A positive complement dependent cytotoxicity immunoglobulin G crossmatch due to auto-antibodies with a negative luminex bead assays in a renal transplant recipient: A Diagnostic dilemma

Transplant recipients are always at a risk of developing anti-human leukocyte antigen (HLA) antibodies due to prior sensitizing events such as blood transfusions, multiple pregnancies, or transplantation. Unexpected positive outcomes can be seen in complement dependent cytotoxicity (CDC) based assays due to underlying autoimmune disorders or pharmacological treatment (rituximab/intravenous immunoglobulin/anti-thymocyte globulin administration), therefore, limiting its value. CDC based assay results strongly depend on the vitality of the donor lymphocytes, highlighting another major limitation of this assay. Thus, as an alternative approach, solid phase based crossmatch assays were introduced which function independently of the cell quality and have higher sensitivity and specificity in detecting anti-HLA antibodies. We describe a case where the patient awaiting renal transplantation from living related donor was evaluated by pretransplant histocompatibility testing for the detection of anti-HLA antibodies. The histocompatibility testing revealed positive CDC anti-human globulin and flow crossmatch along with negative Luminex based assays (HLA antibody screen, luminex crossmatch, and luminex single bead assay). Detailed histocompatibility workup revealed immunoglobulin G autoantibodies which were complement activating and lympocytoxic in nature.