Changes And Significance Of Type 2 Innate Lymphocytes And Their Related Factors In Bronchopulmonary Dysplasia

Objective:To investigate the changes and significance of Group 2 innate lymphoid cells(ILC2)and its related factors interleukin(IL)-33,IL-25,thymic stromal lymphopoietin(TSLP),IL-5 and IL13 in the occurrence and development of bronchopulmonary dysplasia(BPD)in premature infants,to provide theoretical basis for early prediction of BPD.Methods:Preterm infants with gestational age<32 weeks and length of stay≥14 days admitted to the Neonatal intensive care Unit of Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were selected as subjects.According to the diagnostic criteria for BPD,they were divided into BPD group(30 cases)and non-BPD group(46 cases).General data of the infants were collected on the day of admission.Peripheral venous blood was collected at 1,7 and 14 days after birth.Flow cytometry was used to detect the percentage of ILC2 count in lymphocytes.IL-33,IL-25,TSLP,IL-5 and IL-13 levels were detected by enzyme-linked immunosorbent assay(EILSA).With BPD or not as the dependent variable,general clinical data with great influence on the occurrence of BPD were controlled,and the cytokines with statistically significant differences between the two groups were used as independent variables for multivariate logistic regression analysis.Receiver operating characteristic(ROC)curves were drawn for statistically significant indicators,and the diagnostic efficacy of peripheral blood ILC2 and related cytokines for BPD was analyzed.Results:(1)A total of 76 infants were enrolled in the study,including 30(39%)BPD infants and 46(61)non-BPD infants.The gestational age and birth weight of BPD group were lower than those of non-BPD group[gestational age(29.1±1.0)weeks vs.(30.8±1.0)weeks;The birth weight was(1249±185)g vs(1664±168)g],the differences were statistically significant(all P<0.05),while there were no significant differences in gender,mode of birth,use of pulmonary surfactant,and prenatal steroid hormone use between the two groups(all P>0.05).(2)The percentage of ILC2 in peripheral blood of BPD group on days 7 and 14 after birth was higher than that of non-BPD group[7 d:(0.741±0.455)%vs.(0.641±0.414)%,and 14 d:(0.935±0.421)%vs.(0.819±0.478)%,all P<0.05].(3)The levels of IL-33,TSLP,and IL-5 in peripheral blood of BPD group were higher than those of non-BPD group on days 7 and 14 after birth[7 d:IL-33(3.89±0.32)pg/mL vs.(3.54±0.22)pg/mL,TSLP(11.09±1.15)pg/mL vs.(9.97±0.63)pg/mL,IL-5(4.50±0.58)pg/mL vs.(4.05±0.75)pg/mL;14 days:IL-33(4.66±0.31)pg/mL vs.(4.09±0.17)pg/mL,TSLP(14.99±1.39)pg/mL vs.(12.90±1.14)pg/mL,IL-5(5.48±0.43)pg/mL vs.(5.24±0.50)pg/mL];The differences were statistically significant(all P<0.05).(4)After adjusting for gestational age and birth weight,the occurrence of BPD was closely related to the increase of IL-33,TSLP and IL-5 in peripheral blood on days 7 and 14 after birth[7 d:IL-33(OR=56.513,95%CI:3.860-827.365,P=0.003),TSLP(OR=7.152,95%CI:3.860-827.365,P=0.003),95%CI:2.102-24.338,P=0.002),IL-5(OR=2.547,95%CI:1.220-5.315,P=0.013);14 d:IL-33(OR=69.471,95%CI:2.130-226.537,P=0.001),TSLP(OR=4.883,95%CI:2.263-10.536,P<0.001),IL-5(OR=3.109,P<0.001)95%CI:1.091-8.859,P=0.034)].The areas under the ROC curve of peripheral blood ILC2,IL-33,TSLP,and IL-5 for predicting BPD were 0.944,0.803,0.825,and 0.706 on day 7 and 0.961,0.949,0.850,and 0.708 on day 14,respectively.According to the results of ROC curve,the best cut-off values of ILC2,IL-33,TSLP and IL-5 were determined:The levels of ILC2,IL-33 and TSLP were 0.885%(sensitivity 86.7%,specificity 93.5%),4.275 pg/mL(sensitivity 90.0%,specificity 93.5%)and 15.050 pg/mL(sensitivity 66.7%,specificity 93.5%),respectively.Specificity 100%)and IL-55.435 pg/mL(sensitivity 63.3%,specificity 78.3%),the AUC of the four combined diagnoses was 0.968,which was higher in sensitivity and specificity than in the individual indexes.Conclusion:Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD.ILC2,IL-33,TSLP,and IL-5 may be used as biological indicators for early diagnosis of BPD.