Potential and pitfalls of measuring circulating anti-nephrin autoantibodies in glomerular diseases

Recent studies have identified autoantibodies targeting the podocyte protein nephrin in patients with primary podocytopathies such as minimal change disease, primary focal segmental glomerulosclerosis (FSGS), post-transplant recurrent FSGS and childhood idiopathic nephrotic syndrome. These antibodies bind nephrin and directly influence nephrin downstream signaling, with immense effect on the podocytes' cellular structure and function, substantially changing our understanding of antibody-mediated podocytopathies and disease classification. Their presence correlates with disease activity and holds great potential as a novel biomarker of anti-nephrin-associated podocytopathy. However, the detection of these potentially low-titre autoantibodies has proven challenging. In this review, we highlight and explain distinct detection methodologies with their advantages and disadvantages and discuss the potential of anti-nephrin autoantibodies as a novel biomarker in nephrotic syndrome for diagnosis, prognostication and therapeutic guidance in patients with nephrotic syndrome.