PURPOSE: The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood.
METHOD: Using data from 130 low-risk (peak PRA <20%) pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donorHLA antigens (donor specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and centralized, graft histology scored on protocol biopsies at 0, 6, 12, and 24 months post-transplantation.
RESULTS: We detected de novo antibodies after transplant in 24% (23% of SF group and 25%of SB group), with maximum incidence after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Correlation of antibody titers and incidence with centralized semi-quantitative, compartment scores of allograft injury (using Banff and CADI scores), we found that presence of specific antibodies de novo associated with significantly higher risk for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02).
CONCLUSION: In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, and when detected these patients have greater risk for acute and chronic rejection with risk of accelerated loss of graft function. Avoiding steroids does not modify this incidence of antibody detection or the rate of progressive histological injury or acute rejection. Serial assessments of humoral immunity after transplant may help assess immunological risk and guide individual tailoring of immunosuppression therapy.
To cite this abstract in AMA style:Sarwal M, Chadhuri A, Ozawa M, Everly M, Ettenger R, Dharnidharka V, Benfield M, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari V, Kamil E, Baluarte H, Warady B, Sigdel T, Szu-chuan H, Dai H, Naesens M, Waskerwitz J, Salvatierra O, Terasaki P. Clinical Impact and Evolution of Humoral Immunity in a Randomized Multicenter Trial of Steroid Avoidance in Pediatric Renal Transplantation, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/clinical-impact-and-evolution-of-humoral-immunity-in-a-randomized-multicenter-trial-of-steroid-avoidance-in-pediatric-renal-transplantation-the/. Accessed May 28, 2020.
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