Comparison of Th1/Th2 cytokine profiles between primary and secondary haemophagocytic lymphohistiocytosis.
Comparison of Th1/Th2 cytokine profiles between primary and secondary haemophagocytic lymphohistiocytosis.
复制标题
原发性和继发性噬血细胞性淋巴组织细胞增多症Th1/Th2细胞因子谱的比较
DOI：
10.1186/s13052-016-0262-7
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发表时间：
2016-05-21
影响因子：
3.6
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Chen Y;Wang Z;Luo Z;Zhao N;Yang S;Tang Y
背景噬血细胞性淋巴组织细胞增生症（Haemophagocyte lymphohistiocytosis，HLH）是一种严重威胁生命的免疫调节障碍性疾病，其中PRF 1、UNC 13 D、STX 11、STXBP 2、SH 2D 1A、XIAP和ITK等基因突变的HLH患者被报道为原发性HLH。由于不同的治疗选择，原发性和继发性HLH之间的区别至关重要。我们以前的研究表明，Th 1/Th 2细胞因子谱是HLH的诊断，但原发性和继发性HLH之间的细胞因子谱尚未进行比较。本研究的目的是测试是否Th 1/Th 2细胞因子谱可以作为一种工具，以区分原发性和继发性HLH.MethodsA共45例住院的中国儿童HLH在2010年2月至2012年9月期间，参加了这项研究。50名健康儿童作为对照组。使用基因组DNA样品对初级HLH相关基因进行测序。结果原发性HLH组（n= 4）包括1例PRF 1基因双等位基因杂合突变和3例SH 2D 1A基因半合子突变，其中1例为HLH患者，另1例为HLH患者，采用流式细胞术检测IFN-γ、TNF-α、IL-10、IL-6、IL-4和IL-2等Th 1/Th 2细胞因子水平。根据现有的遗传学数据，其他41例患者被归类为继发性HLH组。两组细胞因子水平比较，原发性HLH组IL-4水平显著低于继发性HLH组（P= 0.025），IFN-γ水平有显著低于继发性HLH组的趋势（P= 0.051）。IL-4和IFN-γ、IL-10、TNF-α、IL-2和IL-6水平的受试者工作特征（ROC）曲线下面积分别为0.841、0.799、0.506、0.494、0.457和0.250。ROC曲线显示IL-4浓度为1.7pg/ml时，鉴别原发性和继发性HLH的敏感性为70.7%，特异性为100.0%，IFN-γ浓度为433.9pg/ml时，鉴别原发性和继发性HLH的敏感性为51.2%，特异性为100.0%。细胞因子谱可作为快速鉴别原发性和继发性HLH的额外工具。
BackgroundHaemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation, and HLH patients with mutations in genes includingPRF1, UNC13D, STX11,STXBP2,SH2D1A, XIAP,andITKwere reported to be primary HLH. Due to the different treatment options, the differentiation between primary and secondary HLH is critical. Our previous studies have showed that a Th1/Th2 cytokine profile is diagnostic for HLH, yet the cytokine profiles between primary and secondary HLH have not been compared. The aim of the study was to test whether the Th1/Th2 cytokine profile could be used as a tool to differentiate between primary and secondary HLH.MethodsA total of 45 hospitalized Chinese children with HLH during the period of February 2010 through September 2012 were enrolled in the study. Fifty healthy children were enrolled as controls. Primary HLH related genes were sequenced using genomic DNA samples. The Th1/Th2 cytokine levels including interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10, IL-6, IL-4 and IL-2 were quantitatively determined by cytometric bead assay techniques.ResultsPrimary HLH group (n= 4) included one patient with biallelic heterozygous mutations inPRF1gene, and three patients with hemizygous mutation inSH2D1Agene. Based on the available genetic data, the other 41 patients were classified into the secondary HLH group. When compared the cytokine levels between the two groups, IL-4 level in primary-HLH was significantly lower than that in secondary HLH (P= 0.025), while IFN-γ level in primary HLH had a tendency of statistically lower than that in secondary HLH (P= 0.051). Area under receiver operating characteristic (ROC) curves of IL-4 and IFN-γ, IL-10, TNF-α, IL-2, and IL-6 levels were 0.841, 0.799, 0.506, 0.494, 0.457, and 0.250, respectively. ROC curves showed that 1.7 pg/ml of IL-4 had sensitivity and specificity for differentiation between primary and secondary HLH as 70.7 and 100.0 %, while 433.9 pg/ml of IFN-γ had sensitivity and specificity as 51.2 and 100.0 %, respectively.ConclusionsHLH patients with lower IL-4 and IFN-γ levels have higher possibility to be primary HLH. The cytokine profile may be used as an additional tool for the quick differential diagnosis between primary and secondary HLH.