[1]田秋霞a,许元英b,毛怀凤a,等.免疫性血小板减少性紫癜患者血清sPD1 和sPD-L1 表达及临床意义[J].现代检验医学杂志,2023,38(04):89-93+109.[doi:10.3969/j.issn.1671-7414.2023.04.016]
　TIAN Qiuxiaa,XU Yuanyingb,MAO Huaifenga,et al.Expression and Clinical Significance of Serum sPD1 and sPD-L1 in Patients with Immune Thrombocytopenic Purpura[J].Journal of Modern Laboratory Medicine,2023,38(04):89-93+109.[doi:10.3969/j.issn.1671-7414.2023.04.016]
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免疫性血小板减少性紫癜患者血清sPD1 和sPD-L1 表达及临床意义()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年04期
页码:
89-93+109
栏目:
论著
出版日期:
2023-07-15

文章信息/Info

Title:
Expression and Clinical Significance of Serum sPD1 and sPD-L1 in Patients with Immune Thrombocytopenic Purpura
文章编号:
1671-7414（2023）04-089-06
作者:
田秋霞a; 许元英b; 毛怀凤a; 王 婷a; 洪 亮a
（四川省阿坝藏族羌族自治州人民医院a. 检验科；b. 血液科 ，四川阿坝州 624000）
Author(s):
TIAN Qiuxiaa;  XU Yuanyingb;  MAO Huaifenga;  WANG Tinga;  HONG Lianga
（a. Department of Clinical Laboratory；b. Department of Blood Specialty, People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, Sichuan Aba Prefecture 624000, China）
关键词:
免疫性血小板减少性紫癜; 可溶性程序性死亡受体1; 可溶性程序性死亡配体1
分类号:
R554.6；R392.11
DOI:
10.3969/j.issn.1671-7414.2023.04.016
文献标志码:
A
摘要:
目的　探讨免疫性血小板减少性紫癜(immune thrombocytopenic purpura，ITP) 患者血清可溶性程序性死亡受体1(soluble programmed death receptor 1，sPD-1) 和可溶性程序性死亡配体1(soluble programmed death ligand 1，sPD-L1)水平及临床意义。方法　选取2019 年1 月～ 2021 年1 月期间四川省阿坝藏族羌族自治州人民医院收治的ITP 患者114例为ITP 组，根据治疗疗效将ITP 组患者分为治疗有反应组（n=80）和治疗无反应组（n=34）。选取同期42 例在该院化疗后骨髓抑制血小板减少患者为病例对照组，同期健康体检的健康人50 例为健康对照组。采用酶联免疫吸附实验检测血清中sPD-1 和sPD-L1 水平。比较各组血清sPD-1，sPD-L1，血小板计数（PLT）和平均血小板体积（MPV）水平。相关性分析采用Pearson 相关分析。多因素Logistic 回归分析影响ITP 治疗疗效的因素。受试者工作曲线分析血清sPD-1，sPD-L1，MPV 及联合模型对ITP 治疗疗效的预测价值。结果　ITP 组血清sPD-1（124.47±31.26 ng/L），sPD-L1（85.74±13.57 ng/L） 及MPV（9.70±1.25 fl） 高于病例对照组（84.63±14.26 ng/L，64.85±11.20 ng/L，6.53±1.36fl） 和健康对照组(63.20±10.15 ng/L，51.07±10.16 ng/L，7.88±1.45fl)，PLT[（9.02±1.04）×109/L] 低于病例对照组[（84.96±10.24）×109/L] 和健康对照组[（179.82±21.35）×109/L]，差异均有统计学意义(t=12.617，20.661；13.247，23.388；18.770，11.468；5.824，124.03，均P<0.05)。ITP 患者血清sPD-1，sPD-L1 与PLT 呈明显负相关(r=-0.745，-0.810，均P<0.05)，与MPV 呈明显正相关(r=0.740，0.796，均P<0.05)。治疗无反应组血清sPD-1（148.00±31.70 ng/L），sPD-L1（110.42±11.69 ng/L）水平高于治疗有反应组（114.47±30.66 ng/L，75.25±12.34 ng/L），PLT[（6.13±0.86 ）×109/L]，MPV（8.87±1.21 fL）水平低于治疗有反应组[（10.34±1.07）×109/L，10.05±1.27 fl]，差异具有统计学意义（t=5.288，14.137，20.307，4.601，均P<0.05）。MPV（OR=0.751，95%CI=0.597 ～ 0.945），血清sPD-1（OR=1.278，95%CI =1.149 ～ 1.420）和sPD-L1（OR=1.670，95%CI =1.114 ～ 1.448）是影响ITP 治疗疗效的独立因素。联合模型对ITP 治疗疗效预测的敏感度和特异度分别为0.752，0.801。联合模型对ITP 治疗疗效预测的曲线下面积为0.849(95%CI:0.811 ～ 0.886)，显著高于MPV，sPD-1 和sPD-L1 单一指标检测0.760(95%CI:0.719 ～ 0.801)，0.699(95%CI:0.660 ～ 0.737)，0.747(95%CI:0.709 ～ 0.785)，差异具有统计学意义(Z=3.029，3.690，2.789，均P < 0.05)。结论　ITP 患者血清sPD-1 和sPD-L1 水平升高，是影响ITP 治疗疗效的危险因素，血清sPD-1，sPD-L1 和MPV 联合模型对ITP 治疗疗效具有较高的诊断价值。
Abstract:
Objective　To investigate the serum levels of soluble programmed death receptor 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in patients with immune thrombocytopenic purpura (ITP) and their clinical significance. Methods　114 ITP patients admitted to People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture from January 2019 to January 2021 were selected as ITP group. According to the therapeutic effect, the patients in the ITP group were divided into two groups: the treatment response group(n=80) and the treatment non response group(n=34).42 patients with myelosuppression and thrombocytopenia after chemotherapy in the hospital in the same period were selected as case control group, and 50 healthy people in the same period were selected as health control group. The levels of sPD-1 and sPD-L1 in serum were detected by enzyme-linked immunosorbent assay. Compare the levels of serum sPD-1, sPD-L1, platelet count (PLT), and mean platelet volume (MPV) in each group. Pearson correlation analysis was used for correlation analysis. Multivariate logistic regression analysis was used to analyze the factors influencing the therapeutic effect of ITP. The predictive value of serum sPD-1, sPD-L1, MPV, and the combined model on the efficacy of ITP was analyzed by the receiver operating curve. Results　The serum levels of sPD-1 (124.47 ± 31.26 ng/L), sPD-L1 (85.74 ± 13.57 ng/L) and MPV （9.70±1.25 fl）in the ITP group were significantly higher than those in the case control group（84.63±14.26 ng/L，64.85±11.20 ng/L，6.53±1.36fl） and healthy control group(63.20±10.15 ng/L，51.07±10.16 ng/L，7.88±1.45fl) and PLT[（9.02±1.04)×109/L ]was significantly lower than those in the case control group[（84.96±10.24）×109/L] and healthy control group[（179.82±21.35）×109/L]，the differences were statistically significant (t=12.6174, 20.661; 13.247, 23.388; 18.770, 11.468; 5.824, 124.037, all P<0.05).Serum sPD-1 and sPD-L1 in ITP patients were significantly negatively correlated with PLT (r=-0.745，-0.810，all P<0.05), and significantly positively correlated with MPV (r=0.740, 0.796, all P<0.05). The levels of serum sPD-1 (148.00 ± 31.70 ng/L ) and sPD-L1 (110.42 ± 11.69 ng/L) in the treatment non response group were higher than those in the treatment response group （114.47 ± 30.66 ng/L, 75.25 ± 12.34 ng/L）, and PLT[ (6.13 ± 0.86 )× 109/L], MPV (8.87± 1.21 fl) levels were lower than those in the treatment response group（[ 10.34±1.07）×109/L，10.05±1.27 fl], the difference was statistically significant (t=5.288, 14.137，20.307, 4.601, all P<0.05).MPV (OR=0.751, 95% CI: 0.597 ～0.945), serum sPD-1 (OR=1.278, 95% CI: 1.149 ～1.420), and sPD-L1 (OR=1.670, 95% CI: 1.114 ～ 1.448) were independent factors affecting the efficacy of ITP treatment. The sensitivity and specificity of the combined model for predicting the efficacy of ITP were 0.752 and 0.801, respectively. The area under the curve of the combined model to predict the efficacy of ITP treatment was 0.849(95%CI:0.811 ～ 0.886), significantly higher than that of MPV, sPD-1, sPD-L1 single index detection 0.760(95%CI:0.719 ～ 0.801)，0.699(95%CI:0.660 ～ 0.737)， 0.747(95%CI:0.709 ～ 0.785), with a statistically significant difference (Z=3.029, 3.690, 2.789；P=0.003, 0.000, 0.015). Conclusion　The serum levels of sPD-1 and sPD-L1 in patients with ITP increased, which would be risk factors affecting the therapeutic efficacy of ITP. The combined model of serum sPD-1, sPD-L1 and MPV has higher diagnostic value for the therapeutic efficacy of ITP.

参考文献/References:

[1] COOPER N, GHANIMA W. Immune thrombocytopenia[ J]. New England Journal of Medicine, 2019, 381(10): 945-955.
[2] 宋丽, 杜宁超, 李富荣． 儿童慢性ITP 外周血CD3+T 细胞活性氧的检测及临床意义[J]．现代检验医学杂志, 2020, 35(6): 144-148． SONG Li, DU Ningchao, LI Furong. Detection and clinical significance of CD3+T cell reactive oxygen species in peripheral blood of children with chronic ITP[J]. Journal of Modern Laboratory Medicine, 2020, 35(6): 144-148.
[3] DESOUZA S, ANGELINI D. Updated guidelines for immune thrombocytopenic purpura: Expanded management options[J]. Cleveland Clinic Journal of Medicine, 2021, 88(12): 664-668.
[4] BUSSEL J, COOPER N, BOCCIA R, et al. Immune thrombocytopenia[J]. Expert Review of Hematology, 2021, 14(11): 1013-1025.
[5] ?WIDERSKA J, KOZ?OWSKI M, NOWAK K, et al. Clinical relevance of soluble forms of immune checkpoint molecules sPD-1, sPD-L1, and sCTLA-4 in the diagnosis and prognosis of ovarian cancer[J]. Diagnostics （Basel, Switzerland）, 2022, 12(1): 189.
[6] ANDREWS L P, YANO H, VIGNALI D A A. Inhibitory receptors and ligands beyond PD-1, PDL1 and CTLA-4: breakthroughs or backups[J]. Nature Immunology, 2019, 20(11): 1425-1434.
[7] 中华医学会血液学分会止血与血栓学组. 成人原发免疫性血小板减少症诊断与治疗中国专家共识(2016 年版)[J]. 中华血液学杂志, 2016, 37(2): 89-93. Thrombosis and Hemostasis Group, Hematology Society, Chinese Medical Association. Consensus of Chinese experts on diagnosis and treatment of adult primary immune thrombocytopenia (version 2016) [J]. Chinese Journal of Hematology, 2016, 37(2): 89-93.
[8] BRADBURY C A, PELL J, HILL Q , et al . Mycophenolate mofetil for first-line treatment of immune thrombocytopenia[J]. New England Journal of Medicine, 2021, 385(10): 885-895.
[9] 王萍, 张佳佳．T 淋巴细胞亚群在原发免疫性血小板减少症外周血中的表达及临床意义[J]. 黑龙江医学, 2019, 44(9): 1022-1024. WANG Ping, ZHANG Jiajia. Expression of T lymphocyte subsets in peripheral blood of primary immune thrombocytopenia and its clinical significance [J]. Heilongjiang Medical Journal, 2019, 44(9): 1022-1024.
[10] DAMMEIJER F, VAN GULIJK M, MULDER E E, et al. The PD-1/PD-L1-checkpoint restrains T cell immunity in tumor-draining lymph nodes[J]. Cancer Cell, 2020, 38(5): 685-700, e8.
[11] HOSSEINZADEH R, FEIZISANI F, SHOMALI N, et al. PD-1/PD-L1 blockade:Prospectives for immunotherapy in cancer and autoimmunity[J]. IUBMB Life, 2021, 73(11): 1293-1306.
[12] ENNINGA E A L, HARRINGTON S M, CREEDON D J, et al. Immune checkpoint molecules soluble program death ligand 1 and galectin-9 are increased in pregnancy[J]. American Journal of Reproductive Immunology, 2018, 79(2): e12795.
[13] WU Die, LIU Ying, PANG Nannan, et al. PD-1/PD-L1 pathway activation restores the imbalance of Th1/Th2 and treg/Th17 cells subtypes in immune thrombocytopenic purpura patients[J]. Medicine(Baltimore), 2019, 98(43): e17608.
[14] BRUNET-RATNASINGHAM E, MOROU A, DUB? M, et al. Immune checkpoint expression on HIVspecific CD4+T cells and response to their blockade are dependent on lineage and function [J]. EBio Medicine, 2022, 84: 104254.
[15] LI Qinzhi, LIU Yang, WANG Xiujuan, et al. Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia[J]. Experimental Biology and Medicine (Maywood, N.J.), 2021, 246(15):1688-1697.
[16] YU Ling, ZHANG Liqin, JIANG Zhiyong, et al. Decreasing LncRNA PVT1 causes Treg/Th17 imbalance via NOTCH signaling in immune thrombocytopenia[J]. Hematology, 2021, 26(1): 734-740.
[17] STIMPSON M L, LAIT P J P, SCHEWITZ-BOWERS L P, et al. IL-10 and IL-17 expression by CD4+T cells is altered in corticosteroid refractory immune thrombocytopenia (ITP)[J]. Journal of Thrombosis and Haemostasis, 2020, 18(10): 2712-2720.
[18] HOU Yu , X I E J i e , WANG Shuwe n , e t a l . Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia[J]. Cellular & Molecular Immunology, 2022, 19(7): 764-776.
[19] LOEUILLARD E, YANG Jingchun, BUCKARMA E, et al. Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma[J]. Journal of Clinical Investigation, 2020, 130(10): 5380-5396.
[20] 刘五香, 袁相波, 孙红. 血小板参数动态检测及分析在ITP 患儿病情评估中的应用价值[J]. 河南外科学杂志, 2022, 28(4): 149-151. LIU Wuxiang, YUAN Xiangbo, SUN Hong. The application value of dynamic detection and analysis of platelet parameters in the evaluation of ITP patients[J]. Henan Journal of Surgery, 2022, 28(4): 149-151.
[21] 郝英婵, 程莉, 曾菊, 等．MPV, PDW, P-LCC 等参数联合检测在儿童免疫性血小板减少性紫癜中的诊断价值[J]. 国际检验医学杂志, 2022, 43(8): 1002-1005． HAO Yingchan, CHENG Li, ZENG Ju, et al. Diagnostic value of MPV, PDW and P-LCC and other parameters combined detection in children with immune thrombocytopenic purpura [J]. International Journal of Laboratory Medicine, 2022, 43(8): 1002-1005.

备注/Memo

备注/Memo:
基金项目：四川省科学技术厅基金项目[2019YJ0063]：血清可溶性程序性死亡受体1 及其配体在免疫性血小板减少性紫癜中的研究。
作者简介：田秋霞（1979-），女，硕士，检验技师，从事血液疾病诊断、检验方向研究，E-mail：tianqiuxia19@163.com。
更新日期/Last Update: 2023-07-15