Clinical and immunological characterization of the index patient. (A) First renal biopsy was performed at the age of 15 months. Granular deposition of IgG along the periphery of the capillary loops (left) as seen in membranous nephropathy (MGN) was confirmed by transmission electron microscopy (TEM) (right), which showed electron dense deposits between basement membrane and podocytes (P), as well as deposits partially in resolution and incorporated by basement membrane material (arrows), consistent with MGN stage I to III (CL, capillary loop). (B) Histopathological analysis of a lymph node biopsy revealed unspecific, reactive follicular hyperplasia (arrow) but not the characteristic lymph node changes of autoimmune lymphoproliferative syndrome (ALPS) associated with CD95/FAS mutations (ALPS type 0/1a). The left and middle panels show hematoxylin and eosin stains, and the right panel shows anti-CD20 staining. (C) Representative FACS plots illustrating the aberrant B-cell phenotype including B-cell lymphopenia, decreased IgM- and IgG memory B cells, and increased numbers of CD21^low B cells. (D) Longitudinal analysis illustrates progressive decrease of CD19⁺ B cells and (E-G) persistence of the aberrant distribution of B-cell subsets. *First episode of nephrotic syndrome. #Treatment with anti-CD20. The dotted lines indicate the age-related 25th and 75th percentiles of the corresponding cells.²³