Sánchez Zapardiel, Elena Castro Panete, María José Mancebo Sierra, Esther Morales Pérez, Pablo Laguna Goya, Rocío Morales Cerdán, José María Apaza Chávez, Jacqueline Andrés Belmonte, Amado Talayero Giménez de Azcárate, Paloma Paz Artal, Estela
Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity. [artículo] - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2016 - 31(1):150-60.
Formato Vancouver:
Sánchez Zapardiel E, Castro Panete MJ, Mancebo E, Morales P, Laguna Goya R, Morales JM et al. Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity. Nephrol Dial Transplant. 2016 Jan;31(1):150-60.
PMID: 26323481
Contiene 30 referencias
Background: We previously reported that preformed anti-MHC class I-related chain A (MICA) antibodies increase the risk for renal graft rejection and enhance the deleterious effect of PRA(+) status early after transplantation.
Methods: We studied 727 kidney recipients. Days to reach optimal serum creatinine level, estimated glomerular filtration rate (eGFR) at Month 3 and chronic kidney disease (CKD) stages were recorded. Anti-MICA specificities and C1q binding were tested by solid-phase assay. Complement-dependent cytotoxicity (CDC) and flow cytometry (FC) cross-matches with HeLa and PMA/CD28-T-blasts were performed.
Results: PRA(+)MICA(+) recipients exhibited longer time to reach optimal serum creatinine level after transplantation (P = 0.005) and had the lowest eGFR at Month 3 (P = 0.006). PRA(+)MICA(+) status independently increased the risk for CKDT stage 5 at Month 3 [hazard ratio (HR) 4.92, P = 0.030]. Pre-transplant anti-MICA antibodies were polyspecific and showed stronger reactions when coexisting with anti-HLA antibodies (mean standard fluorescent intensity 112 157 ± 44 426 in HLA(+)MICA(+) sera versus 49 680 ± 33 116 in HLA(-)MICA(+) sera, P = 0.0006). Anti-AYVE supereplet reactivity was significantly higher in HLA(+)MICA(+) versus HLA(-)MICA(+) patients (P < 0.001) and significantly superior than anti-CMGWS supereplet within HLA(+)MICA(+) patients (P = 0.001). Three of 13 anti-MICA(+) pre-transplant sera were positive for the C1q binding assay; one of them (serum 3) exclusively recognized AYVE supereplet with a strong reactivity against MICA*027 antigen (same as MICA*008). Anti-MICA antibodies in anti-HLA-absorbed serum 3 bound native MICA molecules in MICA*008(+) HeLa and PMA/CD28-T-blasts and mediated cell death by activating complement.
Conclusion: Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.
Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity. [artículo] - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2016 - 31(1):150-60.
Formato Vancouver:
Sánchez Zapardiel E, Castro Panete MJ, Mancebo E, Morales P, Laguna Goya R, Morales JM et al. Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity. Nephrol Dial Transplant. 2016 Jan;31(1):150-60.
PMID: 26323481
Contiene 30 referencias
Background: We previously reported that preformed anti-MHC class I-related chain A (MICA) antibodies increase the risk for renal graft rejection and enhance the deleterious effect of PRA(+) status early after transplantation.
Methods: We studied 727 kidney recipients. Days to reach optimal serum creatinine level, estimated glomerular filtration rate (eGFR) at Month 3 and chronic kidney disease (CKD) stages were recorded. Anti-MICA specificities and C1q binding were tested by solid-phase assay. Complement-dependent cytotoxicity (CDC) and flow cytometry (FC) cross-matches with HeLa and PMA/CD28-T-blasts were performed.
Results: PRA(+)MICA(+) recipients exhibited longer time to reach optimal serum creatinine level after transplantation (P = 0.005) and had the lowest eGFR at Month 3 (P = 0.006). PRA(+)MICA(+) status independently increased the risk for CKDT stage 5 at Month 3 [hazard ratio (HR) 4.92, P = 0.030]. Pre-transplant anti-MICA antibodies were polyspecific and showed stronger reactions when coexisting with anti-HLA antibodies (mean standard fluorescent intensity 112 157 ± 44 426 in HLA(+)MICA(+) sera versus 49 680 ± 33 116 in HLA(-)MICA(+) sera, P = 0.0006). Anti-AYVE supereplet reactivity was significantly higher in HLA(+)MICA(+) versus HLA(-)MICA(+) patients (P < 0.001) and significantly superior than anti-CMGWS supereplet within HLA(+)MICA(+) patients (P = 0.001). Three of 13 anti-MICA(+) pre-transplant sera were positive for the C1q binding assay; one of them (serum 3) exclusively recognized AYVE supereplet with a strong reactivity against MICA*027 antigen (same as MICA*008). Anti-MICA antibodies in anti-HLA-absorbed serum 3 bound native MICA molecules in MICA*008(+) HeLa and PMA/CD28-T-blasts and mediated cell death by activating complement.
Conclusion: Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.
