TY - JOUR
T1 - Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection
AU - Chang, Anthony
AU - Moore, Jocelyn M.
AU - Cowan, Michelle L.
AU - Josephson, Michelle A.
AU - Chon, W. James
AU - Sciammas, Roger
AU - Du, Zeying
AU - Marino, Susana R.
AU - Meehan, Shane M.
AU - Millis, Michael
AU - David, Michael Z.
AU - Williams, James W.
AU - Chong, Anita S.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - allograft rejection
KW - B cells
KW - immunohistochemistry
KW - plasma cells
UR - http://www.scopus.com/inward/record.url?scp=84866269293&partnerID=8YFLogxK
U2 - 10.1111/j.1432-2277.2012.01531.x
DO - 10.1111/j.1432-2277.2012.01531.x
M3 - Article
C2 - 22805456
AN - SCOPUS:84866269293
SN - 0934-0874
VL - 25
SP - 1050
EP - 1058
JO - Transplant International
JF - Transplant International
IS - 10
ER -