The shared epitope phenomenon-A potential impediment to virtual crossmatch accuracy

Area of Science:

• Immunology
• Transplantation
• Medical Diagnostics

Background:

• The implementation of the new kidney allocation system (KAS) increases reliance on virtual crossmatch (vXM) for assessing HLA antibodies.
• Accurate vXM depends on precise recipient antibody profiling and donor HLA typing.
• Single antigen bead (SAB) assays improve HLA antibody detection but have limitations for sensitized patients.

Purpose of the Study:

• To explain the shared-epitope phenomenon affecting HLA antibody detection.
• To illustrate how this phenomenon can lead to underrepresentation of antibody strength.
• To present case studies for improved histocompatibility consultation.

Main Methods:

• Focus on the shared-epitope phenomenon in SAB assays.
• Analysis of antibody binding to competing targets on multiple antigens.
• Case study investigations of complex antibody profiles.

Main Results:

• The shared-epitope phenomenon can dilute Mean Fluorescence Intensity (MFI) readouts.
• This can lead to underestimation or missed detection of clinically significant HLA antibodies.
• Case studies demonstrate methods to identify and interpret these complex antibody profiles.

Conclusions:

• Accurate histocompatibility assessment requires understanding the shared-epitope phenomenon.
• Investigating diluted MFI signals is crucial for sensitized patients.
• Improved interpretation leads to more accurate vXM and better kidney allocation decisions.