HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients.
BACKGROUND
Although evidence links HLA allele mismatching to worse outcomes in pediatric heart transplantation, no studies to our knowledge have applied the quantification of structural HLA differences between donor and recipient to risk evaluation. We examine the association between molecular-level HLA mismatching and long-term graft loss in pediatric recipients of heart transplants.


METHODS
HLA Matchmaker was used to quantify the number of mismatched class-specific HLA eplets among 4,851 heart transplant recipients ≤18 years of age in the Scientific Registry of Transplant Recipients (1987-2012). Survival analysis was used to compare long-term probabilities of graft loss by number of eplet mismatches and allele mismatches stratified by eplet mismatches.


RESULTS
Recipients with 10 to 20 or >20 class I (HLA-A and HLA-B) eplet mismatches experienced increased long-term graft loss compared with recipients with <10 class I eplet mismatches (adjusted hazard ratio = 1.23 [95% confidence interval = 1.06-1.42], adjusted hazard ratio = 1.27 [95% confidence interval = 1.08-1.50], respectively). Recipients with 2 to 4 class I allele mismatches had increased long-term graft loss compared with recipients with 0 to 1 class I allele mismatches. Neither class II (HLA-DR) eplet mismatching nor class II allele mismatching was associated with graft loss. On stratification by allele and structural eplet mismatching, only recipients with 2 to 4 class I allele mismatches and ≥10 class I eplet mismatches had an increased probability of graft loss compared with recipients with 0 to 1 class I allele mismatches (adjusted hazard ratio = 1.42 [95% confidence interval = 1.09-1.57]).


CONCLUSIONS
Molecular-level HLA mismatching may aid in identifying recipients at increased risk of long-term graft loss who could benefit from intensified post-transplant surveillance and management.
Division of Pediatric Cardiology, Children's Hospital Los Angeles, Los Angeles, California. Electronic address: Patrick.morris.sullivan@gmail.com.
Patrick M
PM
Sullivan
Immunogenetics/HLA Laboratory, Puget Sound Blood Center, Seattle, Washington.
Paul
P
Warner
Division of Pediatric Cardiology, Seattle Children's Hospital, Seattle, Washington.
Mariska S
MS
Kemna
Division of Pediatric Cardiology, Seattle Children's Hospital, Seattle, Washington.
Erin L
EL
Albers
Division of Pediatric Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
Sabrina P
SP
Law
Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
Noel S
NS
Weiss
Division of Pediatric Cardiology, Seattle Children's Hospital, Seattle, Washington.
Yuk M
YM
Law
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D016027:Heart Transplantation; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012189:Retrospective Studies; D066027:Transplant Recipients
D000939:Epitopes; D015235:HLA-B Antigens
HLA; HLA matchmaker; epitope; graft loss; heart transplantation; pediatric