Glomerular C4d deposits can mark structural capillary wall remodelling in thrombotic microangiopathy and transplant glomerulopathy: C4d beyond active antibody‐mediated injury: a retrospective study |
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| Authors: | Adil H. Gasim Jamie S. Chua Ron Wolterbeek John Schmitz Eric Weimer Harsharan K. Singh Volker Nickeleit |
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| Affiliation: | 1. Division of Nephropathology, Department of Pathology and Laboratory Medicine, The University of North Carolina School of Medicine, Chapel Hill, NC, USA;2. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;3. Department of Medical Statistics and Bio‐Informatics, Leiden University Medical Center, Leiden, The Netherlands;4. Department of Pathology and Laboratory Medicine, McLendon Clinical Laboratories, The University of North Carolina School of Medicine, Chapel Hill, NC, USA |
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| Abstract: | Peritubular capillary C4d (ptc‐C4d) usually marks active antibody‐mediated rejection, while pseudolinear glomerular capillary C4d (GBM‐C4d) is of undetermined diagnostic significance, especially when seen in isolation without concurrent ptc‐C4d. We correlated GBM‐C4d with structural GBM abnormalities and active antibody‐mediated rejection in 319 renal transplant and 35 control native kidney biopsies. In kidney transplants, ptc‐C4d was associated with GBM‐C4d in 97% by immunofluorescence microscopy (IF) and 61% by immunohistochemistry (IHC; P < 0.001). Transplant glomerulopathy correlated with GBM‐C4d (P < 0.001) and presented with isolated GBM‐C4d lacking ptc‐C4d in 69% by IF and 40% by IHC. Strong isolated GBM‐C4d was found post year‐1 in repeat biopsies with transplant glomerulopathy. GBM‐C4d staining intensity correlated with Banff cg scores (rs = 0.45, P < 0.001). Stepwise exclusion and multivariate logistic regression corrected for active antibody‐mediated rejection showed significant correlations between GBM duplication and GBM‐C4d (P = 0.001). Native control biopsies with thrombotic microangiopathies demonstrated GBM‐C4d in 92% (IF, P < 0.001) and 35% (IHC). In conclusion, pseudolinear GBM‐C4d staining can reflect two phenomena: (i) structural GBM changes with duplication in native and transplant kidneys or (ii) active antibody‐mediated rejection typically accompanied by ptc‐C4d. While ptc‐C4d is a dynamic ‘etiologic’ marker for active antibody‐mediated rejection, isolated strong GBM‐C4d can highlight architectural glomerular remodelling. |
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| Keywords: | complement factor C4d electron microscopy glomerular basement membrane duplication immunofluorescence microscopy thrombotic microangiopathy transplant glomerulopathy |
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