Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome
JAMA Intern Med. 2026 Aug 24:e263983.
doi: 10.1001/jamainternmed.2026.3983. Online ahead of print.
Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome
Richard M Kaufman 1, Anne G Hoen 2, Jenna Khan 3, C Michael Knudson 4, Ryan A Metcalf 5, Andres E Mindiola Romero 6, Allison Mo 7, Richard Schäfer 8, Minoko Takanashi 9, Nancy M Dunbar 1; UPTICK Study Group; for the Biomedical Excellence for Safer Transfusion (BEST) Collaborative; Richard M Kaufman 1, Anne G Hoen 2, Jenna Khan 3, C Michael Knudson 4, Ryan A Metcalf 5, Andres E Mindiola Romero 6, Allison Mo 7, Richard Schäfer 8, Minoko Takanashi 9, Sajjad Afraz 10, Elizabeth S Allen 11, Jennifer Andrews 12, Konstanze Aurich 13, John Casey 14, Claudia S Cohn 15, Jensyn K Cone Sullivan 16, Clara C Cousins 17, Elizabeth P Crowe 18, Valeria De Giorgi 19, Meghan Delaney 20, Regina M DelBaugh 21, Colleen W Gilstad 22, Alexander Gofton 23, Jeanne E Hendrickson 24, Kate Hill 25, Keenan O Hogan 26, Catherine Humbrecht 27, Kazuhiko Ikeda 28, Cyril Jacquot 20, Ayda Javanbakht 29, Justin E Juskewitch 30, Wen Lu 30, Monique M Menzies Wojtowicz 31, Maureen J Miller 19, Georgia Mills 31, Anna C Nelson 32, Monica B Pagano 33, Marie C Pauly 8, Jessica L Poisson 34, Jay S Raval 35, Nabiha H Saifee 36, Nikitha Samy 29, Tomohiko Sato 37, Yoshinori Takeda 22, Suzanne R Thibodeaux 38, Pierre Tiberghien 39, Sheryl van Nunen 31, Mrigender S Virk 10, Kamille West-Mitchell 19, Erica M Wood 7, Jun Yamanouchi 40, Satoshi Yoshihara 41, X Long Zheng 26, Alyssa Ziman 17, Nancy M Dunbar 1
Collaborators, Affiliations Expand
PMID: 42636004
PMCID: PMC13504484 (available on 2027-08-24)
Abstract
Importance: Recent case reports suggest that B antigen-containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose-α-1,3-galactose (alpha-gal).
Objective: To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O.
Design, setting, and participants: In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included.
Exposures: Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared.
Main outcomes and measures: Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters.
Results: In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected.
Conclusions and relevance: This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Metcalf reported receiving grants from Werfen, Haemonetics, Hemosonics, and Octapharma and personal fees from Werfen, Cerus, and UpToDate outside the submitted work and codeveloping a data visualization tool that has been disclosed as an invention but is not currently commercialized. Dr Cohn reported receiving personal fees from the Association for the Advancement of Blood and Biotherapies during the conduct of the study. Dr Crowe reported receiving personal fees from Terumo BCT and Plas Free, Ltd outside the submitted work. Dr Delaney reported receiving personal fees from Grifols outside the submitted work. Dr Ikeda reported receiving grants from Hokuyo Denki, Kyokuto Pharmaceutical Industrial Co, Ltd and personal fees from GSK, JB, Nippon Shinyaku, Novartis, PharmaEssentia, Recordati Rare Diseases, Takeda, Kyowa-Kirin, Kissei, and Zeria outside the submitted work. Dr Menzies Wojtowicz reported receiving honoraria from BeOne, Eli Lilly, and Johnson & Johnson; personal fees from AstraZeneca, AbbVie, and Eli Lilly; and research funding from AbbVie; and receiving personal fees from AstraZeneca, Eli Lilly, and Johnson & Johnson outside the submitted work. Dr Poisson reported receiving personal fees from Cerus outside the submitted work. Dr Sato reported receiving research funding from the Japanese Red Cross and grants from the Japan Society for the Promotion of Science outside the submitted work. Dr Thibodeaux reported receiving personal fees from the University of Nebraska and TerumoBCT outside the submitted work and serving on the Board of Directors for the Association for the Advancement of Blood and Biotherapies. Dr Zheng reported serving on the Takeda Advisory Board and Sanofi Advisory Board, receiving nonfinancial support from The Blood Project Board of Trustees and a grant to the University of Kansas Medical Center from Lee's Pharmaceuticals Research Collaboration and cofounding Clotsolution outside the submitted work. Dr Dunbar reported receiving personal fees from Grifols outside the submitted work. No other disclosures were reported.