Exostosin 1/Exostosin 2-associated membranous nephropathy. & Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy.

The identification of the phospholipase A2 receptor (PLA2R) as the commonest (70%) target antigen in the adult form of primary MN modified drastically the management of affected patients. The implementation of the immunohistochemical detection in the nephropathological workout was rapid. These first steps motivated lively research with the identification of thrombospondin type 1 domain containing 7A (THSD7A) in further 5% of cases. Very recently, a third antigen of the adult MN, exostosin 1 and 2 (EXT1 and EXT2), was detected in a subset of MN associated with autoimmune disease, as described by an international study group around Sanjeev Sethi and Pierre Ronco¹. This month, the same group describes a fourth antigen, detected after application of mass spectrometry on microdissected glomerula from paraffin-embedded, native kidney biopsies with the diagnosis of PLA2R/THSD7A-double negative MN, as performed earlier¹. They identified neural epidermal growth factor-like 1 protein (NELL-1), an ubiquitary protein strongly expressed in neural tissue. Both new antigens are detectable in immunohistochemistry with commercially available antibodies. The latter one could even be subject of monitoring through measurement of serum titer levels². More studies are required to comprehend the prevalence and the pathophysiology of such cases.