The clinical impact of humoral immunity in pediatric renal transplantation

Abanti Chaudhuri, Mikki Ozawa, Matthew J. Everly, Robert Ettenger, Vikas Dharnidharka, Mark Benfield, Robert Mathias, Anthony Portale, Ruth McDonald, William Harmon, David Kershaw, V. Matti Vehaskari, Elaine Kamil, H. Jorge Baluarte, Bradley Warady, Li Li, Tara K. Sigdel, Szu Chuan Hsieh, Hong Dai, Maarten NaesensJanie Waskerwitz, Oscar Salvatierra, Paul I. Terasaki, Minnie M. Sarwal

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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 serumanti-HLA antibodies to donorHLA 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 toHLA andMICA 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.

Original languageEnglish
Pages (from-to)655-664
Number of pages10
JournalJournal of the American Society of Nephrology
Volume24
Issue number4
DOIs
StatePublished - Mar 29 2013

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