Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection.
The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3(+) T cells as the dominant cell type, followed by CD20(+) B cells and CD138(+) plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B-cell density trended toward significance. Surprisingly T-cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ≥6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid-resistant acute rejection.
Departments of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA. anthony.chang@uchospitals.edu
Anthony
A
Chang
Jocelyn M
JM
Moore
Michelle L
ML
Cowan
Michelle A
MA
Josephson
W James
WJ
Chon
Roger
R
Sciammas
Zeying
Z
Du
Susana R
SR
Marino
Shane M
SM
Meehan
Michael
M
Millis
Michael Z
MZ
David
James W
JW
Williams
Anita S
AS
Chong
D000328:Adult; D018951:Antigens, CD20 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy / Q000379:methods; D017252:CD3 Complex / Q000096:biosynthesis; D015935:Complement C4b / Q000096:biosynthesis; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis; D010950:Plasma Cells / Q000166:cytology*; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000628:therapy*; D053668:Syndecan-1 / Q000096:biosynthesis; D014184:Transplantation, Homologous
D018951:Antigens, CD20; D017252:CD3 Complex; D010446:Peptide Fragments; D053668:Syndecan-1; D015935:Complement C4b; C032261:complement C4d