Thrombospondin domain-containing 7A (Thsd7a) is a large transmembrane glycoprotein expressed by podocytes. Its exact function remains speculative, but some features suggest a role in adhesion. In the context of membranous nephropathy (MN), an autoimmune kidney disease, Thsd7a has emerged as a significant autoantigen [2].

In MN, about 3-5% of primary cases are associated with anti-Thsd7a antibodies [1]. The presence of these autoantibodies is used for MN diagnosis, and their levels correlate with disease severity, serving as biomarker for monitoring disease progression and treatment response [1]. A recent study developed a mouse model of Thsd7a-associated MN using a commercially available antibody. This model showed that Thsd7a-associated MN involves both complement-mediated and autonomous podocyte injury. Complement depletion only partially attenuated proteinuria and glomerular injury, indicating that there are also complement-independent pathomechanisms. In vitro, anti-Thsd7a antibody exposure caused podocytopathic changes in primary podocytes [3].

In conclusion, Thsd7a, as an autoantigen expressed by podocytes, plays a crucial role in the pathogenesis of membranous nephropathy. The Thsd7a-associated MN mouse model has provided valuable insights into the complex mechanisms of podocyte injury in this disease, which may contribute to the development of novel treatments [3].

References:

1. Gu, Yan, Xu, Hui, Tang, Damu. 2021. Mechanisms of Primary Membranous Nephropathy. In Biomolecules, 11, . doi:10.3390/biom11040513. https://pubmed.ncbi.nlm.nih.gov/33808418/

2. Beck, Laurence H. 2017. PLA2R and THSD7A: Disparate Paths to the Same Disease? In Journal of the American Society of Nephrology : JASN, 28, 2579-2589. doi:10.1681/ASN.2017020178. https://pubmed.ncbi.nlm.nih.gov/28674044/

3. Liu, Jing, Malhotra, Deepak, Ge, Yan, Dworkin, Lance, Gong, Rujun. 2024. THSD7A-associated membranous nephropathy involves both complement-mediated and autonomous podocyte injury. In Frontiers in pharmacology, 15, 1430451. doi:10.3389/fphar.2024.1430451. https://pubmed.ncbi.nlm.nih.gov/39086386/