Detection and Quantification of Polymorphic <scp>MICA</scp> and <scp>MICB</scp> Molecules in Immunoassays: Initial Insights

The MICA and MICB molecules, expressed on the cell membrane in response to cellular stress or cancer transformation, pose significant challenges for immunoassays. They exhibit high sequence and structural similarity, alongside considerable allelic polymorphism, with 291 and 53 known protein sequences, respectively. Some researchers treat MICA and MICB as a unified target because of their structural and functional similarities, while others distinguish between them. However, which approach is superior and under what circumstances remains unknown. Moreover, information about assays' reactivity with MICA and MICB allelic variants is often missing. In this study, we developed 10 monoclonal antibodies (mAbs) and two sandwich ELISAs for the detection and quantification of these molecules. We assembled a panel of recombinant proteins representing the diversity of MICA and MICB in the European population and profiled the reactivities of the mAbs and ELISAs. The performance of these sandwich ELISAs was evaluated using samples from prostate cancer patients and pregnant women experiencing premature rupture of membranes. Our study assessed the impact of MICA and MICB polymorphism on their detection and quantification by immunological methods, providing evidence to support differential or non-differential approaches for their detection.