P200 High-resolution HLA typing of deceased donors enables accurate identification of allle_specific DSA

Abstract

HLA typing of donors for solid organ transplantation is performed with the primary goal of avoiding hyperacute antibody-mediated rejection (AMR) caused by recipient antibodies against donor antigens. Given the need for rapid testing of deceased donors, SSP or SSO methods are used to enable timely HLA typing at the serologic split antigen level. However, these methods do not provide unambiguous allele-level genotyping. This ambiguity can be problematic in patients with allele-specific anti-HLA antibodies. We report a case of suspected AMR following deceased donor kidney transplantation as an example of high-resolution HLA genotyping enabling identification of donor-specific antibodies (DSA). The patient was transplanted in 2010 with a flow cytometric crossmatch negative deceased donor kidney. History was remarkable for biopsy-proven C4d positive acute AMR in 2012 successfully treated by IVIG and rituximab. In late 2016, the patient developed increased proteinuria. Biopsy demonstrated changes consistent with both active and chronic AMR, but without presence of C4d. Solid-phase anti-HLA antibody testing did not demonstrate identifiable DSA, though there was evidence of allele-specific antibodies (Table 1). To investigate whether these represented DSA, donor DNA was re-typed for HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1,and -DPB1 by next-generation DNA sequencing (NGS). High-resolution HLA typing identified DSA against DQA1∗05:05 and DRB3∗03:01. Reactivity against DR52 or DQA05 would not have been called based upon average group reactivity. Identification of DSA supported diagnosis of AMR and enabled tracking of DSA as an objective measure of the efficacy of therapy. The increasing frequency of allele-specific DSA has led us to implement routine re-testing of solid organ donors for high-resolution HLA typing to promote accurate and efficient evaluation of potential allele-specific DSA. Download : Download high-res image (123KB) Download : Download full-size image