A Distinct Glomerular Complement Deposition Pattern in Transplant Glomerulopathy

P. Verghese, R. Reed, A. Matas, Y. Kim.

University of Minnesota, Minneapolis.

Meeting: 2015 American Transplant Congress

Abstract number: B99

Keywords: Graft failure, HLA antibodies, Kidney transplantation

While many patients with transplant glomerulopathy (TG) have donor-specific antibodies, the lack of C4d deposition in the peritubular capillaries (ptc-C4d) in some cases has caused the role of complement in the pathogenesis of TG to be debated. Random frozen sections from 25 cases with and 25 cases without TG were retrieved and light microscopy (LM) and immunofluorescence were reviewed independently by 2 separate nephro-pathologists. Nine biopsies were excluded due to inadequate samples and glomerular complement deposition was assessed in all included biopsies. LM evaluation of the included specimens was classified as per Banff criteria, donor specific antibodies (DSA) to Class I and II HLA antigen was determined at time of biopsy.

Pathologic and immunologic features of biopsies with and without transplant glomerulopathy (TG)

	TG (n=23)	NON-TG (n=18)	P value
Light Microscopy Results
g
0	2	7
1	5	9
2	10	1	0.002
3	6	1
ptc
0	7	17
1	11	1	<0.001
2	3	0
3	2	0
cg
0	0	18
1	1	0	<0.001
2	1	0
3	21	0
Immunofluorescence Results
ptc C4d+	17 (74%)	6 (33%)	0.03
ptc C3d+	7 (30%)	1 (6%)	0.18
Double linear glomerular C4d+	23 (100%)	0	<0.0001
Double linear glomerular C3d+	23 (100%)	0	<0.0001
Post-Transplant Donor Specific Antibodies (DSA)
Any DSA	10 (63%)	4 (22%)	0.02
Class I DSA alone	0	1 (6%)	0.35
Class II DSA alone	4 (25%)	2 (11%)	0.30
Both	6 (38%)	1 (6%)	0.02
Simultaneous Banff Diagnosis of Rejection
ACR	0	1 (6%)
AMR	10 (43%)	0	0.0008
Previous Biopsy Proven Diagnosis of Rejection
None	70 (30%)	16 (89%)
Previous ACR	2 (9%)	1 (6%)
Previous AMR	3 (13%)	0	0.002
Mixed	1 (4%)	0

Glomerular C3d and C4d deposition occurred in a distinct pattern in all TG biopsies: segmental or global double linear staining of the glomerular capillary wall in 23 (100%) (p<0.0001) with associated endothelial pattern staining of the glomerular capillary wall in 7/23 (30%). These patterns were not present in NON-TG biopsies. The distinct glomerular complement deposition patterns in all TG cases are suggestive that TG is a complement-mediated process. Research into therapies to prevent TG should perhaps be focused on proximal complement cascade inhibition.

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