The Correlation of Iron Metabolism Indexes,Cytokines,and Liver Function in Patients with Hemophagocytic Syndrome
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摘要:
目的 通过分析铁代谢指标、肝功能及细胞因子水平初步探讨噬血细胞综合征患者铁蛋白升高的原因。 方法 收集云南省第一人民医院2021年9月至2024年5月收治的噬血细胞综合征患者及对照组(铁蛋白升高的非噬血细胞综合征患者)各41例,进行铁代谢、细胞因子、肝功能检测,分析这些指标在2组间的差异及与铁蛋白的关系。 结果 噬血细胞综合征患者铁蛋白明显高于对照组(P < 0.01),可溶性转铁蛋白受体明显低于对照组(P < 0.01),细胞因子IL-4、IL-8、IL-10、IL-1β、IL-2、IFN-γ、TNF-α、TNF-β、IL-17A、IL-17F明显高于对照组(P < 0.05),转氨酶、胆红素及乳酸脱氢酶明显高于对照组(P < 0.01),铁蛋白与铁代谢指标无明显相关性,与细胞因子IL-4负相关,IL-8、IL-10正相关,与LDH、ALT、AST正相关(P < 0.05)。 结论 噬血细胞综合征患者铁蛋白明显升高,但铁代谢指标与对照组无明显差异,噬血细胞综合征发病时多有明显炎症反应及肝损害,铁蛋白的升高与铁代谢指标无相关性,与炎症及肝损伤相关。 Abstract:Objective To investigate preliminarily the causes of elevated ferritin in patients with hemophagocytic syndrome by analyzing the iron metabolism indexes, liver function and cytokine levels. Methods 41 patients with the hemophagocytic syndrome and another 41 non-hemophagocytic syndrome patients with the elevated ferritin levels (as the control group) admitted to the First People’ s Hospital of Yunnan Province from September 2021 to May 2024 were recruited for iron metabolism, cytokine and liver function tests, and the differences between these indexes and their relationship with the ferritin were analyzed. Results Patients with the hemophagocytic syndrome had the significantly higher levels of ferritin and lower levels of soluble transferrin receptor compared to the control group. Cytokines IL-4, IL-8, IL-10, IL-1 β, IL-2, IFN - γ, TNF - α, TNF - β, IL-17A, and IL-17F were significantly higher than those in the control group, while transaminase, bilirubin, and lactate dehydrogenase were significantly higher than those in the control group. There was no significant correlation between ferritin and iron metabolism indicators, but it was negatively correlated with cytokine IL-4, positively correlated with IL-8 and IL-10, and positively correlated with LDH, ALT, and AST. Conclusion The ferritin of patients with hemophagocytic syndrome is significantly increased, but the iron metabolism process is not significantly different from that of the control group, and there are obvious inflammatory reactions and liver damage at the onset of the disease.The increase of ferritin is not correlated with iron metabolism indexes, but is related to the inflammation and liver damage. -
Key words:
- Hemophagocytic syndrome /
- Ferritin /
- Iron metabolism /
- Cytokines /
- Liver function
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图 1 实验组和对照组铁代谢相关指标的对比
A:HLH组和对照组铁调素比较;B:HLH组和对照组铁蛋白比较;C:HLH组和对照组总铁结合力比较;D:HLH组和对照组不饱和铁结合力比较;E:HLH组和对照组血清铁比较;F:HLH组和对照组铁饱和度比较;G:HLH组和对照组转铁蛋白比较;H:实验组和对照组sTfR比较;I:HLH组和对照组骨髓外铁染色比较;J:HLH组和对照组幼红细胞铁染色比较;*P < 0.05。
Figure 1. Comparison of iron metabolism-related indexes between the experimental group and the control group
图 2 实验组和对照组细胞因子的对比
A:HLH组和对照组IL-4比较;B:HLH组和对照组IL-6比较;C:HLH组和对照组IL-22比较;D:HLH组和对照组IL-17F比较;E:HLH组和对照组TNF-β比较;F:HLH组和对照组IL-17A比较;G:HLH组和对照组TNF-ɑ比较;H:HLH组和对照组INF-γ比较;I:HLH组和对照组IL-2比较;J:HLH组和对照组IL-5比较;K:HLH组和对照组IL-1β比较;L:HLH组和对照组IL-12P70比较;M:HLH组和对照组IL-8比较;N:HLH组和对照组IL-10比较;*P < 0.05。
Figure 2. Comparison of cytokines between the experimental group and the control group
表 1 实验组和对照组性别、年龄对比[($\bar x \pm s $)/n(%)]
Table 1. Comparison of gender and age between the experimental group and the control group[($\bar x \pm s $)/n(%)]
项目 HLH组 (n=41) 对照组 (n=41) t/χ2 P 年龄(岁) 49.44±15.90 43.61±18.76 − 1.5174 0.133 男 20(48.8) 22(53.7) 0.195 0.659 女 21(51.2) 19(46.3) -
[1] Lehrer H,Scigliano E,Chan A. Central nervous system hemophagocytic lymphohistiocytosis (CNS-HLH) from leptomeningeal anaplastic large cell lymphoma : Mild clinical neurologic syndrome with extensive multifocal white matter disease[J]. Clin Neuroradiol,2021,31(3): 881-883. [2] Khan H H,Ansar I,Kontos N,et al. Report of a fatal case of hemophagocytic lymphohistiocytosis syndrome and a review of the literature[J]. Cureus,2020,12(12):e12049. [3] Birndt S,Schenk T,Heinevetter B,et al. Hemophagocytic lymphohistiocytosis in adults: Collaborative analysis of 137 cases of a nationwide German registry[J]. J Cancer Res Clin Oncol,2020,146(4):1065-1077. doi: 10.1007/s00432-020-03139-4 [4] Boshuizen M,Binnekade J M,Nota B,et al. Potential of parameters of iron metabolism for the diagnosis of anemia of inflammation in the critically ill[J]. Transfus Med Hemother,2020,47(1):61-67. doi: 10.1159/000497123 [5] Nabergoj M,Marinova M,Binotto G,et al. Diagnostic and prognostic value of low percentage of glycosylated ferritin in acquired hemophagocytic lymphohistiocytosis: A single-center study[J]. Int J Lab Hematol,2017,39(6):620-624. doi: 10.1111/ijlh.12713 [6] Kallianpur A R,Wen W,Erwin A L,et al. Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy[J]. PLoS One,2020,15(10):e239758. [7] Lachmann G,Knaak C,Vorderwulbecke G,et al. Hyperferritinemia in critically ill patients[J]. Crit Care Med,2020,48(4):459-465. doi: 10.1097/CCM.0000000000004131 [8] Ten K J,Drenth J P,Kahn M F,et al. Iron saturation of serum ferritin in patients with adult onset Still's disease[J]. J Rheumatol,2001,28(10):2213-2215. [9] Patel S,Monemian S,Khalid A,et al. Iron Deficiency anemia in adult onset still's disease with a serum ferritin of 26,387 mug/L[J]. Anemia,2011,12(5):184748. [10] Henter J I,Horne A,Arico M,et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis[J]. Pediatr Blood Cancer,2007,48(2):124-131. doi: 10.1002/pbc.21039 [11] Zhang X,Wang J,Tan Y,et al. Nanobodies in cytokine-mediated immunotherapy and immunoimaging (Review)[J]. Int J Mol Med,2024,53(2):2023-5336. [12] Zhang H Q,Yang S W,Fu Y C,et al. Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis[J]. Immunol Res,2022,70(5):566-577. doi: 10.1007/s12026-022-09285-w [13] 徐晓军,汤永民,赵宁,等. Th1/Th2细胞因子谱在儿童噬血细胞综合征诊断中的意义[J]. 中华儿科杂志,2011,49(9):685-689. [14] Liu Y,Chen L. Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients[J]. World J Clin Cases,2024,12(23):5374-5381. doi: 10.12998/wjcc.v12.i23.5374 [15] 王宇,卫青,李硕,等. 炎性细胞因子检测在噬血细胞综合征诊断中的应用[J]. 临床内科杂志,2014,31(9):637-639. [16] 胡迎,王松咪,张艾,等. 多种细胞因子检测在儿童噬血细胞综合征诊断中的意义[J]. 检验医学与临床,2018,15(19):2880-2883. [17] Cao Y,Huang Y. Systematic analysis of liver failure accompanied with hemophagocytic syndrome in adults[J]. Zhonghua Gan Zang Bing Za Zhi,2023,31(10):1056-1062. [18] Li J,Wang Q,Zheng W,et al. Hemophagocytic lymphohistiocytosis: Clinical analysis of 103 adult patients[J]. Medicine (Baltimore),2014,93(2):100-105. [19] Griffin G,Shenoi S,Hughes G C. Hemophagocytic lymphohistiocytosis: An update on pathogenesis,diagnosis,and therapy[J]. Best Pract Res Clin Rheumatol,2020,34(4):101515. doi: 10.1016/j.berh.2020.101515 [20] Ponnatt T S,Lilley C M,Mirza K M. Hemophagocytic lymphohistiocytosis[J]. Arch Pathol Lab Med,2022,146(4):507-519. doi: 10.5858/arpa.2020-0802-RA [21] Pan J,Liao Y,Huang Q,et al. Associations between serum ferritin,iron,and liver transaminases in adolescents: A large cross-sectional study[J]. Nutr Hosp,2023,40(5):949-959. [22] Jing X,Wang W,He X,et al. HIF-2alpha/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration[J]. J Orthop Translat,2024,46(21):65-78.