Abstract 17293: Human Leukocyte Antigen-G Polymorphisms Association to Post Heart Transplant Donor Specific Antibodies
Introduction: Human Leukocyte Antigen (HLA)-G is a natural immune regulator that inhibits T cells, NK cells and B cell activity. In the context of transplantation, less rejection and better graft outcomes are associated with higher serum levels of HLA-G. The association between HLA-G polymorphisms in the recipient and donor and post-transplant donor specific antibodies (DSA) has never been explored. DSA can lead to antibody-mediated rejection and are associated with worse outcomes. Objective: to determine the association between HLA-G single nucleotide polymorphisms (SNPs) in the recipient and donor and DSA.
Methods: 251 adult heart recipients and 196 matching donors were evaluated for various HLA-G SNPs. Serum from patient and donor were tested for positive presence of HLA Class I antibodies. DNA was genotyped for 14bp INDEL, G*01:01, G*01:04 and G*0:05N. The analysis was performed first in univariable regression models and then in multivariable regression model using a backward selection approach of potential risk factors with a univariable associations with p-value <0.10. The model automatically included time since transplantation as an obligatory covariate.
Results: General characteristics: recipient age 48.2±12.1 years, 69% males and donor age 35.5±14.3 years. Of those, 19 (8%) had at least one positive DSA diagnosis. In a multivariable analysis adjusted for time since transplant, documented non-compliance and blood group A, the presence of donor G*01:04 allele was identified with a protective role for the development of DSA (0.079, CI 0.02-0.39, p= 0.002). Patient allele G*01:05N was associated with increased risk for DSA (12.95, CI 2.36-71.00, p= 0.003). Lastly, donor SNP 14bp (DEL vs INDEL/INS) was independently associated as a risk factor for DSA (5.75, CI 1.70-19.36, p= 0.005).
Conclusions: Three SNPs from the donor and recipient were identified to influence the development of donor specific antibodies. This is the first study to investigate the association of HLA-G to the development of donor specific antibodies and to demonstrate both detrimental and beneficial roles for HLA-G polymorphisms.
Author Disclosures: J. Lazarte: None. L. Goldraich: None. C. Manlhiot: None. H. Kawajiri: None. L. Grosman-Rimon: None. A. Ghashghai: None. V. Rao: None. D. Delgado: None.
- © 2015 by American Heart Association, Inc.