA 患者中,IL-18 水平均>100000pg/ml。IL-18 可能有助于区分 HLH 亚型和其他炎症状态。由于 HLH 和 MAS 是罕见疾病,因此目前关于该主题的研究较少且相对较小。需要开展更大规模的前瞻性多中心研究,以评估 IL-18 对 HLH 和 MAS 的诊断精度。