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 lowrisk 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 (donorspecific 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.

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…A similar association has now been shown in children, demonstrating that the detection of DSAs is associated with impaired graft survival [58]. Interestingly, Chaudhuri et al observed that non-HLA antibodies, such as MICA antibodies, were also associated with subsequent worsening graft function [59]. The underlying trial was a steroidavoidance study, and unexpectedly, the amount of DSAs detected was higher in the steroid group than in the group not receiving steroids.…”

Prevalence, Incidence and Risk Factors for Donor-Specific Anti-HLA Antibodies in Maintenance Liver Transplant Patients

“…The difference observed between Fontana et al's (15) study and ours is probably because we used a more sensitive assay. Recently, Miyagawa-Hayashino et al (16) assessed the prevalence of DSAs among stable pediatric LT patients who had survived for >5 years: they found a prevalence of 48% at 11 years (min-max: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] posttransplantation. This high prevalence of DSAs is probably related to the very long follow-up in this Japanese study (16).…”

Kidney Transplantation in Children

“…67 Reemerging B cells appeared to be naive, immature, and more regulatory in children than in adults. 66 By 3 to 5 years after transplantation, new antibodies directed against HLA antigens developed in 25% of children, 68 as compared with only 10% of adults. 69 Identification of relatively noninvasive biomarkers of acute rejection that might replace transplant biopsy is important.…”