Membranous nephropathy-one morphologic pattern with different diseases.

Since the discovery of the phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) as endogenous antigens involved in the development of membranous nephropathy (MN) in over 80% of adult patients, substantial progress in the diagnosis, prognosis, and therapy of MN has been made. In most cases of patients with MN, it is now possible to specifically define the responsible pathogenic mechanisms of disease and make a diagnosis even without a renal biopsy. Moreover, the presence of antibodies in the blood and the detection of the antigens in renal biopsies allow the definite diagnosis without the morphologic uncertainties, which now still apply for only about 20% of all renal biopsies showing MN. The discovery that the expression of THSD7A in malignant tumors might serve as the site of primary antigen recognition for the immune system to start MN might lead to a better understanding of not only tumor-associated MN, which accounts for up to 10% of all patients with MN, but also of the pathomechanisms relevant for MN development in general.