C3 glomerular diseases and dense deposit disease, novel entities that have been successfully treated now with eculizumab. A recent article in JASN summarizes what we see on kidney biopsies in cases that have been successfully treated with eculizumab. C3 glomeluar disease is manifested like MPGN pattern of injury but mainly with c3 deposits and no significant Ig staining.
The researchers found:
1. One year post treatment biopsies still showed no reduction in C3 or C5b-9 and EM showing deposits still being present( they postulate this being from long half lives).
2. Interestingly, all biopsies showed new denovo monoclonal staining for IgG-kappa in the same distribution as C3 and C5b-9, like a monoclonal deposition disease and paraprotein disease.
3. Staining of the Y heavy chain was restricted to the IgG2 and IgG4 subclasses.
This is interesting as by the new IF based definition of MPGN pattern, C3 glomerularopathy is defined by no IF staining for Ig. After treated, most of these cases showed staining for Ig. The investigators suggest this might be a monoclonal binding of the eculizumab antibody itself due to an inflammatory response. The staining was exclusive in IgG2, IgG4 and kappa and the authors propose that this is exactly what would be detected if eculizumab were being deposited in tissues. Even a case of aHUS who got this drug showed this finding post treatment( with no prior EM deposits).
It appears that this drug binds and deposits within glomeruli, thin basement membrane and vessel walls of treated patients and results in this pattern of Ig that the investigators are seeing. This should be careful put in the differential when we biopsy someone who had eculizumab in the past and not call this MIDD or new signs of paraprotein mediated disease. Presumably, a bone marrow would have been negative in theses cases.
For the full paper look at
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