Alpha-Gal syndrome (AGS) is an acquired allergic reaction caused by IgE antibodies against galactose-α-1-3-galactose (alpha-Gal), a carbohydrate expressed by most mammals but not humans. Bites from certain tick species, Amblyomma americanum (lone star tick) in the U.S., can stimulate the production of these antibodies. Many alpha-Gal antibodies cross-react with the human blood group B-antigen, and allergic transfusion reactions (ATRs) have been reported in blood type O recipients receiving B or AB blood products, leading researchers to hypothesize that anti-alpha-Gal IgE-mediated ATRs may occur (termed transfusion-related alpha-Gal syndrome [TRAGS]). To test whether individuals with type O individuals receiving B or AB blood products have higher ATR risk, researchers retrospectively analyzed over 500,000 platelet and plasma transfusions (0.3% ATR rate) at 40 sites in five countries where rates of AGS had been calculated in 2024. In the nine U.S. sites categorized with high AGS (11 to 87 AGS cases/million population/year), more ATRs occurred in type O recipients who received B or AB platelets or plasma compared with type O recipients who received type O platelets or plasma (overall risk ratio, 3.93; 95% C.I., 2.96 to 5.21; p <0.001). No difference in ATR risk was observed between type O recipients who received B or AB products vs. those who received type O products in areas with fewer cases of AGS (0 to <11 AGS cases/million/population/year). These data suggest TRAGS could be occurring. No evidence of TRAGS was observed outside of the U.S. More research is needed to better understand the association between anti-alpha-Gal IgE and TRAGS and whether individuals with group A blood are affected.
References:
- Kaufman RM, Hoen AG, Khan J, Knudson CM, et al. Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome. JAMA Intern Med. 2026 Aug 24:e263983. doi: 10.1001/jamainternmed.2026.3983. Epub ahead of print. PMID: 42636004; PMCID: PMC13504484.
- Hollenhorst MA, Anderson JR, Dzik W. Ticks and Transfusion at the Crossroads—Alpha-Gal Syndrome. JAMA Intern Med. Published online August 24, 2026. doi:10.1001/jamainternmed.2026.3993
