P046 HLA class II eplet mismatch predicts de novo DSA formation at 3 and 12 months post lung transplant

• Published in: Human immunology 2017-09, Vol.78, p.88-88
• Main Authors: Walton, Duncan, Hiho, Steven, Cantwell, Linda, Ta, Joseph, Loskot, Monika, Phan, Tracy, Levvey, Bronwyn, Snell, Greg, Paraskeva, Miranda, Westall, Glen
• Format: Article
• Language: English
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2017.06.106

The aims of this prospective study were: 1) investigate a cohort of LTx recipients for the presence and clinical associations anti-HLA antibodies 2) Examine association between HLA eplet mismatch and HLA de novo antibody formation. From Jul 2014-Aug 2015, 49 patients were enrolled at time of listing for LTx, and blood samples obtained pre-transplant and at 3 and 12months post-LTx. Samples were HLA typed (SSO, One Lambda Inc.) then screened for antibodies by single antigen beads for HLA, including C1q (One Lambda Inc.), HLA compatibility was assessed using HLAMatchmaker (version 2.1) and de novo donor specific antibodies (DSA) were determined using a MFI cut off >500. HLA antibodies were detected pre-transplant in 21/49 patients (43%); 7 with Class I, 2 with Class II and 12 with both Class I&II, and four patients having pre-transplant DSA. 13/49 (27%) developed de novo HLA DSAs by 3months post LTx; 1 with Class I, 8 with Class II, 4 with Class I&II. At 12months post-transplant 5/49 patients had de novo class II DSA, with all having eplet scores greater than 40 for class II. When DSA development was correlated with eplet mismatch no significance was observed at Class I, however DRB1∗/DQA&B eplet mismatches correlated to HLA Class II DSA formation when using a cut-off of ⩾40, at 3months (p=0.008) and at 12months (p=0.02). The C1q assay was positive for 5/12 de novo class II samples at 3months post-transplant and 1/5 at 12month all showing HLA-DQ specificities. There was no association with HLA antibody levels and the early measures of LTx outcomes, ICU and hospital days or acute rejection rates at 3months post LTx. Having previously shown that high class II eplet mismatches is associated with RAS, we now show that the same factors are associated with de novo HLA class II DSA early post-Tx and that these levels are dynamic over time. We postulate that the RAS phenotype of CLAD may represent chronic AMR. G. Westall:1. Grant/Research Support; Company/Organization; One Lambda.