Decreased Circulating Transitional B-Cell to Memory B-Cell Ratio Is a Risk Factor for Relapse in Children with Steroid-Sensitive Nephrotic Syndrome

Abstract

Introduction: A significant proportion of children with SSNS (steroid-sensitive nephrotic syndrome) experience recurrence. Reliable biomarkers to predict flare are currently lacking because the pathogenesis of SSNS remains obscure. Objective: Since B cells may be involved in the pathogenesis of SSNS, we aimed to identify perturbations of B-cell subsets that might predict SSNS relapse. Methods: We measured levels of circulating B-cell subsets in 69 SSNS children by flow cytometry, between 2018 and 2019. We divided them into a relapse group and a nonrelapse group according to whether a relapse occurred within 1 year of follow-up. We used Cox survival analysis to assess correlations between B-cell subsets and relapse. In addition, recurrence-free survival curves were calculated using the Kaplan-Meier method. Results: The proportion of transitional B cells was significantly lower in the relapse group (5.3 ± 5.1% vs. 8.7 ± 4.3% in nonrelapse group, p = 0.007), while the proportion of memory B cells was significantly higher (8.4 ± 3.0% vs. 5.8 ± 3.3% in nonrelapse, p = 0.002). There was a significant decrease in the transitional B-cell to memory B-cell ratio (T/M) in the relapse group (p < 0.001). Univariate analysis revealed that transitional B cells, memory B cells, and the T/M ratio were significantly correlated with relapse in SSNS patients (p < 0.05). Multivariate analysis revealed that only T/M ratio (hazard ratio 0.278, 95% confidence interval 0.085–0.908, p = 0.034) was an independent risk factor for recurrence-free survival in SSNS patients. A cutoff value for the T/M ratio of 1.16 resulted in a sensitivity of 90% and specificity of 80% (area under the curve 0.909; p < 0.001). Kaplan-Meier curves of cumulative relapse-free survival, stratified by this cutoff value, were constructed, which showed that the cumulative relapse-free rates for cutoff values of >1.16 (n = 38) and ≤1.16 (n = 31) were 76.3 and 29.0%, respectively (χ² = 18.416, p < 0.001). Conclusions: Decreased transitional B/memory B ratio is associated with SSNS recurrence in the reported cohort. Thus, it may prove to be a useful marker to predict SSNS relapse in children.