Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents.

BACKGROUND

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 receptor 1 (PLAR1), thrombospondin type-1 domain-containing 7A (THSD7A), neutral endopeptidase (NEP), and cationic bovine serum albumin (BSA).

METHODS

Twelve children with MN were included in this study. Sera of all patients were analyzed for antibodies against PLAR1, 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 PLAR1, THSD7A, NEP, BSA, and all IgG subclasses.

RESULTS

Six patients were PLAR1-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 PLAR1-antibody-positive and 3 PLAR1-antibody-negative patients were available for additional analyses, confirming the diagnosis of PLAR1-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 PLAR1-associated MN and negative in the other biopsies. During follow-up (median 24 months), 4 children with PLAR1-associated MN went into remission, preceded by decline of PLAR1 antibodies. Five of the 6 PLAR1-antibody-negative children went into remission.

CONCLUSIONS

In children with MN, PLAR1-associated MN appears to be common, whereas MN associated with THSD7A, NEP or BSA was not encountered. PLAR1 antibody levels are closely associated with disease activity, whereas PLAR1-antibody-negative patients often have a good prognosis. However, the pathophysiology of MN in a considerable number of children remains unclear.