Misidentification of preformed anti-HLA-DP antibodies leads to antibody-mediated kidney transplant rejection: a case report

Abstract

Background Patients who are HLA-sensitized are at high risk for early antibody-mediated rejection (AMR) and worse outcomes. Therefore, it is crucial to detect the presence of donor-specific antibodies (DSAs) using pretransplant antibody identification and crossmatch assays. An error in antibody identification can lead to disastrous clinical outcomes. We present a case of acute AMR associated with preformed HLA-DPα and HLA-DPβ DSAs that were not identified before transplantation. Case presentation A 27-year-old woman received a second kidney transplant from a deceased donor. Her pretransplant panel-reactive antibody level was 94%. The complement-dependent cytotoxicity crossmatch was negative for T and B cells at the time of transplantation. She experienced early acute AMR proven by a kidney biopsy. Single antigen bead testing of the patient’s serum at the time of rejection as well as the pre-second transplant serum revealed strong antibodies against the DPA1*01:03 and DPB1*02:01 alleles in the second donor. These antibodies were not identified by phenotypic bead assay during the patient’s time on the waiting list. The patient was treated with plasmapheresis and anti-thymocyte globulin. However, she experienced abdominal pain on day 37 post-transplantation. Surgical exploration revealed a laceration on the transplanted kidney, which was then repaired. Subsequently, infected hematoma was suspected and the transplanted kidney was removed. Conclusion The present case highlights the clinical significance of preformed HLA-DPα and HLA-DPβ DSAs. Accuracy in determination of HLA antibodies before transplantattion is critical for transplant outcome. HLA-DP typing and single antigen bead testing are recommended for a precise antibody interpretation, especially in highly sensitized patients. Careful interpretation of antibody testing results is essential for the success of organ transplantation.

Unrepresented human leucocyte antigen alleles in single‐antigen bead assays: A single‐centre cohort study

“…eplet or ‘epitope’ analysis) (Nishikawa et al., 2023). However, the awareness for the need to perform such analyses may not be universal (Nishikawa et al., 2023; Schlaf et al., 2021; Thammanichanond et al., 2022). There is currently no accepted standardized method to perform eplet analysis and the expertise to perform such analyses may not be uniform across different HLA laboratories and clinical transplant teams (Nishikawa et al., 2023; Schlaf et al., 2021; Thammanichanond et al., 2022).…”

“…SAB assays will not be able to detect allele‐specific DSAs if their corresponding HLA alleles are unrepresented. Cases with AMR or positive cell‐based crossmatches but negative DSAs on SAB assays may also be explained by undetectable DSAs from unrepresented HLA alleles (Nishikawa et al., 2023; Rodriguez‐Ramirez et al., 2022; Schlaf et al., 2021; Thammanichanond et al., 2022).…”