The study of routine laboratory factors in children with mycoplasma pneumoniae pneumonia: serum uric acid may have anti‐inflammatory effect

Abstract Background High uric acid levels are a risk factor for cardiovascular disorders, and metabolic diseases; however, the role of serum uric acid (sUA) during the mycoplasma pneumoniae pneumonia (MPP) of children is poorly known. This study aimed to clarify the effects of sUA during the MPP of children. Methods This was a prospective cohort study of children with MPP from multi‐center inpatient departments from September 2019 to August 2020. Routine laboratory characteristics analyzed including ALT, AST, BUN, CREA, UA, LDH, CK‐MB, WBC, N%, PLT, and CRP. Subjects were divided into 3 groups: non‐MPP, mild MPP (MMPP), and severe MPP (SMPP). Results 949 subjects were enrolled, including 207 in non‐MPP, 565 in MMPP, and 177 in SMPP. The optimal cutoff value for sUA is 239 μmmol/L in receiver operating characteristic (ROC) curves analysis. Multivariate logistic regression showed that WBC and sUA had significance for protective effects between non‐MPP and SMPP, but CRP did not have significance between the two groups, N and PLT had significance for risk factors; WBC and sUA did not have significance for the protective effects between non‐MPP and MMPP, CRP had significance between the two groups, N and PLT had significance for the risk effects. Similarly, binary logistic regression showed UA, WBC, and CRP had significance for the protective effects between non‐MPP and MPP, but N and PLT had significance for the risk effects between the two groups. Conclusion Both multivariate and binary logistic regression demonstrated that sUA displayed a protective effect during the MPP of children, which meant sUA is anti‐inflammatory.


| INTRODUC TI ON
Uric acid (UA), the product of purine catabolism, is a damageassociated molecular pattern (DAMP) released from ischemic tissues and dying cells. 1,2 Primates include humans lost the uricase gene, and the direct consequence is that they have higher serum uric acid levels than other animals. 3 The mutation in the uricase gene that occurred during food scarcity and global cooling resulted in a survival advantage at that time. 4 Today, however, it is associated with hypertension, kidney disease, obesity, and diabetes. 5 Previous studies reported that UA can activate the NLRP3 (NLR family, pyrin domain containing 3) inflammasome. 6,7 Upon NLRP3 inflammasome activation, cells secrete increased amounts of pro-inflammatory cytokines, such as IL-1β and IL-18, 8 which subsequently accelerates the development of obesity, 9 and obesity-related conditions such as insulin resistance and cardiovascular complications, [9][10][11] type 2 diabetes, 12 and NAFLD. [13][14][15] NLRP3 is not only associated with sterile inflammation, but also associated with pathogenic infections. Mycoplasma pneumoniae is an atypical bacterial respiratory pathogen known to cause a range of airway inflammation and lung and extrapulmonary pathologies. Segoviady et al. reported that M. pneumoniae infection activates the NLRP3 inflammasome complex, leading to IL-1 secretion, inflammation, and innate immune cell activation in the lungs of infected C57BL/6 mice and in mouse bone marrow-derived macrophages (BMDMs). 16 In the process of evolution, humans have lost the capacity to synthesize uricase. 17  Therefore, we sought to investigate that sUA had a protective or risk effect during the M. pneumoniae infection of children. The result of the study showed that sUA during MPP of children had a protective effect on the body, which mechanism is needed to be further studied.

| Subjects
Research data were collected from multi-center inpatient de-

| Data collection
Laboratory data were retrospectively collected from all children who were included in the study. Characteristics analyzed liver func-

| Statistical Analysis
All data were analyzed using SPSS 20 (IBM), and p < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were used to analyze the optimal cutoff value of uric acid.
Normally distributed data were reported as mean ± standard deviation. One-way ANOVA was used to compare these data. Data with a skewed distribution were presented as median values (interquartile).  Table 1 showed that the main clinical features and laboratory values. The age was older in the SMMP samples than that in the non-MPP and MMPP, and the result was consistent with the previous report. 23 There was no significant difference in sex distribution among the 3 groups (p = 0.317). We also found that thermal spike, Fever >7 days, range of lung invasion, Pleural effusion, extrapulmonary complications, PLT, CRP, ALT, AST, LDH, BUN, CREA, and UA had significance; but WBC and CK-MB had no significance among the 3 groups (Table 1). The optimal cutoff value for uric acid is 239 μmmol/L in ROC analysis (AUC: 0.575, 95% CI: 0.511-0.638).

| RE SULTS
The results of binary regression analysis of the laboratory characteristics are shown in Table 2. On the basis of binary regression analysis,  Table 3. The Table 3 implied that WBC (p = 0.050, OR = 0.908, 95% CI (0.824-1.000)) and UA (p = 0.067, OR = 0.469, 95% CI (0.209-1.054)) did not have significance for protective effect between non-MPP and MMPP, but CRP (p = 0.007, OR = 0.970, 95% CI (0.948-0.991)) was a significant protective factor between the two groups, N (p = 0.035, OR = 1.030, 95% CI (1.002-1.058)) and PLT (p = 0.007, OR = 1.007, 95% CI (1.002-1.011)) were significant risk factors between the two groups; Table 3 also uncovered that WBC Range of lung invasion c 0 (0) 1 (0) 2 (0) ≤0.001 Extrapulmonary complications e 0 (0) 0 (0)  and EP (eosinophilic pneumonia). [26][27][28] But, according to binary regression analysis in the present study, we found that sUA, WBC, and CRP have significance for the protective effect between non-MPP and MPP groups, which meant they involved in the anti-inflammatory activity, but the OR value of CRP is proximal 1, so available protection is small. On the base of multiple logistic regression, sUA, WBC, and CRP did not have significance for protection between non-MPP and MMPP, which suggested that sUA and WBC had protection between the two groups, but the value of OR of WBC and CRP also was close to 1, so their protection is small; sUA and WBC had significance for the protection between non-MPP and SMPP, which it showed that sUA and WBC have antiinflammation between non-MPP and SMPP, and CRP was not significant between the two groups.
N and PLT were risk factors for MPP. Platelets have long been recognized as the major blood cells for activation of the coagulation system, and it can influence the different cell types including T-lymphocytes, neutrophils, mononuclear phagocytes, endothelial cells, and dendritic cells, activated platelets and could trigger inflammation. 29,30 In addition, neutrophils promote intravascular blood coagulation and thrombosis during infections and inflammatory responses. 31  In conclusion, we found that sUA has a protective effect during the MPP of children, which suggested it had the anti-inflammatory activity in the present study. The results suggested that urease loss may be one of the causes during human evolution. Further research needs to do determine whether NLRP3 and other signaling pathways are responsible for this anti-inflammation and whether physiological sUA is part of innate immune molecules.

ACK N OWLED G M ENT
None.

CO N FLI C T S O F I NTE R E S T
The authors declare that they have no conflicts of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the study are available from the corresponding author upon reasonable request.