反复呼吸道感染儿童血清维生素A、维生素E水平与免疫球蛋白、T淋巴细胞亚群、NK细胞及骨密度的关系分析

摘要 目的：探讨反复呼吸道感染（RRTI）儿童血清维生素A、维生素E水平与免疫球蛋白（Ig）、T淋巴细胞亚群、NK细胞及骨密度的关系。方法：选择2018年2月至2020年12月我院儿科收治的107例RRTI患儿（感染组）和83例同期于我院体检的健康儿童（对照组）为研究对象,检测两组血清维生素A、维生素E水平、Ig水平,外周血T淋巴细胞亚群、NK细胞占比以及骨密度。分析维生素A、维生素E与Ig、T淋巴细胞亚群、NK细胞及骨密度的相关性。结果：感染组血清维生素A、维生素E、IgG、IgA、IgM及外周血CD3⁺T细胞百分比、CD4⁺T细胞百分比、CD3^-CD56⁺ NK细胞百分比、CD56brightNK细胞百分比、CD56dimNK细胞百分比、桡骨和胫骨骨密度均低于对照组（P＜0.05）,外周血CD8⁺T细胞百分比高于对照组（P＜0.05）。血清维生素A及维生素E水平与外周血CD8⁺T细胞百分比呈负相关（P＜0.05）,与IgG、IgA、IgM水平,外周血CD3⁺ T细胞百分比、CD4⁺T细胞百分比、CD3^-CD56⁺ NK细胞百分比、CD56brightNK细胞百分比、CD56dimNK细胞百分比、桡骨和胫骨骨密度呈正相关（P＜0.05）。结论：RRTI患儿血清维生素A、维生素E水平明显降低,且与免疫功能障碍和骨密度降低有关。     

传染性单核细胞增多症患儿NLR、CD4+/CD8+比值、ADA与EBV-DNA载量的相关性分析及对肝损害的影响

摘要 目的：探讨传染性单核细胞增多症（IM）患儿外周血中性粒细胞/淋巴细胞比值（NLR）、CD4⁺/CD8⁺比值、腺苷脱氨酶（ADA）与EB病毒（EBV）-脱氧核糖核酸（DNA）载量的相关性,分析其对IM患儿肝损害的影响。方法：选择2019年1月至2022年4月我院儿科收治的102例IM患儿（IM组）,另选择同期我科收治的95例EB病毒检测阴性的发热患儿（非IM组）和体检健康的73例健康儿童（对照组）。根据是否发生肝损害将IM患儿分为肝损害组（61例）和非肝损害组（41例）。比较外周血NLR、CD4⁺/CD8⁺比值、ADA与EBV-DNA载量,Pearson法分析NLR、CD4⁺/CD8⁺比值、ADA与EBV-DNA载量的相关性。多因素Logistic回归分析IM患儿发生肝损害的影响因素。结果：IM组ADA高于非IM组和对照组（P＜0.05）,且非IM组高于对照组（P＜0.05）,NLR、CD4⁺/CD8⁺比值低于非IM组和对照组（P＜0.05）,且非IM组低于对照组（P＜0.05）,IM组EBV-DNA载量高于非IM组（P＜0.05）。IM患儿ADA与EBV-DNA载量呈正相关（r=0.493,P＜0.05）,NLR、CD4⁺/CD8⁺比值与EBV-DNA载量呈负相关（r=-0.419、-472,P＜0.05）。肝损害组ADA、EBV-DNA载量高于非肝损害组（P＜0.05）,NLR、CD4⁺/CD8+⁺比值低于非肝损害组（P＜0.05）。肝脏肿大、高EBV-DNA载量、高ADA是IM患儿肝损害的危险因素（P＜0.05）,高NLR、高CD4⁺/ CD8⁺比值是保护因素（P＜0.05）。结论：IM患儿ADA增高,NLR、CD4⁺/CD8⁺比值降低,与EBV-DNA载量增加以及肝损害有关。     

外周血Treg细胞、T淋巴细胞及其亚群与早期宫颈癌的关系及对淋巴结转移的预测价值研究

摘要 目的：分析外周血Treg细胞、T淋巴细胞及其亚群与早期宫颈癌的关系及对淋巴结转移的预测价值。方法：选择我院自2017年1月至2020年12月接诊的60例接受子宫颈癌根治术及盆腔淋巴清扫术的早期宫颈癌患者作为观察组,另选同期的60例健康体检者作为对照组。比较两组外周血Treg细胞、T淋巴细胞及其亚群水平,使用受试者工作特征曲线（ROC）下面积（AUC）评价外周血Treg细胞、T淋巴细胞及其亚群对淋巴结转移的预测效能。结果：观察组外周血Treg细胞、CD8⁺T细胞水平高于对照组,CD3⁺T细胞、CD4⁺T细胞、CD4⁺/CD8⁺比值均低于对照组（P＜0.05）;观察组术后外周血Treg细胞、CD8⁺T细胞水平较术前降低,CD3⁺T细胞、CD4⁺T细胞、CD4⁺/CD8⁺比值均较术前升高（P＜0.05）;在60例早期宫颈癌患者中,发生淋巴结转移12例;淋巴结转移组术前外周血Treg细胞水平、CD8⁺T细胞高于非淋巴结转移组,CD3⁺T细胞、CD4⁺T细胞、CD4⁺/CD8⁺比值均低于非淋巴结转移组（P＜0.05）;经多因素Logistic回归分析,外周血Treg细胞、CD3⁺T细胞、CD4⁺/CD8⁺比值均是早期宫颈癌患者发生淋巴结转移的独立预测因素（P＜0.05）;经ROC曲线分析,外周血Treg细胞、CD3⁺T细胞联合CD4⁺/CD8⁺比值预测早期宫颈癌患者发生淋巴结转移的AUC为0.910。结论：外周血Treg细胞、T淋巴细胞及其亚群水平与早期宫颈癌的病情演变有关,其中外周血Treg细胞、CD3⁺T细胞联合CD4⁺/CD8⁺比值预测淋巴结转移的效能较好,值得进一步研究应用。     

脓毒症患者外周血T淋巴细胞PD-1表达变化及胸腺肽α-1的免疫调理作用研究

摘要 目的：探讨脓毒症患者外周血T淋巴细胞程序性细胞死亡受体1（PD-1）表达特点,分析胸腺肽?琢-1治疗对患者免疫功能的影响。方法：选择2018年3月至2020年6月我院重症医学科收治的140例脓毒症患者（脓毒症组）和同期于我院进行体检的95例健康志愿者（对照组）,根据急性生理与慢性健康评估Ⅱ（APACHE Ⅱ）、序贯器官衰竭评估（SOFA）评分结果将脓毒症患者分为APACHE Ⅱ 0~10分组（51例）、11~20分组（62例）和＞20分组（27例）;SOFA评分0~5分组（48例）、6~10分组（60例）和＞10分组（32例）。检测外周血CD4⁺T细胞上PD-1表达、CD8⁺T细胞上PD-1表达,比较组间差异性。Pearson秩相关性分析外周血CD4⁺T细胞上PD-1表达、CD8⁺T细胞上PD-1表达与APACHE Ⅱ、SOFA评分相关性。根据治疗方法将脓毒症患者分为A组（60例）和B组（80例）,A组给予常规综合治疗和乌司他丁治疗,B组在A组的基础上联合胸腺肽α-1治疗,比较两组治疗前后外周血T淋巴细胞（CD3⁺、CD4⁺、CD8⁺）、NK细胞（CD3-CD16⁺CD56⁺）差异。结果：脓毒症组外周血CD4⁺T细胞上PD-1表达、CD8⁺T细胞上PD-1表达高于对照组（P＜0.001）,外周血CD4⁺T细胞上PD-1表达、CD8⁺T细胞上PD-1表达随APACHE Ⅱ、SOFA评分的增加而增高,各组间差异显著（P＜0.05）。Pearson秩相关分析结果显示外周血CD4⁺T细胞上PD-1表达、CD8+T细胞上PD-1表达与APACHE Ⅱ评分、SOFA评分呈正相关（r=0.569、0.475;0.653、0.509,P均＜0.05）。B组治疗后CD3⁺、CD4⁺、CD3-CD16⁺CD56⁺高于A组（P＜0.05）,CD8⁺低于A组（P＜0.05）。结论：脓毒症患者外周血CD4⁺、CD8⁺T细胞上PD-1表达均增高,其表达与病情严重程度密切相关。给予胸腺肽α-1治疗可改善患者免疫功能。     

手足口病合并脑炎患儿外周血T淋巴细胞亚群、血清VCAM-1及CRP的表达水平及其检测价值分析

摘要 目的：探讨与分析手足口病（HFMD）合并脑炎患儿外周血T淋巴细胞亚群、血清VCAM-1及CRP的表达水平及其检测价值。方法：2017年4月到2020年10月选择在本院诊治的手足口病合并脑炎患儿42例作为合并组,同期选择手足口病不合并脑炎患儿68例作为对照组,检测两组外周血T淋巴细胞亚群、血清血管细胞粘附分子-1（VCAM-）及C-反应蛋白（CRP）表达水平,并判断检测价值与进行相关性分析。结果：合并组的CD4⁺、CD8⁺T淋巴细胞相对比例都明显少于对照组（P<0.05）。合并组的血清VCAM-1及CRP含量明显高于对照组（P<0.05）。在80例患儿中,Spearsman分析显示CD4⁺、CD8⁺T淋巴细胞相对比例和血清VCAM-1、CRP含量都与手足口病合并脑炎的发生存在相关性（P<0.05）。二分类Logistic回归分析显示CD4⁺、CD8⁺T淋巴细胞相对比例和血清VCAM-1、CRP含量都为导致手足口病合并脑炎发生的重要因素（P<0.05）。结论：手足口病合并脑炎患儿多伴随有外周血T淋巴细胞亚群异常与血清VCAM-1、CRP的高表达,CD4⁺、CD8⁺T淋巴细胞相对比例、血清VCAM-1、CRP含量都为导致手足口病合并脑炎发生的重要因素。     

HIV/AIDS患者抗病毒治疗前HIV-1耐药情况调查及外周血CD8+T细胞CD38表达水平研究

摘要 目的：分析人免疫缺陷病毒/艾滋病（HIV/AIDS）患者抗病毒治疗前HIV-1耐药以及影响因素,探讨HIV/AIDS患者外周血CD₈⁺T细胞CD₃₈表达（CD₈⁺CD₃₈⁺T淋巴细胞百分比）与CD₄⁺T淋巴细胞计数的相关性。方法：选择2016年3月至2019年12月我院接诊的442例HIV/AIDS患者（HIV/AIDS组）和163例同期于我院进行体检的健康志愿者（对照组）,HIV/AIDS组扩增pol基因,进行HIV-1基因耐药分析,检测CD₈⁺CD₃₈⁺T淋巴细胞百分比、CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数。分析HIV/AIDS患者HIV-1耐药的影响因素,分析CD₈⁺CD₃₈⁺T淋巴细胞百分比与CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数相关性。结果：HIV/AIDS组442例HIV/AIDS患者中376例获得HIV-1 pol基因序列,HIV-1耐药35例,耐药率9.31%（35/376）。单因素分析结果显示耐药组和非耐药组在年龄、文化程度、感染途径、HIV病毒载量方面差异有统计学意义（P＜0.05）。多因素Logistic回归分析结果显示同性性传播、注射吸毒、高HIV病毒载量是HIV/AIDS患者抗病毒治疗前HIV-1耐药的危险因素（P＜0.05）。HIV/AIDS组外周血CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数低于对照组（P＜0.05）,CD₈⁺CD₃₈⁺T淋巴细胞百分比高于对照组（P＜0.05）。CD₈⁺CD₃₈⁺T淋巴细胞百分比与CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数呈负相关（P＜0.05）。结论：抗病毒治疗前HIV/AIDS患者存在一定HIV-1耐药率,传播途径、HIV-1病毒载量与HIV-1耐药有关。CD₈⁺T细胞表面CD₃₈过表达与HIV/AIDS 患者CD₄⁺T T细胞的过度消耗有关。     

肺癌患者外周血T淋巴细胞分型与抗核抗体之间的关系研究

摘要 目的：研究肺癌患者外周血T淋巴细胞分型与抗核抗体之间的关系。方法：选择2019年1月到2021年6月在我院接受治疗的肺癌患者81例作为研究组,并选择同期健康志愿者81例作为对照组,检测并比较两组患者外周血CD4⁺、CD8⁺和CD4⁺/CD8⁺淋巴细胞比例,以及抗核抗体血清滴度。比较不同抗核抗体、年龄、性别、TNM分期、肿瘤分化程度以及病理类型肺癌患者外周血CD4⁺、CD8⁺和CD4⁺/CD8⁺淋巴细胞比例。结果：（1）肺癌患者外周血CD4⁺和CD4⁺/CD8⁺淋巴细胞比例显著低于对照组,而CD8⁺淋巴细胞比例显著高于对照组（P<0.05）;（2）III+IV肺癌患者外周血CD4⁺、和CD4⁺/CD8⁺淋巴细胞比例均显著低于I+II肺癌患者,而CD8⁺淋巴细胞比例均显著高于I+II肺癌患者（P<0.05）;（3）小细胞肺癌患者外周血CD4⁺、和CD4⁺/CD8⁺淋巴细胞比例均显著低于非小肺癌患者,而CD8⁺淋巴细胞比例均显著高于非小肺癌患者（P<0.05）;（4）肺癌患者抗核抗体血清滴度显著高于对照组（P<0.05）;（5）抗核抗体阳性患者CD4⁺和CD4⁺/CD8⁺淋巴细胞亚群比例均显著低于抗核抗体阴性患者,而CD8⁺淋巴细胞亚群比例显著高于抗核抗体阴性患者（P<0.05）。结论：肺癌患者外周血T淋巴细胞亚群表达异常,并且其表达水平可能与抗核抗体滴度有关。     

NLR、25-（OH）D3、IL-6、PCT与重症肺炎支原体肺炎患儿免疫功能和预后不良的关系研究

摘要 目的：探讨中性粒细胞与淋巴细胞比值（NLR）、25-羟维生素D3 [25-（OH）D3]、白细胞介素-6（IL-6）、降钙素原（PCT）与重症肺炎支原体肺炎（MMP）患儿免疫功能和预后不良的关系。方法：选取2019年2月至2021年12月我院收治的106例重症MMP患儿作为重症组,同期收治的101例轻症MMP患儿（轻症组）作为对照。检测外周血中性粒细胞计数、淋巴细胞计数、T淋巴细胞亚群以及血清25-（OH）D3、IL-6、PCT水平,计算NLR。分析NLR、25-（OH）D3、IL-6、PCT与T淋巴细胞亚群的相关性。重症MMP患儿治疗后随访半年,根据重症MMP患儿的预后情况分为预后良好组（75例）和预后不良组（31例）,多因素Logistic回归分析影响重症MMP患儿预后的因素。结果：重症组NLR、IL-6、PCT水平,CD8⁺高于轻症组（P＜0.05）,25-（OH）D3水平、CD3⁺、CD4⁺、CD4⁺/CD8⁺低于轻症组（P＜0.05）。NLR、IL-6、PCT水平与CD3⁺、CD4⁺、CD4⁺/CD8⁺呈负相关（P＜0.05）,与CD8⁺呈正相关（P＜0.05）;25-（OH）D3与CD3⁺、CD4⁺、CD4⁺/CD8⁺呈正相关（P＜0.05）,与CD8⁺呈负相关（P＜0.05）。多因素Logistic回归分析显示：肺大片实变影、NLR（较高）、IL-6（较高）、PCT（较高）是重症MPP患儿预后不良的危险因素（P＜0.05）,25-（OH）D3（较高）是保护因素（P＜0.05）。结论：重症MMP患儿NLR、IL-6、PCT水平升高,25-（OH）D3水平降低,且与细胞免疫功能低下以及预后不良有关,检测NLR、IL-6、PCT、25-（OH）D3有助于评估重症MMP患儿的预后。     

急性高容量血液稀释联合控制性低中心静脉压对脊柱后路手术患者炎症免疫调节及血液保护作用研究

摘要 目的：探讨急性高容量血液稀释（AHH）联合控制性低中心静脉压（CLCVP）对脊柱后路手术患者炎症、免疫调节、血液保护的作用。方法：选择2020年1月至2022年12月于南京鼓楼医院行脊柱后路手术的120例患者作为研究对象,根据随机数字表法分为对照组、AHH组、AHH+CLCVP组,每组各40例。对照组给予乳酸钠林格氏液血液稀释,AHH组给予AHH血液管理,AHH+ CLCVP组给予AHH联合CLCVP血液管理。比较三组围术期指标、血流动力学指标、炎症因子指标、免疫功能指标的变化情况。结果： AHH+CLCVP组术中出血量、悬浮红细胞输注量低于AHH组和对照组（P＜0.05）,AHH组术中出血量、悬浮红细胞输注量低于对照组（P＜0.05）。与T1时间点相比,三组心率（HR）于手术开始后60 min（T2）~术毕（T3）先升高后降低（P＜0.05）,平均动脉压（MAP）先降低后升高（P＜0.05）,对照组和AHH组中心静脉压（CVP）于T2~T3先升高后降低（P＜0.05）,AHH+CLCVP组T0~T3 CVP保持稳定水平（P＞0.05）。AHH+CLCVP组T2~T3 HR低于AHH组和对照组（P＜0.05）,MAP高于AHH组和对照组（P＜0.05）,CVP低于AHH组和对照组（P＜0.05）,AHH组T2~T3 HR低于对照组（P＜0.05）,MAP高于对照组（P＜0.05）。与T1时间相比,三组血清降钙素原（PCT）、C反应蛋白（CRP）、白细胞介素-6（IL-6）水平、外周血CD8⁺于T2~术后24 h（T4）先升高后降低（P＜0.05）,外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺于T2~T4先降低后升高（P＜0.05）。AHH+CLCVP组T2~T4血清PCT、CRP、IL-6水平、外周血CD8⁺低于AHH组和对照组（P＜0.05）,外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺高于AHH组和对照组（P＜0.05）,AHH组T2~T4血清PCT、CRP、IL-6水平、外周血CD8⁺低于对照组（P＜0.05）,外周血CD3⁺、CD4⁺、CD4⁺/CD8⁺高于对照组（P＜0.05）。结论：AHH联合CLCVP可稳定脊柱后路手术患者血流动力学,减少术中出血量和输血量,降低炎症反应,提高免疫功能。     

狼疮性肾炎患者血清NETs、TWEAK、外周血CD4+T/CD8+T比例与疾病活动度及肾脏预后的关系

摘要 目的：探讨狼疮性肾炎（LN）患者血清中性粒细胞胞外诱捕网（NETs）、肿瘤坏死因子样凋亡微弱诱导剂（TWEAK）、外周血分化簇（CD）4⁺T/CD8⁺T比例与疾病活动度及肾脏预后的关系。方法：选取2021年8月～2022年8月川北医学院附属医院肾内科收治的LN患者137例（LN组）,根据系统性红斑狼疮疾病活动指数（SLEDAI）-2000评分分为轻度活动组（52例）、中度活动组（45例）、重度活动组（40例）。随访1年,根据肾脏相关终点事件发生情况分为预后不良组（43例）和预后良好组（94例）,另选取同期76名体检健康志愿者（对照组）。采用酶联免疫吸附法检测血清NETs、TWEAK水平,流式细胞术检测外周血CD4⁺T/CD8⁺T比例。Spearman相关性分析LN患者血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T与SLEDAI-2000评分的相关性,多因素Logistic回归分析LN患者预后不良的因素,受试者工作特征曲线分析血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T对LN患者预后不良的预测价值。结果：与对照组比较,LN组血清NETs、TWEAK水平升高,外周血CD4⁺T/CD8⁺T降低（P＜0.05）。轻度活动组、中度活动组、重度活动组血清NETs、TWEAK依次升高,外周血CD4⁺T/CD8⁺T依次降低（P＜0.05）。LN患者SLEDAI-2000评分与血清NETs、TWEAK呈正相关,与外周血CD4⁺T/CD8⁺T呈负相关（P＜0.05）。慢性肾脏病分期4期、SLEDAI-2000评分升高、NETs升高、TWEAK升高为LN患者预后不良的独立危险因素,估算肾小球滤过率升高、CD4⁺T/CD8⁺T升高为独立保护因素（P＜0.05）。血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T联合预测LN患者预后不良的曲线下面积为0.943,大于血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T单独预测的0.790、0.788、0.799（P＜0.05）。结论：LN患者血清NETs、TWEAK水平升高,外周血CD4⁺T/CD8⁺T降低,与疾病活动度及肾脏预后不良密切相关,血清NETs、TWEAK联合外周血CD4⁺T/CD8⁺T预测LN患者肾脏预后的价值较高。     

The immunopathogenesis of retroviral diseases: No immunophenotypic alterations in T,B, and NK cell subsets in SIVmac239-challenged rhesus macaques protected by SIVΔnef vaccination

Abstract: Immunophenotype analysis was used to characterize circulating lymphocyte subset levels in both rhesus monkeys that were chronically infected with SIV_mac239 and in those that had resisted SIV_mac239 infection as a result of prior vaccination with an attenuated SIV strain. Alterations in T, NK, and B cell subsets were compared with those previously identified in humans chronically infected with HIV [8–11, 14, 22]. The well-known decrease in CD4⁺ cell levels was observed in the SIV_mac239-infected animals. However, these animals had relatively little activation of circulating CD8⁺ T cells as compared with uninfected monkeys. This contrasts with chronically HIV-infected humans who have substantial activation of circulating CD8⁺ cells as evidenced by elevated HLA-DR and CD38 antigen expression on CD8⁺ cells as well as substantially increased percentages and numbers of total CD8⁺ cells. NK cells of the SIV_mac239-infected animals, on the other hand, demonstrated the same changes recently described in HIV-infected humans, i.e., a decrease in circulating percentages and a decreased amount of FcRIII (CD 16). B cell percentages were markedly increased in the SIV_mac239-infected animals, a finding also noted in some children with HIV infection but not in HIV-infected adults. SIVΔnef-vaccinated/SIV_mac239-challenged animals showed none of the immune alterations found in the SIV_mac239-infected monkeys, providing further confirmation of lack of SIV disease in these vaccinated animals.     

血清IL-6、IL-8、IgM抗体及T细胞亚群水平对新生儿先天性梅毒的诊断价值

目的:探讨血清白介素-6(IL-6)、白介素-8(IL-8)、IgM抗体及T细胞亚群对先天性梅毒新生儿的诊断价值。方法:选择2015年5月至2017年5月在我院进行临床治疗的先天性梅毒新生儿81例为观察组,另选同期来我院进行健康体检81例新生儿为对照组。比较两组患者血清IL-6、IL-8、T细胞亚群中CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)细胞及IgM抗体的阳性率。结果:治疗后,观察组血清IL-6、IL-8水平均明显高于对照组(P0.05),T细胞亚群中CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)明显低于对照组,而CD~(8+)T细胞比例高于对照组(P0.05)。19S-IgM-TP ELISA法检测出IgM的阳性率92.59%,明显高于TRUST法(74.07%)及TP-ELSA法(70.37%)(P0.05)。ROC曲线中,血清IL-8特异度为88.34%明显高于血清IL-6特异度81.48%、IgM抗体特异度60.13%、T细胞亚群特异度65.34%;IgM抗体的曲线面积88.91 cm~2明显大于IL-6的曲线面积45.09 cm~2、IL-8的曲线面积76.19 cm~2、T细胞亚群的曲线面积77.35 cm~2;T细胞亚群准备性67.89%明显高于IL-6准确性60.39%、IL-8准确性51.09%、IgM抗体准确性50.12;IgM抗体的灵敏度60.13%高于IL-6灵敏度59.19%、IL-8灵敏度42.35%、T细胞亚群灵敏度59.37%。具有比较意义(P0.05)。结论:血清IL-6、IL-8水平、T细胞亚群中CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)及IgM抗体阳性率是诊断先天性梅毒新生儿的重要指标。     

T淋巴细胞亚群、血红蛋白及血小板在类风湿关节炎患者中的表达及临床意义分析

摘要 目的：探讨T淋巴细胞亚群、血红蛋白及血小板在类风湿关节炎患者中的表达及临床意义。方法：选取我院2020年1月到2023年1月收治的100例类风湿关节炎患者作为研究对象,依照患者病情活动性进行分组,将活动期类风湿关节炎的35例患者分为活动期组,将65例缓解期类风湿关节炎患者分为缓解期组,另选取同期体检的50名健康志愿者作为对照组,对比三组患者CD3⁺、CD4⁺、CD8⁺以及CD4⁺/CD8⁺比值,并对比三组受检者血红蛋白及血小板表达水平。应用Spearman相关分析分析T淋巴细胞亚群、血红蛋白及血小板与类风湿关节炎活动程度的相关性,并应用logistic回归分析分析T淋巴细胞亚群、血红蛋白及血小板对类风湿关节炎活动期的独立预测价值。结果：三组受检者T淋巴细胞亚群表达水平对比有差异,且活动期组CD3⁺、CD4⁺、CD4⁺/CD8⁺水平较缓解期组和对照组低,CD8⁺水平较高（P＜0.05）;三组受检者血红蛋白及血小板表达水平对比差异显著,且活动期组血红蛋白水平较缓解期组和对照组低,血小板水平较高（P＜0.05）;Spearman相关分析结果显示：CD3⁺、CD4⁺、CD4⁺/CD8⁺、血红蛋白与类风湿关节炎病情活动程度呈负相关,CD8⁺、血小板与类风湿关节炎病情活动程度呈正相关（P＜0.05）;logistic回归分析结果表明：CD4⁺/CD8⁺升高、血红蛋白升高及血小板降低为类风湿关节炎活动期的独立影响因素（P＜0.05）。结论：类风湿关节炎患者在疾病活动期T淋巴细胞亚群相关细胞比例、血红蛋白及血小板表达水平会出现明显变化,且与其活动程度具有明显相关性。以CD4⁺/CD8⁺升高、血红蛋白升高及血小板降低情况可独立判定类风湿关节炎活动期,因此临床上对于上述指标升高的类风湿关节炎患者需及时改善治疗措施,改善患者预后水平。     

Activated lymphocytes during acute Epstein-Barr virus infection

Activated lymphocytes, as identified by HLA-DR expression, associated with acute Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) were shown to be a heterogeneous population containing significantly elevated cytotoxic/suppressor (CD8) T cells, natural killer (CD16) cells and helper (CD4) T cells. CD8 T cells were the primary activated population representing 24.5% of the total lymphocyte population. The activated CD4 T cells and natural killer cells accounted for 6.7% and 3.5% of the total lymphocyte population, respectively. Analysis of serum soluble interleukin 2 receptors (IL-2R) demonstrated significantly (p less than 0.001) elevated levels in the serum of acute IM patients compared with normal controls. Elevated levels of serum IL-2R were correlated (r = 0.67) with increased percentages of Leu 2a+/HLA-DR+T cells (i.e., activated CD8 T cells). Patients with X-linked lymphoproliferative syndrome and virus-associated hemophagocytic syndrome, two syndromes associated with severe acute EBV infections, demonstrated the most dramatic increase in serum IL-2R levels. These data demonstrate that EBV is associated with intense immune stimulation and that during acute IM activated lymphocytes, other than the CD8 T cells, may contribute to the immune response to EBV.     

Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia

Purpose: During an ongoing immune response, cytokines produced by T helper types 1 (Th1) and 2 (Th2) together with T cytotoxic types 1 (Tc1) and 2 (Tc2) are critical to the effectiveness of that response. Dysregulated expansion of one or the other subset may contribute to the impaired function of the T-cell-mediated immune system in cancer patients. In the present study we have investigated whether such dysregulation might exist in children with acute lymphoblastic leukemia (ALL). Methods: We analyzed 61 blood samples from 45 children with B cell precursor ALL and 16 healthy children. Interleukin(IL)-2, IL-4, and interferon γ (IFNγ) production of their respective purified CD4⁺ and CD8⁺ T cells were assessed at the single-cell level by intracellular-cytokine-staining flow cytometry. Results: At the time of diagnosis, IL-2-producing cell populations in CD4⁺ and CD8⁺ T cells were reduced below the normal range in 31 of 44 (70.5%) and 23 of 38 (60.5%) cases respectively. Similarly, IFNγ-producing cell populations in CD4⁺ and CD8⁺ T cells decreased in 17 of 44 (38.6%) and 18 of 38 (47.4%) cases respectively. Conversely cell populations capable of IL-4 production in CD4⁺ and CD8⁺ T cell subsets were increased in 13 of 30 (43.3%) and 15 of 30 (50.0%) cases respectively. Therefore, the Th1-to-Th2 and Tc1-to-Tc2 ratios (1.6 ± 2.2 and 7.7 ± 6.7 respectively) were significantly lower in peripheral blood T cells of ALL patients (n = 30) than those (6.0 ± 2.9 and 20.1 ± 10.3 respectively) in 15 healthy controls (P < 0.0001). Although both CD45RA⁺/CD4⁺ and CD45RA⁺/CD8⁺ cells significantly increased in 43 ALL patients (P < 0.05), there existed no apparent correlation between CD45 isoform expression and cytokine (IL-2 and IFNγ) production. Interestingly, the ability to produce both IL-2 and IFNγ was recovered in 8 cases examined, after complete remission had been achieved. Conclusion: These observations suggest that, in both CD4⁺ and CD8⁺ T cells of ALL patients, there is a dysregulation in the functionality of Th1 (Tc1) and Th2 (Tc2) cells with a gross reduction of Th1 (Tc1) cell populations and an expansion in Th2 (Tc2). Received: 12 November 1999 / Accepted: 2 January 2000     

CD4+ and CD8+ T Cell Activation Are Associated with HIV DNA in Resting CD4+ T Cells

The association between the host immune environment and the size of the HIV reservoir during effective antiretroviral therapy is not clear. Progress has also been limited by the lack of a well-accepted assay for quantifying HIV during therapy. We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1) in 30 antiretroviral-treated HIV-infected adults. We found a consistent association between the frequency of CD4⁺ and CD8⁺ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. This study highlights the need to further examine this relationship and to better characterize the biology of markers commonly used in HIV studies. These results may also have implications for reactivation strategies.     

An imbalance of T cell subgroups exists in children with sepsis

The purpose of this study is to explore the role of different T cell subgroups in the pathogenesis of sepsis in children. Flow cytometry was used to detect the changes in the activation status and the number of T cell subgroups in the peripheral blood of children with sepsis; healthy children were selected as the control group. Compared with healthy children, the number of CD4+ T cells in the peripheral blood of children with sepsis did not change significantly (Z = 1.945, P = 0.052); though the ratio decreased and the median level dropped from 34.6% to 30.7% (Z = 2.257, P = 0.024). However, the number of CD8+ T cells in the blood of children with sepsis increased, and the median level also increased from 0.2 × 10⁹/L to 0.4 × 10⁹/L (Z = ?2.404, P = 0.016). In addition, CD3+CD8+HLA-DR + cell level significantly increased, and the median level increased from 4.2% to 24.3% (Z = ?5.370, P = 0.000). There was a large heterogeneity in the hospitalization time of sepsis in clinical patients. Compared to patients with a mean hospital stay of 6 days, patients with a median hospital stay of 13 days had a lower CD3+CD4+CD25 + cells percentage, while the percentage of CD3+CD8+HLA-DR+ was higher, resulting in a more apparent increase of CD3+ CD8+HLA-DR+/CD3+CD4+CD25+. Therefore, the failure of CD4+ T cell activation and proliferation, and the excessive activation and proliferation of CD8+ T cells play an important role in the pathogenesis of sepsis. The increase of CD3+CD8+HLA-DR+/CD3+CD4+CD25 + ratio was associated with the extended course of sepsis.     

High Expression of Tumor HLA-DR Predicts Better Prognosis and Response to Anti-PD-1 Therapy in Laryngeal Squamous Cell Carcinoma

BackgroundHLA-DR is expressed in epithelial and several types of tumor cells. However, the correlation between tumor-expressed HLA-DR (teHLA-DR) and patient outcome as well as its regulation on the tumor microenvironment (TME) of laryngeal squamous cell carcinoma (LSCC) are yet to be elucidated.MethodsHematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. teHLA-DR tumor cell, CD4⁺ and CD8⁺ tumor-infiltrating T lymphocytes (TITLs) were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method and tested by the log-rank test method. Expression of teHLA-DR⁺ tumor cells and infiltration of T lymphocytes and their corresponding subgroups were analyzed by flow cytometry using fresh LSCC tissue samples.ResultsOur research discovered elevated expressions of multiple MHC-II-related genes in tumor compared to the adjacent normal tissue samples of LSCC patients. We also found that patients in the teHLA-DR high-expression group (teHLA-DR^high) tend to have less tumor recurrence and better survival outcomes compared to those in the teHLA-DR^low group. Intriguingly, teHLA-DR⁺ tumor cells had significantly higher PD-L1 and PD-L2 expression and their TME showed increased infiltrated T lymphocytes (TITLs). Flow cytometry analysis and IHC staining indicated that CD4⁺ TITLs but not CD3⁺ total TITLs or CD8⁺ TITLs were significantly enriched in teHLA-DR⁺ tumors.ConclusionsteHLA-DR may be a predictive marker for favorable prognosis and response to anti-PD-1/PD-L1 therapy of LSCC, possibly due to the increased CD4⁺ TITLs in the TME.     

HIV-1 infection abrogates CD8+ T cell mitogen-activated protein kinase signaling responses

Mitogen-activated protein kinase (MAPK) signaling pathways are dynamic and sensitive regulators of T cell function and differentiation. Altered MAPK signaling has been associated with the inflammatory and autoimmune diseases lupus and arthritis and with some pathogenic viral infections. HIV-1 infection is characterized by chronic immune inflammation, aberrantly heightened CD8⁺ T cell activation levels, and altered T cell function. The relationship between MAPK pathway function, HIV-1-induced activation (CD38 and HLA-DR), and exhaustion (Tim-3) markers in circulating CD8⁺ T cells remains unknown. Phosphorylation of the MAPK effector proteins ERK and p38 was examined by “phosflow” flow cytometry in 79 recently HIV-1-infected, antiretroviral-treatment-naïve adults and 21 risk-matched HIV-1-negative controls. We identified a subset of CD8⁺ T cells refractory to phorbol 12-myristate 13-acetate plus ionomycin-induced ERK1/2 phosphorylation (referred to as p-ERK1/2-refractory cells) that was greatly expanded in HIV-1-infected adults. The CD8⁺ p-ERK1/2-refractory cells were highly activated (CD38⁺ HLA-DR⁺) but not exhausted (Tim-3 negative), tended to have low CD8 expression, and were enriched in intermediate and late transitional memory states of differentiation (CD45RA⁻ CD28⁻ CD27^+/−). Targeting MAPK pathways to restore ERK1/2 signaling may normalize immune inflammation levels and restore CD8⁺ T cell function during HIV-1 infection.