Evaluation of T-Cell receptor diversity in pediatric patients with minimal change nephrotic syndrome

To further elucidate the clinical relevance of T-cell abnormalities in minimal change nephrotic syndrome (MCNS), and to predict the consequences of MCNS, we studied T-cell receptor (TCR) diversity by analyzing CDR3 size distribution and the frequency of Vβ repertoire usage.

Participants comprised 36 pediatric patients with MCNS. 18 were frequent relapsers (FRs) and/or steroid-dependent (SD) and 18 were non-frequent relapsers (NFRs). Serial changes in TCR Vβ repertoires were analyzed for these two groups of patients. Frequencies of Vβ repertoire usage were determined by flow cytometry, and TCR CDR3 length distribution was analyzed by GeneScan.

In NFRs, abnormalities in the distribution of Vβ repertoires were few in both CD4+ and CD8+ T cells. In FRs/ SD patients, patterns were normal in CD4+ T cells, while selected Vβ repertoires were significantly increased in CD8+ T cells in some patients. Furthermore, TCR diversity was significantly reduced in CD8+ T cells in FRs/SD patients, as shown by marked skewing of CDR3 size distributions. Of note was the finding that some FRs/SD patients showed improvements in the initially abnormal TCR diversity with improvement in clinical symptoms, eventually becoming NFRs.

Analysis of TCR diversity may delineate the subgroup of FRs/SD patients and provide a rationale for early intervention with immunosuppressive therapy for these patients.