Identifying the “permeability factor” for patients with FSGS or minimal change disease has been one of the “holy grails” of nephrology, and our inability to identify such a factor has not been for any lack of trying. One of the obstacles in studying this disease is the lack of good animal models to study it.
A French group published a 2007 JASN article describing a mouse model of immune-mediated nephrotic syndrome which perhaps gives us some mechanistic insight into the cause of the disease. In this paper, researchers took CD34+ T-cells from humans with steroid-resistant nephrotic syndrome. They then injected these T-cells either (a) intraperitoneally, or (b) intraosseously–that is, directly into the bone marrow. In the case of intraperitoneal injections, the existence of circulating “humanized” T-cells could be demonstrated, but they eventually went away over time as the engraftment was not permanent. These mice did not get proteinuria. In the case of intraosseous injections, these T-cells could be demonstrated to engraft permanently, albeit at a low frequency. Interestingly, these mice developed significant albuminuria and foot process effacement, suggesting that this could be used as a mouse model of disease.
What is particularly interesting about this experiment is the idea that the “permeability factor” is transferable only with T-cell precursors–and not with peripheral T-cells. So perhaps the permeability factor comes from the bone marrow, rather than activated T-cell responses…
