LAUSR

Dear Editors, We were very pleased to have read the Epub ahead of print of a Transplant International’s article entitled “glomerular C4d deposits can mark structural capillary wall remodeling in thrombotic microangiopathy and transplant glomerulopathy: C4d beyond active antibody-mediated injury: a retrospective study” (Fig. 1). Until now, no studies have reported on the importance of using glomerular C4d staining in the evaluation of ultrastructural changes of the glomerular basement membrane. Dr. Gasim and colleagues from Chapel Hill describe very nicely that the presence of pseudolinear C4d positivity along the glomerular basement membrane (GBM) can be associated with ultrastructural changes of the capillary walls. Indeed, we too use the presence of pseudolinear GBM-C4d immunohistochemical staining (IHC), in particular if seen in isolation not accompanied by C4d staining along peritubular capillaries (PTCs), as an indication for underlying structural GBM abnormalities and detailed further electron microscopic analyses: isolated GBM-C4d, an alarm signal for trouble along glomerular capillary walls! As is described in Dr. Gasim’s article, in those renal biopsies in which we find pseudolinear positivity of C4d along the GBM by IHC, even if it is scant, we frequently detect in corresponding electron microscopic studies underlying alterations of the GBM (Fig. 1a and b). Since in such cases significant hematuria and proteinuria may be absent, the detection of pseudolinear GBM-C4d can be the only sign marking the necessity for further electron microscopic analyses that might be skipped otherwise. The flowchart presented in Fig. 4 of Dr. Gasim’s article very nicely brings matters to the point. It highlights that pseudolinear C4d along the GBM, especially in the absence of corresponding staining along ptcs (and often seen in the absence of detectable circulating donor-specific antibodies), can be attributed to structural remodeling of glomerular capillary walls rather than active/acute antibody-mediated rejection. Thus, we fully concur with the “Chapel Hill observations”: glomerular