Supplementary file 3_The composition of MDSC-subpopulations PMN-like, M-like, and e-like MDSC is associated with the severity of infectious mononucleosis in pediatric patients.pdf

BackgroundPrimary infection with the Epstein-Barr virus (EBV) in early childhood is often asymptomatic, whereas infection with EBV during adolescence or adulthood may lead to infectious mononucleosis (IM). Sometimes severe complications like hepatitis, spleen rupture, or myocarditis may appear during IM. Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of regulatory immune cells with immunosuppressive activities. However, not much is known about the role of MDSC in IM. We assessed a clinical translational prospective study to examine the role of MDSC during the early and late phases of IM in pediatric patients.
MethodWe performed a longitudinal analysis of PMN-like, M-like, and e-like MDSC frequencies in 37 pediatric patients during the early (V1 < 28 days after symptom onset (Tonset), V2 four to six weeks after Tonset) and late phases (V3 = six to 12 months after Tonset) of IM using flow cytometry-based analyses. In addition, we determined the correlation of frequencies of MDSC-like subpopulations with the complexity and severity of laboratory, clinical, and virological IM features.
ResultsWe detected comparable frequencies of total MDSC-like cells during the course of IM (V1 median: 22.87%, V2 median: 16.10%, and V3 median: 16.58% of CD33+ cells, respectively). However, we observed temporal dynamics of the MDSC-like subpopulations PMN-like, M-like, and e-like MDSC during the early and late phases of IM. The frequency of PMN-like MDSC decreased significantly from V1 to V2 (P < 0.001) and from V1 to V3 (P < 0.001). In contrast, the frequency of M-like MDSC decreased significantly from V1 to V2 (P = 0.015) and increased from V2 to V3 (P < 0.001). e-like MDSC frequencies increased significantly from V1 to V3 (P < 0.001). We observed an increase in the proportion of PMN-like MDSC with the IM-complexity and severity laboratory score and ferritin levels.
ConclusionOur data highlights the rationale for in-depth analyses of MDSC subpopulations in further studies on IM and contributes to obtaining a more differentiated picture of the ongoing changes in MDSC-like cell distribution and the relationship between frequencies of MDSC-like cells and the complexity and severity of laboratory, clinical, and virological IM features.

背景：儿童早期初次感染埃博斯坦-巴尔病毒（Epstein-Barr virus, EBV）通常无明显临床症状，而青春期或成年期感染该病毒则可能引发传染性单核细胞增多症（infectious mononucleosis, IM）。部分患者在IM病程中可能出现肝炎、脾破裂或心肌炎等严重并发症。髓系来源抑制细胞（myeloid-derived suppressor cells, MDSC）是一类具有免疫抑制活性的异质性调节性免疫细胞群体，但目前关于MDSC在IM中的作用尚不明晰。本研究开展一项临床转化前瞻性研究，旨在探讨MDSC在儿科患者IM早期与晚期阶段的作用。
方法：我们采用基于流式细胞术的分析方法，对37例儿科患者IM早期（V1：症状发作后<28天，记为Tonset；V2：症状发作后4~6周）及晚期（V3：症状发作后6~12个月）阶段的嗜中性粒细胞样（PMN-like）、单核细胞样（M-like）及内皮样（e-like）MDSC频率进行了纵向分析。此外，我们还分析了MDSC亚群频率与IM的实验室、临床及病毒学特征的复杂程度和严重程度之间的相关性。
结果：我们检测到，在IM的整个病程中，总MDSC样细胞的频率无显著差异（V1中位数：占CD33+细胞的22.87%；V2中位数：16.10%；V3中位数：16.58%）。但我们观察到，在IM的早晚期阶段，PMN样、M样及e样MDSC亚群存在明显的时序动态变化。PMN样MDSC的频率从V1至V2（P<0.001）及V1至V3（P<0.001）均显著降低。与之相反，M样MDSC的频率从V1至V2显著降低（P=0.015），但从V2至V3显著升高（P<0.001）。e样MDSC的频率从V1至V3显著升高（P<0.001）。我们还观察到，PMN样MDSC的比例与IM复杂程度及严重程度实验室评分、铁蛋白水平呈正相关。
结论：本研究数据表明，在后续IM相关研究中深入分析MDSC亚群具有重要理论价值，同时有助于更精准地刻画MDSC样细胞分布的动态变化，以及明确MDSC样细胞频率与IM的实验室、临床及病毒学特征的复杂程度和严重程度之间的内在关联。