Circulating plasmablasts in children with steroid-sensitive nephrotic syndrome

Background The therapeutic efficacy of B cell-depleting anti-CD20 treatment in both pediatric and adult steroid-sensitive nephrotic syndromes (SSNS) suggests that B cells play a pathogenic role in the disease. In adults with minimal change disease (MCD), only circulating plasmablasts are increased during the active phase of the disease, among B cell subsets. These cells have not been studied yet in children with SSNS. Methods We retrospectively quantified by flow cytometry analysis circulating plasmablasts in 107 pediatric patients with SSNS (51 at disease onset, 27 during relapse, and 29 in remission). Data were compared with an equal number of age- and sex-matched healthy donors (HD). Results Circulating plasmablast levels, expressed as percentage of total CD19(+) B cells or as percentage of total lymphocytes, were normal in all SSNS subgroups, compared to HD. Patients in remission had significantly fewer circulating plasmablasts compared to patients at disease onset. No significant correlation was observed between plasmablast levels and proteinuria or serum proteins, at onset. Treatment with prednisone and mycophenolate mofetil significantly reduced circulating levels of plasmablasts, unlike treatment with prednisone and calcineurin inhibitors. Conclusions The B cell phenotype of children with SSNS differs from that of adults with MCD. This may justify different therapeutic approaches.

Automated summary

This study found that circulating plasmablast levels in pediatric SSNS patients were normal in all subgroups, with significantly fewer plasmablasts in remission compared to disease onset. Despite no significant correlation between plasmablast levels and proteinuria or serum proteins at onset, treatment with prednisone and mycophenolate mofetil significantly reduced plasmablast levels. These findings suggest potential differences in therapeutic approaches between children with SSNS and adults with MCD.