Ni Jing, Zou Dongmei, Cao Yaofang, Liu Yan, Fang Fang, Chang Xiaoli, Hui Wuhan, Guo Yixian, Hu Ronghua, Zhao Hong, Su Li, Sun Wanling
Department of Hematology, XuanWu hospital, Capital Medical University, Beijing 100053, China.
Department of Hematology, XuanWu hospital, Capital Medical University, Beijing 100053, China.
Cytokine. 2025 Oct;194:157000. doi: 10.1016/j.cyto.2025.157000. Epub 2025 Jul 24.
Hemophagocytic lymphohistiocytosis (HLH) is generally recognized as a rapidly progressive syndrome of excessive immune activation and a cytokine storm. Diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup of non-Hodgkin lymphoma, represents a common trigger of HLH. Due to the overlap in clinical manifestations between HLH and the underlying lymphoma, it is challenging to identify secondary HLH (sHLH) in DLBCL patients early. To elucidate the differences between DLBCL with HLH (DLBCL-HLH) and DLBCL without HLH (DLBCL-non-HLH), we comparatively analyzed the clinical parameters and serum cytokines in patients with DLBCL-HLH or DLBCL-non-HLH. Serum levels of interleukin (IL)-2, IL-4, IL-6, IL-8, IL-1β, IL-17 A, IL-10, IL-12P70, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IFN-α in 8 patients with DLBCL-HLH and 51 patients with DLBCL-non-HLH were measured by cytometric bead array. Compared to patients with DLBCL-non-HLH, those with DLBCL-HLH had significantly elevated lactate dehydrogenase (LDH) levels, increased serum ferritin levels, raised liver transaminases, a higher proportion of lymphoma bone marrow involvement, significantly decreased albumin levels, and reduced peripheral blood cell counts. Both in patients with DLBCL-HLH and those with DLBCL-non-HLH, serum levels of IL-6 and IL-10 were elevated. However, these cytokine levels were significantly higher among patients with DLBCL-HLH. In particular, when the level of IL-10 > 180.70 pg/ml, the sensitivity and specificity of the diagnosis of DLBCL-HLH were 87.50 % and 96.08 %, respectively. Interestingly, in patients with DLBCL-non-HLH, we observed that IL-10 positively correlated with serum ferritin levels (r = 0.768, P < 0.001), and negatively correlated with hemoglobin concentrations and platelet counts (r = -0.388, P = 0.005; r = -0.412, P = 0.003). Taken together, our results revealed that elevated serum IL-10 levels are significantly associated with sHLH in DLBCL patients, suggesting its potential as a diagnostic biomarker. High serum IL-10 levels, combined with bone marrow involvement by lymphoma, high lactate dehydrogenase, decreased albumin levels, and HLH diagnostic criteria such as increased ferritin levels and cytopenia, might boost the early identification of DLBCL-HLH.
噬血细胞性淋巴组织细胞增生症（HLH）通常被认为是一种由过度免疫激活和细胞因子风暴引起的快速进展性综合征。弥漫性大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤的一个常见亚组，是HLH的常见诱因。由于HLH与潜在淋巴瘤的临床表现存在重叠，早期识别DLBCL患者中的继发性HLH（sHLH）具有挑战性。为了阐明伴有HLH的DLBCL（DLBCL-HLH）与不伴有HLH的DLBCL（DLBCL-non-HLH）之间的差异，我们对DLBCL-HLH或DLBCL-non-HLH患者的临床参数和血清细胞因子进行了比较分析。通过细胞计数珠阵列检测了8例DLBCL-HLH患者和51例DLBCL-non-HLH患者血清中的白细胞介素（IL）-2、IL-4、IL-6、IL-8、IL-1β、IL-17A、IL-10、IL-12P70、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和IFN-α水平。与DLBCL-non-HLH患者相比，DLBCL-HLH患者的乳酸脱氢酶（LDH）水平显著升高，血清铁蛋白水平升高，肝转氨酶升高，淋巴瘤骨髓受累比例更高，白蛋白水平显著降低，外周血细胞计数减少。DLBCL-HLH患者和DLBCL-non-HLH患者的血清IL-6和IL-10水平均升高。然而，DLBCL-HLH患者中的这些细胞因子水平显著更高。特别是，当IL-10水平>180.70 pg/ml时，DLBCL-HLH诊断的敏感性和特异性分别为87.50%和96.08%。有趣的是，在DLBCL-non-HLH患者中，我们观察到IL-10与血清铁蛋白水平呈正相关（r = 0.768，P < 0.001），与血红蛋白浓度和血小板计数呈负相关（r = -0.388，P = 0.005；r = -0.412，P = 0.003）。综上所述，我们的结果表明，血清IL-10水平升高与DLBCL患者的sHLH显著相关，提示其作为诊断生物标志物的潜力。高血清IL-10水平，结合淋巴瘤骨髓受累、高乳酸脱氢酶、白蛋白水平降低以及铁蛋白水平升高和血细胞减少等HLH诊断标准，可能有助于早期识别DLBCL-HLH。
