Nephrotic syndrome (NS) is the most common glomerular disorder of childhood and a leading cause of pediatric renal failure; however the etiology of NS remains largely unknown. Recent reports demonstrating that an anti-CD20 antibody can induce remission of NS strongly suggest a potentially novel role for B cells in NS pathogenesis. In this report, the authors investigated B cell cytokine profiles following in vitro stimulation in a monozygotic twin pair discordant for NS. The results revealed that clear differences in the cytokine profiles of B cells exist between the patient and the unaffected twin. This is the first report of altered B lymphocyte responses among a monozygotic twin pair that is discordant for NS. Future studies are needed to identify cytokine differences that track with NS relapse and/or NS response to therapy.