Impact of active antibody‐mediated rejection treatment on donor‐specific antibodies in pediatric kidney transplant recipients

2019 ◽  
Vol 23 (8) ◽  
Author(s):  
Elisabeth Kincaide ◽  
Kelley Hitchman ◽  
Reed Hall ◽  
Ikuyo Yamaguchi ◽  
Yanli Ding ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Donor Specific Antibodies

CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant Recipients

2021 ◽  
Vol 32 (12) ◽  
pp. 3231-3251
Author(s):  
Baptiste Lamarthée ◽  
Carole Burger ◽  
Charlotte Leclaire ◽  
Emilie Lebraud ◽  
Aniela Zablocki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Hla Antibodies ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Biopsy Specimens ◽  
Glomerular Endothelial Cells ◽  
Donor Specific Antibodies

BackgroundAfter kidney transplantation, donor-specific antibodies against human leukocyte antigen donor-specific antibodies (HLA-DSAs) drive antibody-mediated rejection (ABMR) and are associated with poor transplant outcomes. However, ABMR histology (ABMRh) is increasingly reported in kidney transplant recipients (KTRs) without HLA-DSAs, highlighting the emerging role of non-HLA antibodies (Abs).MethodsW e designed a non-HLA Ab detection immunoassay (NHADIA) using HLA class I and II–deficient glomerular endothelial cells (CiGEnCΔHLA) that had been previously generated through CRISPR/Cas9-induced B2M and CIITA gene disruption. Flow cytometry assessed the reactivity to non-HLA antigens of pretransplantation serum samples from 389 consecutive KTRs. The intensity of the signal observed with the NHADIA was associated with post-transplant graft histology assessed in 951 adequate biopsy specimens.ResultsW e sequentially applied CRISPR/Cas9 to delete the B2M and CIITA genes to obtain a CiGEnCΔHLA clone. CiGEnCΔHLA cells remained indistinguishable from the parental cell line, CiGEnC, in terms of morphology and phenotype. Previous transplantation was the main determinant of the pretransplantation NHADIA result (P<0.001). Stratification of 3-month allograft biopsy specimens (n=298) according to pretransplantation NHADIA tertiles demonstrated that higher levels of non-HLA Abs positively correlated with increased glomerulitis (P=0.002), microvascular inflammation (P=0.003), and ABMRh (P=0.03). A pretransplantation NHADIA threshold of 1.87 strongly discriminated the KTRs with the highest risk of ABMRh (P=0.005, log-rank test). A multivariate Cox model confirmed that NHADIA status and HLA-DSAs were independent, yet synergistic, predictors of ABMRh.ConclusionThe NHADIA identifies non-HLA Abs and strongly predicts graft endothelial injury independent of HLA-DSAs.

Graft immunologic events in deceased donor kidney transplant recipients with preformed HLA-donor specific antibodies

2018 ◽  
Vol 46 ◽  
pp. 8-13 ◽  
Author(s):  
Xicohténcatl Ixtlapale-Carmona ◽  
Adriana Arvizu ◽  
Adrian De-Santiago ◽  
Norma González-Tableros ◽  
Mayra López ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Deceased Donor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Donor Kidney ◽  
Specific Antibodies ◽  
Deceased Donor Kidney ◽  
Donor Specific Antibodies ◽  
Deceased Donor Kidney Transplant
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