OR53 Three case reports: NGS-based high resolution HLA typing permits better assessment of donor-recipient compatibility in solid organ transplant

NGS based HLA typing is useful for the bone marrow transplantation, but its utility for solid organ transplantation (SOT) is unclear. Our lab has been using NGS based HLA typing as the primary methodology to support all transplant programs. Here, we present three cases to show the impact of this technology on SOT. Case 1: Relevance to living donor selection. A 15-year old girl required a kidney transplant due to focal segmental glomerulosclerosis. Prior to transplant, anti-HLA DQ2 antibody was detected by single antigen bead (SAB) assay with the highest MFI = 5653, specific to DQA1∗05:01, DQB1∗02:01. Both potential living donors possess DQ2. NGS based typing identified the preferred donor to avoid this dimer. The patient has been transplanted for 9 months, and is doing well without any DSAs. Case 2: Relevance to dissect the reason for lacking DSA detection. An 18-year old girl with a history of diffuse mesangial sclerosis received a living donor (father) kidney transplant in 1999. DSAs have never been detected post-transplant. The patient developed chronic allograft dysfunction, and was relisted for the second transplant. When evaluating her sibling as a potential donor, weak positive reactivity to B cells was detected in flow and cytotoxic cross matches. NGS based HLA typing showed the sibling and the father share A∗31:15 and DRB1∗04:11, which are mismatched antigens to the patient, but are not in the panel of SAB assay. If the DSAs against A∗31:15 or DRB1∗04:11 ever developed, they would not be detected. These results may explain the chronic allograft dysfunction and the positive crossmatch results in the absent of DSA detection. Case 3: Relevance to better assess antibody reactivity to closely related alleles and the risk for antibody-mediated rejection. An 18-year girl with a history of chronic kidney disease received a deceased donor kidney transplant in 2008 and a liver transplant in 2011. Beginning in 2013, DSAs to DQ9 were detected. The MFI level varied significantly among three DQ9 beads, ranging from 2000 to 12,000. Prior to NGS typing, the dimer DQA1∗03:02, DQB1∗03:03 with the highest MFI (12000) was reported. However the patient was doing well and her kidney function was stable. NGS based HLA typing identified the donor as DQA1∗02:01, DQB1∗03:03. The MFI for this dimer was 2000, which may explain the clinical observation. D. Ferriola: Other (Identify); Company/Organization; Royalties . D. Monos: Scientific/Medical Advisor; Company/Organization; Omixon .