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Front Pediatr. 2019 Oct 9;7:377. doi: 10.3389/fped.2019.00377. eCollection 2019.

Altered B-Lymphocyte Homeostasis in Idiopathic Nephrotic Syndrome.

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Beijing Key Laboratory of Pediatric Chronic Kidney Disease and Blood Purification, Department of Nephrology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Laboratory of Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
School of Biomedical Engineering, Capital Medical University, Beijing, China.


Background: B-cell-deleted therapy has been successfully used for children with idiopathic nephrotic syndrome (INS), suggesting that B cells may be involved in the pathogenesis of INS. B cells are a heterogenous population comprised of subpopulations distinguished by their phenotypes. However, few studies have focused on the alteration of B-cell homeostasis in INS. Methods: We measured the levels of B-cell subsets in the blood of 87 INS children via flow cytometry, prior to treatment with steroids. INS patients were divided into steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) groups based on their sensitivities to steroids after a one-month follow-up. Subsequently, we compared these INS patients with age- and sex-matched patients with relapse (n = 35) and remissions (n = 32), as well as healthy controls (n = 75). Results: We found that 65 SSNS patients exhibited an altered peripheral-blood B-cell-subset distribution, with increased levels of total, transitional, memory, IgM (immunoglobulin M) memory and switched-memory B cells compared to 22 SRNS patients. The proportion of total B cells was significantly higher in the SSNS group (22.1 ± 6.7% L, p < 0.001) than in the SRNS, remission, and control groups. In contrast, the levels of B-cell subsets in SRNS patients were generally the same as those in remission patients and healthy controls. Patients in relapse presented elevated memory B cells compared to those in other groups. The area under the ROC (receiver operating characteristic) curve of transition B cells at initial onset for the prediction of SSNS was 0.907 (95% confidence interval, 0.835-0.979). The analysis rendered an optimal cut-off value of 2.05 (% Lymphocyte) corresponding to 79.1% sensitivity and 90.9% specificity. Conclusions: We observed and verified that B-cell subsets are significantly altered in children with SSNS. We propose that elevated transitional B cells may be a promising marker for predicting successful immunosuppressive therapy during the initial onset of INS. Further research is needed to determine the function of memory B cells in INS.


B cells; children; flow cytometry; idiopathic nephrotic syndrome; transitional B cell

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