Antigen and eplet coverage by representative solid-phase immunoassays for anti-HLA antibody screen

Area of Science:

• Immunology
• Transplantation Science
• Clinical Chemistry

Background:

• Solid-phase immunoassays (SPIs) are essential for detecting anti-human leukocyte antigen (HLA) antibodies in transplantation.
• Comprehensive antigen and eplet coverage across different SPI configurations remains underexplored.

Purpose of the Study:

• To systematically compare the antigen and eplet coverage of four commercial SPI panels: Mixed, Panel Reactive Antibody (PRA), Single Antigen Bead (SAB), and ExPlex.
• To assess the representation of eplets from the HLA Eplet Registry within these assays.

Main Methods:

• Comparison of four commercial SPI panels against the HLA Eplet Registry.
• Analysis of antigen and eplet representation, including exclusive and shared eplets.
• Examination of the correlation between eplet dose and antibody reactivity in the PRA assay.

Main Results:

• High coverage of HLA eplets was observed: 99.6% of Class I and 100% of Class II eplets were covered by at least one assay.
• 209 Class I (82.9%) and 189 Class II (72.7%) eplets were covered by all four assays.
• Two Class II eplets were exclusive to the SAB assay; ExPlex expanded eplet diversity within antigenic contexts.

Conclusions:

• Current SPIs provide broad coverage of HLA eplets, offering acceptable antigenic coverage for pre-transplant immune risk screening.
• Variability in eplet representation exists, emphasizing the importance of assay selection.
• An R script is provided for ongoing analysis and monitoring of HLA antigen and eplet coverage.