A New Trial to Measure ABO Antibodies Using Complement-Dependent Cytotoxicity

Area of Science:

• Transplantation immunology
• Serology
• Clinical chemistry

Background:

• ABO antibody (Ab) titration is crucial for monitoring ABO-incompatible (ABOi) solid organ transplantation (SOT).
• Existing ABO Ab tests primarily detect Ab binding, not necessarily in vivo activity.
• Complement-dependent cytotoxicity (CDC) offers a potential alternative for measuring ABO Ab levels.

Purpose of the Study:

• To evaluate the utility of complement-dependent cytotoxicity (CDC) for measuring ABO antibody (Ab) levels.
• To compare CDC-derived hemolysis with traditional ABO Ab titers in ABOi SOT patients.
• To investigate the role of immunoglobulin M (IgM) and immunoglobulin G (IgG) in ABO Ab activity.

Main Methods:

• Studied 93 serum samples from patients undergoing ABOi SOT.
• Incubated patient sera with A1 or B cells and human complement.
• Measured free hemoglobin (Hb) via spectrophotometry to determine hemolysis (%) and compared with ABO Ab titers.

Main Results:

• A mild correlation was observed between hemolysis and ABO Ab titers (correlation coefficients 0.3660–0.4968, p < 0.0001).
• Multiple linear regression indicated higher anti-A and anti-B hemolysis with IgM compared to IgG.
• Significant variation in hemolysis was noted within identical Ab titers, suggesting limitations of current titration methods.

Conclusions:

• Complement-dependent cytotoxicity (CDC) shows promise as a novel method for ABO Ab measurement.
• Immunoglobulin M (IgM) appears to play a more significant role in in vivo ABO Ab activity than immunoglobulin G (IgG).
• This study supports the development of CDC-based ABO Ab titration assays to inform SOT treatment policies.