Background: Therapeutic antibodies used to desensitize patients awaiting a human leukocyte antigen (HLA) or ABO-mismatched graft are suspected to interfere with the lymphocytotoxicity crossmatch (LCT-XM) test when they are present in the tested sera because of their potential ability to activate or inhibit the complement.

Methods: The most frequent therapeutic antibodies (Abs) used in desensitization protocols (intravenous immunoglobulin, rituximab, basiliximab, eculizumab, antithymocyte globulin) were added to a negative- or a positive-control serum at various concentrations, and tested in vitro in a LCT-XM test.

Results: Rituximab turned the LCT-XM positive on B cells at 0.2 ¯o;g/mL and antithymocyte globulin turned the LCT-XM positive with T and B cells at 20 ¯o;g/mL and 200 ¯o;g/mL, respectively. Treatment with dithiothreitol sera, supplemented with rituximab (0.2 and 2 ¯o;g/mL) and antithymocyte globulins (20 and 200 ¯o;g/mL), partially or totally reduced this positive interference. Intravenous immunoglobulin, eculizumab, and basiliximab did not trigger any interference with the negative control serum. In a positive LCT-XM, eculizumab did not annihilate activation of the rabbit complement, and intravenous immunoglobulin did not interfere with the HLA antibody-mediated cytotoxicity.

Conclusion: Because eculizumab within the serum did not annihilate rabbit complement activation and intravenous immunoglobulin, and basiliximab did not interfere with the crossmatch reaction, treatments based on rituximab and antithymocyte globulin need to be taken into account when interpreting a positive crossmatch test.

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