Expression levels of myeloid-derived suppressor cells in children with biliary atresia and its clinical significance
Objective To investigate the expression levels of myeloid-derived suppressor cells(MDSCs)in peripheral blood and liver and their correlation with the prognosis of patients with biliary atre-sia(BA)after Kasai hepatic portoenterostomy(HPE).Methods A retrospective analysis was performed on 30 patients with BA(BA group)and 24 patients in control group at Department of Pediatric Surgery,Wuhan Union Hospital between January 2021 and September 2023 were retrospectively analyzed,including 30 patients who underwent Kasai surgery in BA group and 24 choledochal cysts patients in control group.Flow cytometry was used to detect the phenotype and proportion of MDSCs in the peripheral blood of two groups prior to surgery,as well as changes in arginase 1(ARG-1)activity and inducible nitric oxide syn-thase(iNOS)levels.Subsequently,the MDSCs expression levels in liver tissue and its correlation with the inflammation grade and fibrosis stage,as well as the relationship between MDSCs in peripheral blood and postoperative prognosis were evaluated.Independent sample t test was used to analyze the inter-group differences and Spearman test was used to analyze the correlation between variables.Results The MDSCs(HLA-DR-CD33+CD11b+)level in peripheral blood of BA group was significantly higher than that of control group[(34.85±1.35)%vs.(15.50±5.20)%,t=6.238,P<0.05],and the ARG-1 activity and iNOS levels produced by MDSCs in BA group were significantly higher than those of control group[(8 823.33±376.34)MFI vs.(5 633.33±500.83)MFI,t=-8.820,P<0.001;(9 623.33±851.25)MFI vs.(6 310.00±511.18)MFI,t=-5.780,P<0.01].The proportion of MDSCs in liver tissues of BA group was significantly higher than that of control group[(4.90±0.93)%vs.(0.60±0.06)%,t=8.029,P<0.01],among which the upregulated subset was mainly monocytic MDSCs(HLA-DR-CD33+CD11b+CD14+CD15-)[(38.73±1.65)%vs.(1.77±0.12)%,t=38.69,P<0.001].Moreover,the number of CD33+and CD11b+cells in liver tissue of BA patients were significantly associated with portal inflammation(r=0.517,0.567,P<0.05)and liver fibrosis grade(r=0.506,0.521,P<0.05).One year after HPE surgery,the levels of ARG-1 and iNOS of MDSCs in peripheral blood of patients with survival with native liver(SNL)were significantly higher than those of patients with non-SNL[(2 380.00±280.00)MFI vs.(1 626.67±166.23)MFI,t=-4.007,P<0.05;(4 066.67±435.58)MFI vs.(3 156.67±190.09)MFI,t=-3.316,P<0.05].Conclusion MDSCs levels were highly expressed in peripheral blood and liver tissue of BA patients,and SNL within postoperative 1 year was closely related to MDSCs immunosuppressive function.
Biliary atresiaMyeloid-derived suppressor cellsSurvival with native liverPathological features