Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndrome has gained recognition. The study by Colucci and colleagues provides preliminary evidence that production of deglycosylated IgM that is unable to regulate T-cell function in the presence or absence of corticosteroid may be responsible for a steroid-dependence course in SSNS. This study provides invaluable insights into the mechanistic roles of both T-cell and B-cell responses in the pathogenesis and clinical course of SSNS.