Clinical implications of imlifidase interference in antibody screening and transfusion management

Imlifidase has received conditional approval from the EMA for desensitizing deceased donor kidney transplant recipients. It works by cleaving IgG into F(ab')² and Fc fragments, thereby reducing the risk of antibody-mediated rejection. However, its impact on diagnostic assays remains understudied.

We present the case of a 55-year-old male who underwent desensitization for an HLA-incompatible deceased-donor kidney transplantation. The patient had a documented history of clinically relevant alloantibodies against erythrocyte antigens. Specifically, anti-K alloantibodies were identified by pre-treatment alloantibody screening prior to the initiation of imlifidase therapy. Following imlifidase treatment, alloantibody screening prior to blood transfusion returned a false-negative result, likely due to the elimination of IgG alloantibodies by imlifidase. Despite the elimination of detectable alloantibodies, transfusion management was guided by the patient's documented antibody history from a national registry, ensuring the administration of antigen-compatible blood transfusions.

To our knowledge, this represents the first documented case demonstrating that imlifidase treatment may interfere with alloantibody screening in routine blood transfusion diagnostics. False-negative results may mask clinically relevant alloantibodies, thereby increasing the risk of incompatible transfusions and delayed hemolytic reactions. This highlights the need for caution when interpreting alloantibody screening results in imlifidase-treated patients and calls for future guidelines or recommendations to manage potential interference, minimizing risks and ensuring patient safety in blood transfusions.