Very low residual concentrations of rituximab long after infusion still induce positive B-cell complement-dependent cytotoxicity-crossmatch

Abstract

Rituximab may induce positive B-cell complement-dependent cytotoxicity crossmatch (CDC-XM) in the absence of donor-specific antibodies, as we report in these two cases. We retrospectively assessed the in vitro concentration-effect relationship of rituximab in sera. B-cell CDC-XM results were positive only in the presence of rituximab, even with low concentrations (inferior to 1 μg/mL). Moreover, rituximab neutralization with increasing concentration of an anti-rituximab-idiotype monoclonal antibody progressively reduced B-cell lysis. In conclusion, measurement of rituximab content may be useful to identify sera at risk of misinterpretation in immunized patients.

Keywords: CDC; DSA; HLA; IvIg; SA; XM; complement-dependent cytotoxicity; crossmatch; donor-specific antibodies; human leucocyte antigen; intravenous immunoglobulin; single antigen.