Predictive Value of MDSCs，B7-H2 and Treg/Th17 Levels for Therapeutic Efficacy in Patients with Primary Immune Thrombocytopenia
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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月一2025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～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、Treg/Th17水平降低，B7-H2水平升高，MDSCs与Treg/Th17呈正相关，B7-H2与Treg/Th17呈负相关，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。 -
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
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 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 （Ptrend <0.05, Pnonlinea>0.05）, while B7-H2 showed a negative correlation with efficacy （Ptrend < 0.05, Pnonlinea>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 In ITP patients, MDSCs and Treg/Th17 ratio are decreased, while the level of B7-H2 is elevated. There is a positive correlation between MDSCs and Treg/Th17, and a negative correlation between B7-H2 and Treg/Th17. Detection of these indicators has predictive value for treatment efficacy, and combined analysis can improve the predictive performance. -
图 1 两组Treg（CD4+CD25+Foxp3+）流式细胞分析图
A：有核细胞散点图；B：活细胞门；C：显示所有有核细胞；D：显示有核细胞门并圈中CD3+CD4细胞；E：显示所有CD3+CD4细胞，圈中CD25+FoxP3，为Treg细胞。
Figure 1. Flow cytometric analysis of Treg in the two groups （CD4+CD25+Foxp3+）
图 2 两组Th17（CD3+CD8-IL-17+）流式细胞分析图
A：显示有核细胞门并圈中CD3+CD8-细胞；B：显示所有CD3+CD8-细胞，IL-17A+为1L-17阳性细胞。
Figure 2. Flow cytometric analysis of Th17 （CD3+CD8-IL-17+） in the two groups
图 3 ITP组治疗前MDSCs、B7-H2与Treg/Th17免疫失衡相关性
A：MDSCs与Treg相关性；B：MDSCs与Th17相关性；C：MDSCs与Treg/Th17相关性；D：B7-H2与Treg相关性；E：B7-H2与Th17相关性；F：B7-H2与Treg/Th17相关性。
Figure 3. Correlation of MDSCs，B7-H2 with Treg/Th17 immune imbalance before treatment in ITP group
图 4 治疗前MDSCs、B7-H2、Treg/Th17与疗效的相关性
A：治疗前MDSCs与疗效的相关性；B：治疗前Treg/Th17与疗效的相关性；C：治疗前B7-H2与疗效的相关性。
Figure 4. Correlation of pre-treatment MDSCs，B7-H2，Treg/Th17 with treatment efficacy
图 5 治疗前MDSCs、B7-H2、Treg/Th17预测疗效的ROC曲线
Figure 5. ROC curves of pre-treatment MDSCs，B7-H2，and Treg/Th17 for predicting treatment efficacy
表 1 两组一般资料比较[（$ \bar x \pm s $）/n（%）]
Table 1. Comparison of general data between the two groups [（$ \bar x \pm s $）/n（%）]
组别 n 性别 年龄（岁） 体质量指数（kg/m2） 男 女 ITP组 191 25（13.09） 166（86.91） 44.32 ± 6.22 24.11 ± 2.74 对照组 191 31（16.23） 160（83.77） 43.26 ± 5.09 23.88 ± 3.02 t/χ2 0.753 1.823 0.780 P 0.385 0.069 0.436 
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表 2 建模集与验证集患者的一般资料比较[（$ \bar x \pm s $）/n（%）]
Table 2. Comparison of general data between training set and the validation set [（$ \bar x \pm s $）/ n （%）]
组别 n 性别 年龄（岁） 体质量
指数
（kg/m2）基线血
小板
（×109/L）巨核细胞
总数
（个/全片）原始+
幼稚型
（%）颗粒型
（%）产板型
（%）裸核型
（%）PAIgG
（ng/mL）PAIgA
（ng/mL）PAIgM
（ng/mL）男 女 建模集 191 25（13.09） 166（86.91） 44.32±6.22 24.11±2.74 16.62±5.35 86.35±15.42 12.58±3.61 65.37±10.25 8.42±2.75 13.63±4.28 68.54±15.32 32.45±8.66 45.62±11.37 验证集 52 11（21.15） 41（78.85） 45.20±7.14 24.02±2.25 17.11±4.98 84.99±13.20 11.86±3.05 63.99±9.86 8.12±2.63 12.57±3.94 66.96±14.29 30.99±9.14 42.23±10.26 t/χ2 2.107 −0.876 0.218 −0.594 0.581 1.316 0.868 0.704 1.610 0.669 1.065 1.945 P 0.147 0.382 0.828 0.553 0.562 0.190 0.386 0.482 0.109 0.504 0.288 0.053
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表 3 ITP组与对照组MDSCs、B7-H2、Treg/Th17比较（$ \bar x \pm s $）
Table 3. Comparison of MDSCs，B7-H2，Treg/Th17 between ITP group and control group （$ \bar x \pm s $）
组别 n MDSCs（%） B7-H2（ng/mL） Treg（%） Th17（%） Treg/Th17 ITP组 191 0.82 ± 0.27 31.94 ± 5.13 4.78 ± 0.92 2.04 ± 0.45 2.34 ± 0.66 对照组 191 1.76 ± 0.40 20.56 ± 3.78 7.20 ± 1.85 0.96 ± 0.30 7.50 ± 0.92 t 26.919 24.681 16.187 27.598 62.983 P <0.001* <0.001* <0.001* <0.001* <0.001* *P < 0.05。
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表 4 ITP患者治疗前后MDSCs、B7-H2、Treg/Th17比较（$ \bar x \pm s $）
Table 4. Comparison of MDSCs，B7-H2，Treg/Th17 in ITP patients before and after treatment （$ \bar x \pm s $）
组别 n MDSCs（%） B7-H2（ng/mL） Treg/Th17 总有效 154 治疗前 0.89 ± 0.27 30.33 ± 5.02 2.45 ± 0.61 治疗后 1.45 ± 0.43∆ 25.10 ± 4.63∆ 5.47 ± 0.85∆ t 13.687 9.504 35.821 P <0.001* <0.001* <0.001* 无效 37 治疗前 0.53 ± 0.15 38.64 ± 4.99 1.88 ± 0.60 治疗后 0.56 ± 0.18 37.25 ± 5.04 1.95 ± 0.66 t 0.779 1.192 0.477 P 0.439 0.237 0.635 *P < 0.001；与无效比较，∆P < 0.05。
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表 5 治疗前MDSCs、B7-H2、Treg/Th17对ITP疗效的影响
Table 5. Effect of pre-treatment MDSCs，B7-H2，and Treg/Th17 on ITP treatment efficacy
自变量 β SE Wald χ2 OR 95%CI P 下限 上限 MDSCs −0.672 0.256 6.895 0.511 0.289 0.902 0.009* B7-H2 0.455 0.144 9.934 1.576 1.326 1.874 0.002* Treg/Th17 −0.537 0.205 6.868 0.584 0.379 0.901 0.009* 常数项 1.914 0.482 15.768 − − − <0.001* *P < 0.05。
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表 6 PSM后两组的临床资料比较
Table 6. Comparison of clinical data between the two groups after PSM
组别 n 性别 年龄（岁） 病程（月） 体质量指数（kg/m2） 基线血小板（×10⁹/L） 男 女 总有效组 37 18（48.65） 19（51.35） 44.32 ± 6.22 5.62 ± 1.79 23.99 ± 2.61 25.89 ± 6.35 无效组 37 17（45.95） 20（54.05） 45.20 ± 7.14 5.70 ± 1.58 24.05 ± 2.38 27.03 ± 7.19 t/χ2 0.054 0.565 0.204 0.103 0.723 P 0.816 0.574 0.839 0.918 0.472
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表 7 匹配后Logistic回归结果
Table 7. Results of Logistic regression after matching
自变量 OR 95%CI P 下限 上限 MDSCs 0.656 0.463 0.930 0.018* B7-H2 1.697 1.250 2.304 <0.001* Treg/Th17 0.627 0.404 0.972 0.037* *P < 0.05。
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表 8 治疗前MDSCs、B7-H2、Treg/Th17预测疗效的价值
Table 8. Predictive values of pre-treatment MDSCs，B7-H2，and Treg/Th17 for treatment efficacy
指标 AUC 95%CI cut-off值 敏感度（%） 特异度（%） P MDSCs 0.764 0.697～0.822 0.63 81.08 66.88 <0.001* B7-H2 0.739 0.671～0.800 35.18 75.68 68.83 <0.001* Treg/Th17 0.761 0.694～0.820 2.06 67.57 79.87 <0.001* 联合 0.898 0.846～0.937 86.49 83.77 <0.001* *P < 0.05。
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表 9 骨髓巨核细胞、血小板抗体与MDSCs、B7-H2、Treg/Th17相关性（r值）
Table 9. Correlation of bone marrow megakaryocytes and platelet antibodies with MDSCs，B7-H2 and Treg/Th17 （r value）
指标 MDSCs B7-H2 Treg/Th17 颗粒型巨核细胞 −0.685* 0.712* −0.703* 产板型巨核细胞 0.724* −0.695* 0.731* 裸核型巨核细胞 0.315* −0.332* 0.326* PAIgG −0.673* 0.708* −0.689* PAIgA −0.592* 0.635* −0.614* PAIgM −0.625* 0.651* −0.638* *P < 0.05。
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