原发免疫性血小板减少症患者MDSCs、B7-H2、Treg/Th17水平对疗效的预测价值

Predictive Value of MDSCs, B7-H2 and Treg/Th17 Levels for Therapeutic Efficacy in Patients with Primary Immune Thrombocytopenia

摘要

目的 探究原发免疫性血小板减少症（immune thrombocytopenia，ITP）患者髓源性抑制性细胞（myeloid-derived suppressor cells，MDSCs）、可诱导共刺激分子配体（B7 Homolog 2，B7-H2）与调节性T细胞（regulatory T cell，Treg）/辅助性T细胞17（T helper 17 cell，Th17）免疫失衡的相关性，并分析其对疗效的预测价值。方法 选取2020年1月至2025年1月株洲市中心医院收治的191例ITP患者（ITP组，建模集）进行前瞻性研究，按照1:1另选同期191例健康体检者作为对照组。比较两组MDSCs、B7-H2、Treg/Th17、骨髓巨核细胞形态及血小板相关抗体血小板相关免疫球蛋白G（platelet-associated Immunoglobulin G，PAIgG）、血小板相关免疫球蛋白A（platelet-associated Immunoglobulin A，PAIgA）、血小板相关免疫球蛋白M（platelet-associated Immunoglobulin M，PAIgM）。分析MDSCs、B7-H2、Treg/Th17对ITP疗效的影响，并分析其对疗效的预测价值。另选取2025年1月至2025年12月52例ITP患者作为独立外部验证集，对MDSCs、B7-H2联合Treg/Th17预测价值进行验证。结果 ITP组MDSCs、Treg、Treg/Th17低于对照组，B7-H2、Th17高于对照组（P < 0.05）；总有效亚组治疗后MDSCs、Treg/Th17高于无效亚组，B7-H2低于无效亚组（P < 0.05）；治疗前MDSCs、B7-H2、Treg/Th17均是ITP疗效的相关影响因素（P < 0.05）；治疗前MDSCs、Treg/Th17与疗效呈正相关（P_趋势 < 0.05，P_非线性>0.05），B7-H2与疗效呈负相关（P_趋势 < 0.05，P_非线性 > 0.05）；联合的AUC值（0.898）显著大于单独的MDSCs（0.764）、B7-H2（0.739）、Treg/Th17（0.761）。验证集中，联合预测模型在验证队列中的AUC与研究队列接近。Pearson相关性分析显示，颗粒型巨核细胞与MDSCs、Treg/Th17呈负相关，与B7-H2呈正相关（P < 0.001）；产板型巨核细胞与MDSCs、Treg/Th17呈正相关，与B7-H2呈负相关（P < 0.001）；PAIgG、PAIgA、PAIgM均与MDSCs、Treg/Th17呈负相关，与B7-H2呈正相关（P < 0.001）。结论 ITP患者MDSCs、B7-H2与Treg/Th17密切相关，这些指标的检测对疗效具有预测价值，联合分析可提高预测效能。

Abstract

Objective To investigate the correlation between myeloid-derived suppressor cells (MDSCs), B7 Homolog 2 (B7-H2), and regulatory T cell (Treg)/T helper 17 cell (Th17) immune imbalance in patients with primary immune thrombocytopenia (ITP), and to analyze their predictive value for therapeutic efficacy. Methods A total of 191 ITP patients (ITP group, modeling set) admitted to Zhuzhou Central Hospital from January 2020 to January 2025 were selected for prospective study, and another 191 healthy subjects in the same period were selected in a 1:1 ratio as the control group. MDSCs, B7-H2, Treg/Th17, bone marrow megakaryocyte morphology and platelet-associated antibodies [platelet-associated Immunoglobulin G (PAIgG), platelet-associated Immunoglobulin A (PAIgA), platelet-associated Immunoglobulin M (PAIgM)] were compared between the two groups. The effects of MDSCs, B7-H2 and Treg/Th17 on ITP treatment efficacy and their predictive value were analyzed. In addition, another 52 ITP patients from January 2025 to December 2025 were selected as independent external validation set to validate the combined predictive value of MDSCs, B7-H2, and Treg/Th17. Results The ITP group showed lower MDSCs, Treg, and Treg/Th17 ratio, and higher B7-H2 and Th17 levels compared to the control group (P < 0.05). After treatment, the effective subgroup had higher MDSCs and Treg/Th17 ratio, and lower B7-H2 than the ineffective subgroup (P < 0.05). Before treatment, MDSCs, B7-H2, and Treg/Th17 ratio were all related factors affecting the efficacy of ITP treatment (P < 0.05). Before treatment, MDSCs and Treg/Th17 showed a positive correlation with efficacy (P_trend <0.05, P_nonlinea>0.05), while B7-H2 showed a negative correlation with efficacy (P_trend < 0.05, P_nonlinea>0.05). The combined AUC value (0.898) was significantly greater than that of MDSCs alone (0.764), B7-H2 alone (0.739), and Treg/Th17 alone (0.761). In the validation set, the AUC of the combined prediction model was similar to that in the training set. Pearson correlation analysis showed that granular megakaryocytes were negatively correlated with MDSCs and Treg/Th17, and positively correlated with B7-H2 (P < 0.001). Plate-forming megakaryocytes were positively correlated with MDSCs and Treg/Th17, and negatively correlated with B7-H2 (P < 0.001). PAIgG, PAIgA and PAIgM were negatively correlated with MDSCs and Treg/Th17, and positively correlated with B7-H2 (P < 0.001). Conclusion MDSCs and b7-h2 in ITP patients are closely related to Treg/Th17. The detection of these indicators has predictive value for curative effect, and combined analysis can improve the predictive efficiency.

关键词

原发免疫性血小板减少症 / 髓源性抑制性细胞 / 可诱导共刺激分子配体 / 调节性T细胞 / 辅助性T细胞17 / 预测价值

Key words

Primary immune thrombocytopenia / Myeloid-derived suppressor cells / B7 homolog 2 / Regulatory T cells / T helper cell 17 / Predictive value

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基金资助

湖南省自然科学基金(2024JJ5327)