Genetic determinants of the development and course of membranous nephropathy

Abstract

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults and is classified as either primary (idiopatic) or secondary MN according to underlying etiology (the later result from some known disease such as systemic autoimmune diseases, infections, malignancies, drugs, etc). In recent years, phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as two major podocytic antigens involved in the pathogenesis of idiopatic MN (IMN). And the discovery of circulating antibodies specific for these target antigens has transformed the diagnostic workup and significally improved management of IMN. However why do such antibodies develop is not conclusively established. The role of underlying genetic factors is discussed. The review presents the results of recent studies, that have shown significant associations of specific genetic factors (particularly human leucocyte antigen class II and PLA2R1 genes) with IMN.

Advances of the experimental models of idiopathic membranous nephropathy (Review)

“…Whether purified anti-THSd7a igG4 can form immune deposits in this model will likely advance igG4 research Evidence of the significant correlation between specific genetic factors and iMn is accumulating (102,103). The human leukocyte antigen (Hla) gene has a strong gene correlation with the PLA2R gene and the interaction may be the basis of autoimmune injury (104). although no relevant study has described the polymorphism of the THSD7A gene, the combined application of THSD7A and PLA2R gene tests is helpful to further examine the correlation between the iMn pathogenesis and genes, providing an important value for the establishment of the genetic model of Mn.…”