De Novo Membranous Glomerulonephritis Is Associated with C4d Depostion in Peritubular Capillaries and Basement Membrane Multilamination: Putative Variant of Chronic Humoral Rejection
AB Collins, AB Farris, W Wong, S Saidman, N Tolkoff-Rubin, NB Goes, DS Ko, AB Cosimi, RB Colvin. Massachusetts General Hospital, Boston, MA
Background: The pathogenesis of de novo MGN in renal allografts is unknown. Animal studies support a role for non-MHC glomerular alloantigens. In a recent case report, the onset of de novo MGN correlated with development of anti-donor specific antibodies (DSA). Here we test the hypothesis that de novo MGN is a variant of chronic humoral rejection.
Design: All cases of de novo MGN and other forms of glomerular disease with available tissue were studied from transplant biopsies (1997-2008), C4d deposition (immunofluorescence) and electron microscopy. During this time C4d+ CHR was diagnosed on 8.4% of 738 transplant biopsies.
Results: De novo MGN had a higher frequency of C4d+ than the other de novo GN combined (p=0.017). Only de novo hepatitis C virus (HCV) GN was associated with C4d. Recurrent MGN and HCV were not statistically different from de novo. C4d+ de novo MGN commonly had mulitlamination of the GBM (4/4) and PTC BM (3/4), but this was not statistically greater than in C4d- de novo MGN (1/6 and 1/5 respectively; p>0.05). All de novo MGN patients tested for HLA-DSA were positive (3 class I, 1 also class II). One patient had three biopsies over 4 years all with de novo MGN, but C4d was present only in the last biopsy. One C4d- case had an earlier biopsy with focal C4d (10%).
|Diagnosis||N Pts||C4d+ PTC||%C4d+|
|De novo MGN||16||6||38%|
|De novo FSGS||15||0||0%|
|De novo IgA||4||0||0%|
|De novo HCV||5||2||40%|
|De novo Misc GN||5||0||0%|
Conclusions: C4d+ in PTC, the hallmark of CHR, is strongly associated with de novo MGN, but not other de novo GN except for that of HCV. The lack of a tight association argues that different antigens are the target of de novo MGN and CHR and fits with experimental data suggesting that non-MHC alloantigens may be the target. The association may be due to a propensity to form alloantibodies of any type or promotion of an immune response to glomerular antigens secondary to injury mediated by HLA antibodies. In any case, this study supports the concept that de novo MGN may be a variant of CHR.
Category: Kidney (does not include tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 185, Tuesday Afternoon