Expression of PD-1 on T cells and its predictive value for steroid resistance in children with idiopathic nephrotic syndrome
摘要
Programmed cell death protein 1 (PD-1) plays a pivotal role in regulating T-cell responses. Its expression profile and clinical significance in pediatric idiopathic nephrotic syndrome (INS), particularly in steroid-resistant nephrotic syndrome (SRNS), remain unclear.
MethodsPD-1 expression on CD3⁺, CD4⁺, and CD8⁺T cells was quantified by flow cytometry in 65 treatment-naive children with idiopathic nephrotic syndrome (INS): steroid-sensitive (SSNS, n = 54), steroid-resistant (SRNS, n = 11), as well as in healthy controls (HC, n = 30). Group differences, clinical correlations and PD-1’s predictive value for SRNS were analyzed. Circulating T subsets, including CD3⁺PD-1⁺ T cells, CD4⁺PD-1⁺T cells, and CD8⁺PD-1⁺T were detected with multiparameter flow cytometry.
ResultsThe percentage of CD4⁺PD-1⁺ T cells was significantly higher in SRNS (10.77 ± 4.62%) compared to both SSNS (5.14 ± 1.99%, P = 0.000) and HC (6.36 ± 2.02%, P = 0.028). CD3⁺PD-1⁺ T cells were also elevated in SRNS (8.13 ± 3.12%) versus SSNS (4.67 ± 1.82%, P = 0.001). No significant difference was found in CD8⁺PD-1⁺ T cells. Multivariate logistic regression identified an elevated percentage of CD4⁺PD-1⁺ T cells as an independent risk factor for SRNS (OR = 2.236, P = 0.002). Receiver operating characteristic (ROC) analysis showed that CD4⁺PD-1⁺ T cell cutoff > 7.385% predicted SRNS with an area under the curve (AUC) of 0.891, sensitivity of 81.8%, and specificity of 87.0%.
ConclusionsOverexpression of PD-1, predominantly on CD4⁺ T cells, is associated with steroid resistance in pediatric INS. Elevated CD4⁺PD-1⁺ T cells may serve as a predictive biomarker for SRNS, offering a potential tool for early identification and a rationale for exploring PD-1 pathway modulation.
Graphical Abstract