Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: Room 3AB
Background: De-novo donor specific antibody (DSA) is one of the strongest independent predictors of graft loss with HLA mismatching being a major risk factor for development of de-novo DSA. Recent conceptual and technical advances permit examination of HLA mismatching at the epitope/eplet level. Given the observation that certain HLA allele mismatches appear to be more antigenic than others, this retrospective study followed the development of DSA in pediatric transplant recipients as a consequence of donor-recipient epitope/eplet mismatches.
Method: Fifty-two pediatric renal transplant recipients (31 deceased donors, 21 living donors) transplanted between 2011- 2015 were reviewed for their development of DSA. HLA matchmaker software was used to identify and enumerate HLA epitope/eplet mismatches.
Result: Twenty six of the 52 patients, developed DSA, the majority (21/26 or 81%) being Class II DSA. Within the DSA positive group there were more DQ epitope/eplet mismatches than DR epitope/eplet mismatches (p= 0.006). There were significantly more DQ epitope mismatches in the DSA positive patients than in the DSA negative patients (p=0.008). Specific epitopes/eplets within the HLA-DQ locus of the donor (55PP, 70RT, 52PL and 140T) were more frequently mismatched in the DSA positive group compared to the DSA negative group (p<0.0001), suggesting that these may be the immunodominant epitopes/eplets associated with development of de-novo DSA.
|DQ Epitope||Frequency in DSA positive patients||Frequency in DSA negative patients|
|55PP||10/26 (38%)||1/26 (4%)|
|70RT||9/26 (34%)||1/26 (4%)|
|52PL||9/26 (34%)||2/26 (8%)|
|140T||9/26 (34%)||2/26 (8%)|
In the DSA positive group 12 out of 26 patients (46%) had >10 DQ epitope mismatches as compared to only 3 out of 26 (11.5%) in the DSA negative group.
Conclusion: Pediatric renal transplant recipients who develop DSA appear to have more donor-recipient HLA-DQ epitope/eplet mismatches than DSA negative patients. Epitope/eplet matching may be an important consideration in the future to help prevent the development of Class II DSA and may be a modifiable risk factor impacting long term pediatric graft survival.
CITATION INFORMATION: George R., Sullivan H., Garro R., Winterberg P., Warshaw B., Gebel H., Bray R. Epitope/Eplet Mismatch in Pediatric Renal Transplantation and Development of Donor Specific Antibody Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:George R, Sullivan H, Garro R, Winterberg P, Warshaw B, Gebel H, Bray R. Epitope/Eplet Mismatch in Pediatric Renal Transplantation and Development of Donor Specific Antibody [abstract]. https://atcmeetingabstracts.com/abstract/epitope-eplet-mismatch-in-pediatric-renal-transplantation-and-development-of-donor-specific-antibody/. Accessed April 10, 2020.
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