Altered B-Lymphocyte Homeostasis in Idiopathic Nephrotic Syndrome

Frontiers in Pediatrics

article

Chen Ling¹  Xiaorong Liu¹  Xiaolin Wang²  Zhi Chen¹  Jianfeng Fan¹  Qun Meng¹  Nan Zhou¹  Qiang Sun¹  Lin Hua⁴  Jingang Gui² 

[1] 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;Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University;Laboratory of Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University;School of Biomedical Engineering, Capital Medical University

关键词: idiopathic nephrotic syndrome;    B cells;    children;    transitional B cell;    flow cytometry;   

DOI  :  10.3389/fped.2019.00377

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY