Severe allergic transfusion reactions to B/AB plasma or platelets in group O recipients are linked to α‑Gal sensitization

Allergic transfusion reactions (ATR) are potentially lethal adverse events that occur in approximately 0.3%-6% of plasma or platelet transfusions. The main mechanism described is an IgE-mediated response to donor proteins, such as IgA and haptoglobin in deficient patients. Recently, in a nationwide retrospective observational study, we reported that group O recipients of group B or AB platelet concentrates or plasma were at significantly higher risk of severe ATR than recipients with other ABO combinations. Given the antigenic proximity between group B determinant and the galactose-α-1,3-galactose (α-Gal) epitope, we hypothesize a role for α-gal IgE-mediated sensitization in these ATRs. In this report, we investigated the presence of anti- α-Gal IgE in a cohort of 59 patients with severe ATR. We found that group O recipients of group B or AB blood components (plasma or platelet concentrates) were substantially more likely to exhibit high titers of group B cross-reactive anti-α-gal IgE than other patients, supporting our hypothesis that α-gal sensitization underlies these severe ATRs. These findings suggest that α-gal sensitization is an additional mechanism responsible for ATRs in major ABO-incompatible transfusion and should be systematically explored in group O patients having received group B/AB plasma or platelets.