In some cases membranous nephropathy is associated with other diseases; however, the association of the diseases might be coincidental and actually in the instances of true secondary membranous nephropathy, very little data exist on how the underlying disease prospects to formation of immune deposits. humans, whether it is the re-formation of circulating immune complexes or the formation by binding of circulating antibodies to a target antigen within the podocyte surface remained a matter of conversation for many years. A first confirmation that immune complex formation is definitely induced by binding of circulating antibodies to a podocytic antigen and prospects to the development of membranous nephropathy in humans arrived in 2002 (Debiec et al., 2002). Transplacental transport of antibodies against neutral endopeptidase from your mother to the fetus led to membranous nephropathy in the newborn. However, antibodies to neutral endopeptidase were not found to be responsible for the initiation of membranous nephropathy in adults. The major breakthrough in elucidating the pathophysiology of membranous nephropathy came with the recognition of the PLA2R as the prospective antigen in 70% of individuals with membranous nephropathy (Beck et al., 2009). Circulating PLA2R antibodies bind to the podocytic PLA2R antigen leading to immune deposit formation and membranous nephropathy. While confirming the formation of immune complexes in these individuals, these findings lead to more questions about the genesis of membranous nephropathy, most importantly, how the disease develops in PLA2R antibody bad patients. In some of these individuals, THSD7A was identified as the podocytic target antigen with circulating antibodies against THSD7A (Tomas et al., 2014). These findings show that more than one podocytic antigen is present, and circulating antibodies against these antigens lead to membranous nephropathy. It is right BQ-123 now obvious that membranous nephropathy may have different pathologic backgrounds in individual individuals. The understanding how the disease develops is definitely of outmost importance in order to develop fresh, specific treatment options. This is also important in individuals with membranous nephropathy, who are bad for PLA2R and THSD7A antibodies. In some cases membranous nephropathy is definitely associated with additional diseases; however, the association of the diseases might be coincidental and actually in the instances of true secondary membranous nephropathy, very little data exist on how the underlying disease prospects to formation of immune deposits. The work of Buelli et al. elucidates a possible BQ-123 mechanism of disease development in individuals with IgG4-related disease and membranous nephropathy. The hypothesis of the authors suggests a two-step model of disease induction, where an antibody-independent or an antibody-induced Rabbit Polyclonal to MRPS16 podocytic lesion associated with IgG4-related disease results in the formation of podocytic neoantigens. These findings are important in several aspects and might have an impact on patient management, should they become confirmed em in vivo /em . First, they shed more light on the relationship of IgG4-related disease to membranous nephropathy, suggesting that the two diseases are not merely coincidental. At the same time, this work points to another key query in the field: what is the role of these neoantigens in disease development, perpetuation or remission? This is important for patient care, because it may lead to the development of more specific treatment options and fresh biomarkers for disease activity and BQ-123 treatment response. To confirm such a hypothesis long term studies will need to show that circulating antibodies against BQ-123 SOD2 are in fact present and persist in individuals with membranous nephropathy and how they relate to disease activity over time. The clinical experience of individuals with PLA2R-associated membranous nephropathy already demonstrates the discovery of this antigen affects individual care (Hoxha et al., 2014). Further research within the pathomechanisms of membranous nephropathy should therefore also focus on the aim to accomplish tailored treatment options, dealing with the issue of the need of an immunosuppressive therapy, versus BQ-123 supportive treatment without immunosuppression, which still has a quantity of severe side effects. Disclosure The authors declare no conflicts of interest..
