Impact of antibodies against human leukocyte antigens on long-term outcome in pediatric heart transplant patients: an analysis of the United Network for Organ Sharing database.
OBJECTIVE
Controversy exists regarding the importance of circulating antibodies as determined by panel-reactive antibody screening as a risk factor for graft failure in pediatric patients undergoing heart transplantation. This study sought to determine the association of elevated anti-human leukocyte antibodies with long-term survival in pediatric heart transplant patients.


METHODS
The United Network for Organ Sharing registry was queried for pediatric patients (aged < 18 years at listing) with panel-reactive antibody levels obtained before heart transplantation from 1987 through 2004. Survival analysis methods were used to assess the association of elevated panel-reactive antibodies with long-term graft and patient survival.


RESULTS
Panel-reactive antibodies were obtained before transplantation from 3534 patients, median age 4 years (interquartile range 0-12 years). Most, 2711 (77%), had no detectable panel-reactive antibodies, 436 (12%) had panel-reactive antibodies of 1% to 10%, and 387 (11%) had panel-reactive antibodies greater than 10%. Patients with panel-reactive antibodies greater than 10% were more likely to be older (P = .04), have congenital heart disease (P < .001), and have a longer wait list time (P = .006). Patients with panel-reactive antibodies greater than 10% had significantly worse graft survival and patient survival than did patients with undetectable panel-reactive antibodies and panel-reactive antibodies of 1% to 10% (P < .05 for all). Controlling for confounding variables, elevated panel-reactive antibodies as a continuous variable and panel-reactive antibodies greater than 10% as a categorical variable were independently associated with decreased graft survival (P = .04 and P = .02, respectively).


CONCLUSIONS
Elevated panel-reactive antibodies are independently associated with worse long-term graft survival in pediatric patients undergoing heart transplantation. Further study is needed to determine the optimal management of this high-risk population.
Department of Pediatrics, Lillie Frank Abercrombie Section of Pediatric Cardiology, Baylor College of Medicine, Texas Children's Hospital, Houston, Tex 77030, USA. jrossano@bcm.tmc.edu
Joseph W
JW
Rossano
David L S
DL
Morales
Farhan
F
Zafar
Susan W
SW
Denfield
Jeffrey J
JJ
Kim
John L
JL
Jefferies
William J
WJ
Dreyer
D000906:Antibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D009927:Tissue and Organ Procurement / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
D000906:Antibodies; D006680:HLA Antigens