Interleukin 17A as a good predictor of the severity of Mycoplasma pneumoniae pneumonia in children

Abstract

Early distinction between severe Mycoplasma pneumoniae pneumonia (MPP) and mild MPP is still difficult. The aim of this study was to analyze cytokines in bronchoalveolar lavage fluid (BALF) and explore predicting factors of severe MPP in children. Retrospective analysis was performed on 150 children with MPP or bronchial foreign body (FB) admitted in our hospital. The mRNA levels of IL17A were found significantly lower in severe MPP group comparing with mild MPP group or FB group. However, no significant difference was found in the levels of IL4, IL10 or interferon beta1 (IFNβ1) between the two groups. Receiver operator characteristic (ROC) curve analysis showed that IL17A can be used to distinguish severe MPP from mild MPP. These results were confirmed in a validation cohort including 40 MPP children from another hospital. IL17A levels were correlated with some clinical characters, such as refractoriness and pleural effusion. Lower IL17A levels were more likely to be found in refractory MPP children or in MPP children with pleural effusion. Moreover, the protein levels of IL17A in BALF were also found greatly decreased in children with severe MPP. Thus, decreased IL17A levels in BALF may be a valuable biomarker to identify severe MPP in children.

Figure 1

mRNA levels of different cytokines in BALF of children with MPP. (a) Relative expression levels of IL17A in control, mild MPP and severe MPP children. (b) Relative expression levels of IL4 in control, mild MPP and severe MPP children. (c) Relative expression levels of IL10 in control, mild MPP and severe MPP children. (d) Relative expression levels of IFNβ1 in control, mild MPP and severe MPP children. (e) Receiver operating characteristic (ROC) curve to evaluate the predicting value of IL17A in differentiating mild MPP from severe MPP. (f) ROC curve to evaluate the predicting value of IL4 in differentiating mild MPP from severe MPP. (g) ROC curve to evaluate the predicting value of IL10 in differentiating mild MPP from severe MPP. (h) ROC curve to evaluate the predicting value of IFNβ1 in differentiating mild MPP from severe MPP. The results of Benjamini-Hochberg p adjust are shown as: *p_adj < 0.05, **p_adj < 0.01, ***p_adj < 0.001.

Figure 2

mRNA levels of different molecules in BALF of MPP children grouped with different clinical indicators. mRNA levels of IL17A (a), IL4 (b), IL10 (c) and IFNβ1 (d) in general MPP and refractory MPP children. mRNA levels of IL17A (e), IL4 (f), IL10 (g) and IFNβ1 (h) in MPP children with pleural effusion and MPP children without pleural effusion. (i) mRNA levels of RORγt in BALF of mild MPP and severe MPP children. (j) mRNA levels of RORγt in BALF of general MPP and refractory MPP children. (k) mRNA levels of RORγt in BALF of MPP children with pleural effusion and MPP children without pleural effusion. (l) The correlation of the mRNA levels of RORγt and IL17A in BALF of MPP children. The results of Benjamini-Hochberg p adjust are shown as: *p_adj < 0.05, **p_adj < 0.01, ***p_adj < 0.001.

Figure 3

Protein levels of IL17A in BALF of MPP children. (a) Protein levels of IL17A in control, mild MPP and severe MPP groups. (b) ROC curve performed to evaluate the threshold of IL17A in differentiating mild MPP from severe MPP. Protein levels of IL17A reached area under the curve: 0.8720, p value: < 0.0001, cut off value: 1.366 pg/ml. It reached a sensitivity of 0.7692, a specificity of 0.8462, a positive predictive value of 0.8333 and a negative predictive value of 0.7857. (c) Protein levels of IL17A in control group, general MPP group and refractory MPP group. (d) Protein levels of IL17A in control group, MPP without pleural effusion group and MPP with pleural effusion group. The results of Benjamini-Hochberg p adjust are shown as: *p_adj < 0.05, **p_adj < 0.01, ***p_adj < 0.001.

Figure 4

mRNA levels of different cytokines and protein levels of IL17A in BALF of MPP children from Changchun Children’s Hospital. (a) mRNA levels of IL17A in BALF of mild MPP and severe MPP children. (b) mRNA levels of IL4 in BALF of mild MPP and severe MPP children. (c) mRNA levels of IL10 in BALF of mild MPP and severe MPP children. (d) mRNA levels of IFNβ1 in BALF of mild MPP and severe MPP children. (e) Protein levels of IL17A in mild MPP and severe MPP children. The results of Benjamini-Hochberg p adjust are shown as: *p_adj < 0.05, **p_adj < 0.01, ***p_adj < 0.001.