Peripheral B-cell receptor immunoglobulin heavy chain repertoire as a potential biomarker for frequently relapsing nephrotic syndrome in children.

BACKGROUND

This study aimed to investigate the distribution characteristics of the peripheral blood B cell receptor (BCR) repertoire immunoglobulin heavy chain (IGH) in children with frequently relapsing nephrotic syndrome (FRNS), explore its dynamic changes before and after glucocorticoid therapy, and evaluate its potential value as a biomarker for predicting FRNS.

METHODS

35 newly diagnosed children with primary nephrotic syndrome (PNS) admitted to Xuzhou Medical University Affiliated Hospital from September 2024 to September 2025 were divided into the FRNS group (n = 20) and the NFRNS group (n = 15), and 15 healthy children were selected as the control group. High-throughput sequencing was used to analyze the usage patterns, CDR-H3 length, somatic hypermutation (SHM), and diversity index of IGH genes in all subjects.

RESULTS

Before glucocorticoid treatment, compared with the NFRNS group, the FRNS group showed significantly increased IGH gene usage bias, shorter CDR-H3 length, higher SHM, and decreased BCR repertoire diversity (all p < 0.05). These abnormalities persisted or showed further deviation in the FRNS group after treatment but returned to near-normal levels in the NFRNS group. Pretreatment factors such as a lower Shannon index, a shorter CDR-H3 length, and a higher rate of SHM were significantly associated with poorer clinical remission in FRNS patients after treatment (all p < 0.01).

CONCLUSION

Characteristics of the IGH repertoire in FRNS patients, especially the Shannon index, may serve as potential biomarkers for early risk stratification and personalized treatment of PNS in children.