Membranous nephropathy is developed under Th2 environment in chronic graft-versus-host disease

SummaryClinical data from case reports of nephrotic syndrome including allogenetic hematopoietic stem cell transplantation (HSCT) suggest that there may be some relationship between chronic graft-versus-host disease (GVHD) and membranous nephropathy (MN). It is widely recognized T cells are crucial for the development of GVHD, and that T helper (Th) cells differentiate into at least two subsets, Th1 and Th2. The polarized situation between Th1 and Th2 cells is established to be important in animal models and human autoimmune diseases. In a chronic GVHD murine model a Th2 cell plays a pivotal role for the pathogenesis. In MRL/lpr mice, which is particularly valuable model for systemic lupus erythematosus, developed diffuse proliferative glomerulonephritis (DPGN) in Th1 environment and MN in Th2 environment. Similarly, Th2 cells may be predominantly activated in chronic GVHD, production and deposition of IgG4 in the glomeruli may develop MN.A hypothesis is: when the patient in period of chronic GVHD developed immune complex-mediated disease, IgG4 might be mainly produced in Th2 environment, and the deposition of IgG4 in the glomeruli may result in the formation of MN.