淋巴细胞亚群和活化表型在非霍奇金淋巴瘤相关噬血细胞综合征中的表达和诊断价值

Expression and diagnostic value of lymphocyte subsets and activation status in non-Hodgkin's lymphoma-associated hemophagocytic lymphohistiocytosis

目的探讨外周血淋巴细胞和功能活化状态在非霍奇金淋巴瘤相关噬血细胞综合征(NHL-HLH)中的表达和诊断价值。方法回顾性分析江苏省人民医院2022年9月至2023年9月收治的30例初诊NHL-HLH患者的临床资料,流式细胞术检测淋巴细胞亚群和功能活化指标。选取同期在本院接受治疗的40例初诊NHL且完善淋巴细胞和功能活化指标的患者作为对照组。比较两组淋巴细胞计数和活化指标的差异。运用受试者工作特征曲线和Logistic回归分析识别NHL-HLH的风险因素。结果NHL-HLH组中,T细胞淋巴瘤12例,B细胞淋巴瘤18例。对照组中,T细胞淋巴瘤19例,B细胞淋巴瘤21例。比较两组发现,NHL-HLH组的CD3^(+)T、CD4^(+)T、CD8^(+)T、NK细胞绝对计数低于对照组(P值均<0.01)。CD8^(+)T细胞表面CD38和HLA-DR表达水平高于对照组(CD8^(+)CD38^(+)/CD8^(+)T细胞中位数:57.4%比21.5%,P<0.001;CD8^(+)HLA-DR^(+)/CD8^(+)T细胞中位数49.7%比33.5%,P=0.028);此外,CD4^(+)T细胞和CD8^(+)T细胞上第二受体信号CD28表达增加(P<0.01)。统计分析表明NK细胞绝对计数≤72.0个/μl、CD4^(+)CD28^(+)/CD4^(+)T细胞>94.2%和CD8^(+)CD38^(+)/CD8^(+)T细胞>38.4%是预测NHL-HLH发生的危险因素,回归模型的敏感度和特异度分别为86.7%和86.1%,曲线下面积达0.94(P<0.001)。结论NHL-HLH发生时T淋巴细胞计数减低,而T细胞功能呈活化状态。NK细胞绝对计数≤72.0个/μl、CD4^(+)CD28^(+)/CD4^(+)T细胞>94.2%和CD8^(+)CD38^(+)/CD8^(+)T细胞>38.4%是预测NHL-HLH发生的危险因素,可协助临床早期诊疗。

Objective To determine the expression and diagnostic value of peripheral blood lymphocytes and functional activation status in non-Hodgkin lymphoma with hemophagocytic lymphohistiocytosis(NHL-HLH).Methods We retrospectively analyzed clinical data from 30 newly diagnosed NHL-HLH patients admitted to Jiangsu Province Hospital from September 2022 to September 2023.We assessed peripheral blood lymphocytes and activation status by flow cytometry.Forty newly diagnosed patients with NHL who received treatment at our hospital during the same period and had lymphocyte and functional activation indexes were selected as the control group.The differences in relative and absolute lymphocyte counts and functional activation indexes between the two groups were compared.The optimal cutoff values for continuous variables were calculated from the receiver operating characteristic curve and logistic regression analysis was used to evaluate the risk factors in NHL patients with HLH.Results A total of 30 NHL-HLH patients were evaluated,including 12 T-cell lymphoma and 18 B-cell lymphoma patients.Forty individuals were in the control group,which included 19 T-cell lymphoma and 21 B-cell lymphoma patients.The absolute counts of CD3^(+)T,CD4^(+)T,CD8^(+)T,and NK cells,along with the relative count of NK cells,were significantly lower in the HLH group compared with that in the control group(all P values<0.01).The expression of CD38 and HLA-DR on CD8^(+)T-cell activated subgroups was significantly higher in the NHL-HLH group compared with that in the control group(CD8^(+)CD38^(+)/CD8^(+)T expression median:57.4%vs 21.5%,P<0.001;CD8^(+)CD38^(+)/CD8^(+)T expression median:49.7%vs 33.5%,P=0.028,respectively).In addition,CD28 expression on CD4^(+)and CD8^(+)T cells was significantly higher in NHL-HLH patients(P<0.01).ROC curve and multivariate logistic regression analyses revealed that absolute NK cell count≤72.0 cells/μl,CD4^(+)CD28^(+)/CD4^(+)T>94.2%,and CD8^(+)CD28^(+)/CD8^(+)T>38.4%were risk factors for predicting the occurrence of NHL-HLH patients.The sensitivity and specificity of the regression model were 86.7%and 86.1%,respectively,with an area under the curve of 0.94(P<0.001).Conclusions In NHL patients with HLH,there was a significant reduction in the absolute number of peripheral blood lymphocyte subpopulations,whereas T-cell function was notably activated.Specifically,absolute counts of NK cells≤72.0 cells/μl,CD4^(+)CD28^(+)/CD4^(+)T>94.2%,and CD8^(+)CD28^(+)/CD8^(+)T>38.4%were identified as risk factors for predicting the development of NHL-HLH patients.This will assist in early clinical diagnosis and treatment.