支气管肺发育不良早产儿生后早期外周血免疫图谱变化的研究

Peripheral blood immunogram changes during early life in premature infants with bronchopulmonary dysplasia

目的探讨支气管肺发育不良(bronchopulmonary dysplasia,BPD)早产儿生后早期外周血免疫图谱的变化。方法选择2022年4~6月中山大学附属第一医院和广东省第二人民医院新生儿科收治的出生胎龄≤32周早产儿进行横断面研究。根据2001年版BPD诊断标准将符合入组条件的患儿分为BPD组和非BPD组。生后28 d以上且校正胎龄36周以内时留取1 ml外周静脉血,采用流式细胞术检测,根据细胞表面蛋白将外周血免疫细胞分为10大群,统计各细胞群占比,比较两组间有无差异。结果共纳入14例患儿,BPD组9例,非BPD组5例。BPD组适应性免疫细胞群CD4^(+)幼稚T细胞[7.9%(1.2%,10.0%)比24.8%(15.8%,29.7%)]、浆母细胞[0.01%(0.00%,0.07%)比0.14%(0.04%,0.18%)]、先天性免疫细胞群中性粒细胞[0.66%(0.52%,1.58%)比3.94%(2.29%,6.02%)]、CD127^(+)多形核髓系抑制细胞(polymorphonuclear myeloid-derived suppressor cells,PMN-MDSCs)[13.4%(4.3%,59.8%)比74.8%(58.2%,83.3%)]、CD127^(+)单核细胞髓系抑制细胞[3.6%(3.1%,5.5%)比22.0%(8.3%,22.5%)]占比均低于非BPD组,差异有统计学意义(P<0.05)。PMN-MDSCs降低联合CD127^(+)PMN-MDSCs降低对BPD有较高的诊断价值,AUC=0.978(95%CI 0.910~1.000,P=0.004),灵敏度100%,特异度88.9%。结论早产儿生后早期中性粒细胞、CD127^(+)PMN-MDSCs等免疫细胞减少可能是导致炎症反应持续的原因之一,此种免疫细胞图谱的改变提示炎症反应在BPD发病过程中发挥作用。

Objective To study the peripheral blood immunogram changes during early life in premature infants with bronchopulmonary dysplasia(BPD).Methods From April 2022 to June 2022,premature infants with gestational age≤32 weeks admitted to our hospitals were enrolled.The infants were assigned into BPD group and non-BPD group according to BPD diagnostic criteria 2001 edition.Peripheral blood(1 ml)was collected 28 d after birth and within 36 weeks of corrected gestational age and examined using 17-color flow cytometry.Peripheral blood immunograms were compared between the two groups.Results A total of 14 infants were enrolled,including 9 in BPD group and 5 in non-BPD group.BPD group showed significantly lower percentage of both adaptive immune cells and innate immune cells than non-BPD group,adaptive immune cells:CD4^(+)naive T cells[7.9%(1.2%,10.0%)vs.24.8%(15.8%,29.7%)],plasmablast cells[0.01%(0.00%,0.07%)vs.0.14%(0.04%,0.18%)];innate immune cells:neutrophils[0.66%(0.52%,1.58%)vs.3.94%(2.29%,6.02%)],CD127^(+)polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)[13.4%(4.3%,59.8%)vs.74.8%(58.2%,83.3%)]and CD127^(+)monocytic(M)-MDSCs[3.6%(3.1%,5.5%)vs.22.0%(8.3%,22.5%)](all P<0.05).Conclusions The decrease of neutrophils,CD127^(+)PMN-MDSCs and other immune cells during early life in premature infants may contribute to the sustained inflammatory responses and pathogenesis of BPD.