01.04.2024 | Editorial Commentary
(T-) Regulation of Immunity in Membranous Nephropathy
verfasst von:
Georgie Mathew, Aditi Sinha
Erschienen in:
Indian Journal of Pediatrics
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Excerpt
Idiopathic membranous nephropathy (IMN), an important etiology of nephrotic syndrome in adults, is uncommon in childhood. Histologically, the entity is characterised by stiffening of the glomerular capillary walls due to formation of immune complexes, visible as ‘spikes and craters’ in the glomerular basement membrane on special stains, linear IgG deposits on immunofluorescence, and subepithelial deposits on electron microscopy. Our understanding of the pathophysiology of the condition has evolved considerably in the last two decades [
1]. The Heymann nephritis rat model of the 1970s adequately mimicked human MN, but the implicated antigen, namely megalin (or LRP2), is not expressed in human podocytes. In 2002, the rare entity of neonatal MN was ascribed to alloimmunization of pregnant women who are congenitally deficient in neural endopeptidase (a membrane-bound zinc metalloproteinase) following exposure to the paternally derived placental antigen: placental transfer of maternal antibodies to the fetus was followed by
in situ immune complex formation in the fetal/neonatal podocytes [
2]. The identification, in 2009, of phospholipase A2 receptor (PLA2R), a podocyte transmembrane glycoprotein, as the key antigen evoking an autoimmune response, heralded a radical transformation in the management of MN [
3]. Additional antigens were subsequently identified, including NEL-like protein 1 (NELL1), thrombospondin type 1 domain-containing 7A (THSD7A) and protocathedrin 7 (PCDH7) in adult-onset MN, sometimes associated with malignancy; semaphorin 3b (SEMA3B) in childhood-onset MN; and exostosin (EXT1, EXT2) and neural cell adhesion molecule 1 (NCAM1) in type V lupus nephritis. This led to the proposal of an antigen-based management algorithm that allows specific diagnosis and has implications for targeted treatment and outcomes [
4]. …