Establishing "Glycoantigens" as a cross-field concept in Glycobiology, transfusion, transplant, and immunology.

Cell-surface glycans (carbohydrate structures) serve as critical antigens in transfusion and transplantation, yet their study remains fragmented across disciplines. The ABO blood group system, the most clinically tested glycan compatibility system, is still assessed using the same broad phenotypic classifications (A, B, AB, O) established over 125 years ago, which fail to capture the underlying structural diversity of glycans or account for tissue-specific expression patterns. Beyond ABO, numerous other glycoantigens remain almost entirely neglected in clinical compatibility testing, despite their potential relevance in antibody-mediated rejection, xenotransplantation, and unexplained graft complications. I propose establishing "glycoantigens" as a unified cross-disciplinary concept encompassing immunogenic glycan epitopes relevant to compatibility in transfusion and transplantation. Modern tools, including next-generation and nanopore sequencing of glycosyltransferase genes, glycan microarrays, Luminex-based bead immunoassays, and advanced mass spectrometry, now enable systematic characterization of these complex structures. I outline a tiered clinical implementation pathway, propose an integrated glycoantigen database linking genomic, structural, expression, and serologic data, and describe a Glycoantigen Prediction Pipeline that translates multi-gene genotypes through predicted enzyme activities into tissue-specific glycoantigen profiles with antibody risk estimates. Recognizing glycoantigens as a distinct research area would foster collaboration between glycobiologists and transplant immunologists, enable therapeutic innovations, and potentially explain cases of graft rejection not attributable to HLA or other known factors. Although the initial focus is transfusion and transplantation, anti-glycan antibodies are clinically significant across allergy, neurology, gastroenterology, infectious disease, and oncology, and the proposed database could ultimately serve as a broader resource for glycoantigen biology in medicine.