TY - JOUR
T1 - Failure to remove de novo donor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss - a retrospective study
AU - Cioni, Michela
AU - Nocera, Arcangelo
AU - Tagliamacco, Augusto
AU - Basso, Sabrina
AU - Innocente, Annalisa
AU - Fontana, Iris
AU - Magnasco, Alberto
AU - Trivelli, Antonella
AU - Klersy, Catherine
AU - Gurrado, Antonella
AU - Ramondetta, Miriam
AU - Boghen, Stella
AU - Catenacci, Laura
AU - Verrina, Enrico
AU - Garibotto, Giacomo
AU - Ghiggeri, Gian Marco
AU - Cardillo, Massimo
AU - Ginevri, Fabrizio
AU - Comoli, Patrizia
PY - 2019/1
Y1 - 2019/1
N2 - Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P <0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P <0.05), but not C1q-binding, and high mean fluorescence intensity (P <0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.
AB - Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low-dose IVIG + Rituximab or high-dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow-up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P <0.001) and presence of C3d-binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti-humoral treatment. In the multivariable analysis, C3d-binding ability (P <0.05), but not C1q-binding, and high mean fluorescence intensity (P <0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high-MFI DSAs.
KW - anti-humoral therapy
KW - antibody-mediated rejection
KW - complement-binding DSA
KW - de novo donor-specific anti-HLA antibodies
KW - pediatric kidney transplantation
KW - Adolescent
KW - Antibodies
KW - Biopsy
KW - Child
KW - Female
KW - Follow-Up Studies
KW - Graft Rejection/immunology
KW - Graft Survival/immunology
KW - HLA Antigens/immunology
KW - Humans
KW - Isoantibodies/immunology
KW - Kidney/immunology
KW - Kidney Transplantation
KW - Male
KW - Multivariate Analysis
KW - Prognosis
KW - Retrospective Studies
KW - Risk
KW - Rituximab/administration & dosage
KW - Tissue Donors
U2 - 10.1111/tri.13325
DO - 10.1111/tri.13325
M3 - Article
VL - 32
SP - 38
EP - 48
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 1
ER -