Primary Membranous Nephropathy

The glomerular disease remains the leading cause of End-Stage Renal Disease (ESRD) in Asia and contributes significantly to ESRD in other parts of the world. Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of the cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). Most importantly, PMN increases by 13% annually as a predominant cause of glomerulopathy compared to others. This Research Topic focuses only on PMN.

PMN is an organ-specific autoimmune kidney disease caused by circulating autoantibodies that target the surface antigens on glomerular podocytes, such as PLA2R, THSD7A. Intriguingly, the corresponding autoantibodies switch to the IgG4 subclass from the initial IgG subclasses that are involved in a special pathophysiologic cascade, resulting in proteinuria and nephrotic syndrome.

With the identification of autoantigens, the diagnosis and prognosis paradigm of PMN has shifted to be more accurate and noninvasive. Serum autoantibody titer works better than the traditional urine protein. However, 1) the critical events involved in the autoantigen modification, autoantibody secretion, immune complex formation, basement membrane destruction, and treatment monitoring remain elusive. We also need more insights on 2) the triggers of this autoimmune disease besides air pollution, 3) the 10% of PMN caused by unknown autoantigens, 4) the mechanisms underlying the IgG4 subclass switching and its unique role in the downstream pathophysiology. What’s more, 5) regarding the anti-CD20 therapy, whether more precise B cell subset depletion and rebuilding will benefit the patients and maintain longer remission is also an important area for us to explore.

In sum, in this Research Topic, we will focus on the mentioned challenges in PMN, particularly the immunoregulation in the occurrence and development of PMN, with the attempt to shed new light on the diagnosis, treatment monitoring, and prognosis.