Specific antigens in malignancy-associated membranous nephropathy

Abstract

Membranous nephropathy (MN) is a glomerular disease mediated by autoimmune complex deposition, with approximately 30% of cases attributed to secondary causes. Among them, malignant tumors are a significant cause of secondary MN. Recent advancements in the identification of MN-specific antigens, such as THSD7A and NELL-1, suggest a potential association with malignant tumors, yet definitive proof of this relationship remains elusive. Therefore, this article aims to review the distribution of MN-specific antigens in patients with MN caused by malignant tumors and the possible role of these antigens in the pathogenesis of the disease.

Keywords: NELL-1; PLA2R; THSD7A; malignant tumor; membranous nephropathy.

Figure 1

The proposed pathogenesis of malignancy-associated membranous nephropathy. Different types of tumors secrete tumor-associated antigens such as THSD7A, NELL-1, and PLA2R. The antigen is ingested by an antigen-presenting cell (APC), cut into peptide segments, presented to the APC surface, interacts with helper T cells (Th cell), specifically recognizes B cells, promotes the differentiation of B cells into mature plasma cells, secretes antibodies related to THSD7A, NELL-1, and PLA2R, and forms an antigen–antibody immune complex with the tumor antigen, which circulates to the glomerulus and deposits on the basement membrane of the glomerulus, causing MN. PLA2R, phospholipase A2 receptor; THSD7A, thrombospondin domain-containing 7A; NELL-1, neural epidermal growth factor-like 1 protein. The illustration was created with BioRender.com.