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

Area of Science:

• Immunology
• Transplantation Immunology
• Clinical Chemistry

Background:

• Complement-dependent cytotoxicity crossmatch (CDC-XM) is crucial for assessing antibody-mediated rejection risk in transplantation.
• Rituximab, a chimeric monoclonal antibody, targets CD20-expressing B cells and can interfere with immunological assays.
• False positive CDC-XM results can lead to unnecessary treatment or delayed transplantation.

Observation:

• Two cases are presented where rituximab induced positive B-cell CDC-XM in the absence of donor-specific antibodies.
• In vitro analysis demonstrated a concentration-effect relationship between rituximab and B-cell lysis.
• Positive B-cell CDC-XM results were observed even with rituximab concentrations below 1 μg/mL.

Findings:

• Rituximab directly mediates B-cell lysis in a dose-dependent manner, independent of donor-specific antibodies.
• Neutralization of rituximab with an anti-idiotype antibody reduced B-cell lysis, confirming rituximab's role.
• The presence of rituximab is the causative factor for false positive CDC-XM results.

Implications:

• Accurate interpretation of CDC-XM requires consideration of rituximab therapy in patients.
• Measurement of rituximab levels in patient sera may be necessary to avoid misinterpretation of crossmatch results.
• This finding has significant implications for pre-transplant risk assessment and management strategies in patients treated with rituximab.