Immunological Complexity of Anti-human Leukocyte Antigen-C Donor-specific Antibodies: Therapeutic Insights from Two Cases.

Anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) are associated with antibody-mediated rejection and chronic allograft nephropathy in kidney transplantation. The interpretation of immunological assays for DSAs can be challenging due to discordant results. In this report, we present two cases of kidney transplantation involving patients with anti-HLA-C DSAs. We discuss the interpretation of their immunological tests, including complement-dependent cytotoxicity (CDC) crossmatches, flow cytometry crossmatches, and donor-specific antigen using single-antigen bead (SAB) assays, which influenced therapeutic decisions. In the first case, the patient exhibited isolated B-cell-positive crossmatch and autoantibodies, prompting the consideration of polyclonal autoantibodies in the context of underlying hepatitis C infection. The SAB assay detected only one DSA against HLA-C 03:03:01 (mean fluorescence intensity - 27,127). After careful evaluation and confirmation of negative CDC crossmatch, transplantation proceeded, and the patient demonstrated good graft function. In the second case, the patient showed a positive T-cell crossmatch along with anti-Class I HLA DSAs against HLA C*07:01 and HLA C*07:02. Despite these findings, transplantation was performed based on the absence of complement-binding antibodies. The patient experienced good graft recovery with stable kidney function. The presence of HLA-C DSAs poses challenges in transplantation decision-making. Despite conflicting studies, the pathological nature of these antibodies has been demonstrated. Careful interpretation of immunological tests and consideration of the overall clinical context are essential in making therapeutic decisions. Further research is needed to understand the clinical significance of HLA-C DSAs and their impact on graft outcomes. [ABSTRACT FROM AUTHOR]