Early antibody-mediated rejection caused by a preexisting anti-HLA-DP5 donor-specific antibody not included in routine pretransplant screening: a case report and review of the literature

Abstract Background Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are a major cause of antibody-mediated rejection (AMR) after kidney transplantation. Routine pretransplant screening usually focuses on HLA typing and antibodies against HLA-A, -B, -C, -DRB1, and -DQB1. HLA-DPB1 typing is not always included because HLA-DPB1 antigens are expressed at relatively low levels and have historically been considered less immunogenic. However, emerging evidence suggests that anti-HLA-DPB1 antibodies may be sometimes clinically significant. Case presentation A 35-year-old woman with end-stage kidney disease caused by glycogen storage disease type II underwent ABO-compatible(O → A) living kidney transplantation from her mother. Pretransplant immunological evaluation revealed negative complement-dependent cytotoxicity and flow cytometric crossmatch results, and no DSA against HLA-A, -B, -C, -DRB1, or -DQB1 were detected. On postoperative day 2, the patient developed acute pancreatitis. Therapeutic drug monitoring showed trough levels of tacrolimus of 3.5 ng/mL and mycophenolate mofetil of 0.8 μg/mL. Although these levels were within the therapeutic range, drug-induced pancreatitis was suspected on the basis of the clinical course. On postoperative day 4, the patient developed anuria and Doppler ultrasonography demonstrated loss of diastolic blood flow in the transplanted kidney. Despite aggressive fluid resuscitation, graft perfusion did not improve. Graft biopsy could not be performed because cellulitis around the graft region and thrombocytopenia increased the risk of complications. HLA-DPB1 typing and DSA re-evaluation revealed a DSA against HLA-DPw5 (DPB1 * 05:01) with a normalized mean fluorescence intensity (nMFI) of 10,562. Retrospective analysis of the stored pretransplant serum sample revealed the same antibody with an nMFI of 2,792. Treatment with plasmapheresis and rituximab was initiated, and graft function gradually recovered to creatinine 1.0 mg/dL after approximately 3 weeks of anuria. Conclusions This case suggests that anti-HLA-DP antibodies may be sometimes clinically relevant and could be considered in selected cases, particularly those with a history of pregnancy, blood transfusions or previous transplants, or in cases where unexplained early graft dysfunction is observed.