The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome.

Abstract

BackgroundIn recent years, B-cell dysfunction has been found to play an important role in the pathogenesis of primary nephrotic syndrome (PNS). B cells play a pathogenic role by secreting antibodies against their target antigens after transforming into plasma cells. Therefore, this study aimed to screen the autoantibodies that cause PNS and explore their pathogenic mechanisms.MethodsWestern blotting and mass spectrometry were employed to screen and identify autoantibodies against podocytes in children with PNS. Both in vivo and in vitro experiments were used to study the pathogenic mechanism of PNS. The results were confirmed in a large multicenter clinical study in children.ResultsAnnexin A2 autoantibody was highly expressed in children with PNS with a pathological type of minimal change disease (MCD) or focal segmental glomerulosclerosis without genetic factors. The mouse model showed that anti-Annexin A2 antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A2 antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A2 at Tyr24 on podocytes by reducing its binding to PTP1B, which led to the cytoskeletal rearrangement and damage of podocytes, eventually causing proteinuria and PNS.ConclusionsAnnexin A2 autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.