A Novel Insight into the Role of PLA2R and THSD7A in Membranous Nephropathy

Figure 1

Schematic and epitope spreading of phospholipase A2 receptor (PLA2R) and of thrombospondin type 1 domain-containing 7A (THSD7A). The extracellular part of PLA2R contains an N-terminal cysteine-rich (CysR, or ricin B) domain, a single fibronectin type 2 (FnII) domain, and eight C-type lectin-like domains (CTLDs). The major epitopes are located in the CysR, CTLD1, and CTLD7 domains. THSD7A is a type 1 transmembrane protein with a large extracellular N-terminal region comprising 21 thrombospondin type 1 domains (TSDs) and a coiled coil domain in the extracellular. The predominant target of autoimmunity in two antigens existed in the N-terminal region. Epitope spreading begins with the outermost epitope of the target antigen, and then, other dominant immune epitopes within the molecule or on neighboring molecules are exposed as the disease progresses, which are accompanied by the increase of proteinuria and the decrease of remission.