Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, but is less frequent in children. Antibodies against four antigens leading to MN have been described in children: phospholipase A(2) receptor 1 (PLA(2)R1), thrombospondin type-1 domain-containing 7A (THSD7A), neutral endopeptidase (NEP), and cationic bovine serum albumin (BSA). Twelve children with MN were included in this study. Sera of all patients were analyzed for antibodies against PLA(2)R1, THSD7A, NEP, and BSA. All sera were also analyzed using Western blot with human glomerular extracts (HGE) under non reducing conditions. In 5 cases renal biopsies were analyzed for PLA(2)R1, THSD7A, NEP, BSA, and all IgG subclasses. Six patients were PLA(2)R1-antibody-positive, whereas THSD7A, NEP, and BSA antibodies were not found in any of our 12 patients. All sera were analyzed by Western blot using human glomerular extracts; however, no further potential antigens were found. Five kidney biopsies from 2 PLA(2)R1-antibody-positive and 3 PLA(2)R1-antibody-negative patients were available for additional analyses, confirming the diagnosis of PLA(2)R1-associated MN in 2 cases, whereas none of the biopsies revealed enhanced staining for THSD7A, NEP or BSA. IgG2 and IgG4 stainings were positive in both patients with PLA(2)R1-associated MN and negative in the other biopsies. During follow-up (median 24 months), 4 children with PLA(2)R1-associated MN went into remission, preceded by decline of PLA(2)R1 antibodies. Five of the 6 PLA(2)R1-antibody-negative children went into remission. In children with MN, PLA(2)R1-associated MN appears to be common, whereas MN associated with THSD7A, NEP or BSA was not encountered. PLA(2)R1 antibody levels are closely associated with disease activity, whereas PLA(2)R1-antibody-negative patients often have a good prognosis. However, the pathophysiology of MN in a considerable number of children remains unclear.