TY - JOUR
T1 - Acquisition of C3d-Binding Activity by De Novo Donor-Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients
AU - Comoli, P.
AU - Cioni, M.
AU - Tagliamacco, A.
AU - Quartuccio, G.
AU - Innocente, A.
AU - Fontana, I.
AU - Trivelli, A.
AU - Magnasco, A.
AU - Nocco, A.
AU - Klersy, C.
AU - Rubert, L.
AU - Ramondetta, M.
AU - Zecca, M.
AU - Garibotto, G.
AU - Ghiggeri, G. M.
AU - Cardillo, M.
AU - Nocera, A.
AU - Ginevri, F.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity. Overall, 39 patients developed dnDSAs, which were C1q+ and C3d+ in 25 and nine patients, respectively. At follow-up, progressive acquisition over time of dnDSA C1q and C3d binding ability, within the same antigenic specificity, was observed, paralleled by an increase in mean fluorescence intensity that correlated with clinical outcome. C3d-fixing dnDSAs were better fit to stratify graft loss risk when the different dnDSA categories were evaluated in combined models because the 10-year graft survival probability was lower in patients with C3d-binding dnDSA than in those without dnDSAs or with C1q+/C3d− or non-complement-binding dnDSAs (40% vs. 94%, 100%, and 100%, respectively). Based on the kinetics profile, we favor dnDSA removal or modulation at first confirmed positivity, with treatment intensification guided by dnDSA biological characteristics.
AB - Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity. Overall, 39 patients developed dnDSAs, which were C1q+ and C3d+ in 25 and nine patients, respectively. At follow-up, progressive acquisition over time of dnDSA C1q and C3d binding ability, within the same antigenic specificity, was observed, paralleled by an increase in mean fluorescence intensity that correlated with clinical outcome. C3d-fixing dnDSAs were better fit to stratify graft loss risk when the different dnDSA categories were evaluated in combined models because the 10-year graft survival probability was lower in patients with C3d-binding dnDSA than in those without dnDSAs or with C1q+/C3d− or non-complement-binding dnDSAs (40% vs. 94%, 100%, and 100%, respectively). Based on the kinetics profile, we favor dnDSA removal or modulation at first confirmed positivity, with treatment intensification guided by dnDSA biological characteristics.
KW - alloantibody
KW - clinical research/practice
KW - immunobiology
KW - immunosuppression/immune modulation
KW - kidney (allograft) function/dysfunction
KW - kidney transplantation/nephrology
KW - monitoring: immune
KW - rejection: antibody-mediated (ABMR)
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U2 - 10.1111/ajt.13700
DO - 10.1111/ajt.13700
M3 - Article
C2 - 26725780
AN - SCOPUS:84976464893
VL - 16
SP - 2106
EP - 2116
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 7
ER -