Autoantibodies Targeting Proteasome Subunit Alpha Type 1 in Autoimmune Podocytopathies

Key Points Serum anti-proteasome subunit alpha type 1 (PSMA1) autoantibodies were specifically elevated in the active phase of idiopathic nephrotic syndrome, which may assist in disease diagnosis and monitoring. Serum anti-PSMA1 antibodies could cause damage to the glomerular filtration barrier, which may be a pathogenic antibody of idiopathic nephrotic syndrome. PSMA1 played an important role in the maintenance of podocyte morphology and function. Background The antibody against proteasome subunit alpha type 1 (PSMA1) is a podocyte autoantibody in children with idiopathic nephrotic syndrome identified in our previous study. The aim of this study was to explore the characteristics of idiopathic nephrotic syndrome in children and the mechanism underlying its involvement in the development of idiopathic nephrotic syndrome. Methods The levels of serum anti-PSMA1 autoantibodies in children were detected through protein microarray and compared among different disease groups. The recombinant PSMA1 protein was injected subcutaneously and intraperitoneally into mice to observe glomerular morphology and function. The PSMA1-knockdown and PSMA1-overexpressing cell lines were constructed from mouse podocytes, and their cytoskeleton and function were analyzed. Homozygous zebrafish with psma1 knockout were observed. Results The levels of serum anti-PSMA1 autoantibodies were higher in children with idiopathic nephrotic syndrome and varied with urinary protein. In mice immunized with PSMA1, the presence of serum anti-PSMA1 autoantibody caused albuminuria and damage to the glomerular filtration membrane. Deficiency of PSMA1 impaired the podocyte cytoskeleton and physiological function. Complete deletion of psma1 caused edema, abnormal glomerular morphology, and effacement of foot processes in zebrafish. Conclusions PSMA1 played an important role in the maintenance of podocyte morphology and function.