title: The clinical impact of humoral immunity in pediatric renal transplantation.
abstract: 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. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 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 donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.
authors: Department of Pediatrics, Stanford University, Stanford, California, USA.
authors: Abanti
authors: A
authors: Chaudhuri
authors: Mikki
authors: M
authors: Ozawa
authors: Matthew J
authors: MJ
authors: Everly
authors: Robert
authors: R
authors: Ettenger
authors: Vikas
authors: V
authors: Dharnidharka
authors: Mark
authors: M
authors: Benfield
authors: Robert
authors: R
authors: Mathias
authors: Anthony
authors: A
authors: Portale
authors: Ruth
authors: R
authors: McDonald
authors: William
authors: W
authors: Harmon
authors: David
authors: D
authors: Kershaw
authors: V Matti
authors: VM
authors: Vehaskari
authors: Elaine
authors: E
authors: Kamil
authors: H Jorge
authors: HJ
authors: Baluarte
authors: Bradley
authors: B
authors: Warady
authors: Li
authors: L
authors: Li
authors: Tara K
authors: TK
authors: Sigdel
authors: Szu-chuan
authors: SC
authors: Hsieh
authors: Hong
authors: H
authors: Dai
authors: Maarten
authors: M
authors: Naesens
authors: Janie
authors: J
authors: Waskerwitz
authors: Oscar
authors: O
authors: Salvatierra
authors: Paul I
authors: PI
authors: Terasaki
authors: Minnie M
authors: MM
authors: Sarwal
mesh_terms: D002648:Child; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A