Ticks and transfusions: a potentially fatal mix!
Connected Content This is a commentary to: Severe allergic transfusion reactions to group B/AB plasma or platelets in group O recipients are linked to α-Gal sensitization
Luc de Chaisemartin, Virginie de la Taille, Pascale Nicaise-Roland, Lucile Malard, Cléo Beuscart, Aurélie Gouel-Chéron, Syria Laperche, Pierre Tiberghien
Blood (2026) 147 (25): 3113–3117
In this issue of Blood, de Chaisemartin et al1 describe their search for galactose-α-1,3-galactose (α-Gal)–specific immunoglobulin E (IgE) in a cohort of 59 patients with severe allergic transfusion reactions (ATRs), where they found that group O recipients of group B or AB plasma or platelet concentrates are substantially more likely to exhibit high titers of group B cross-reactive anti–α-Gal IgE than other patients, strongly implicating a causative role for α-Gal sensitization in these severe ATRs. Their findings support the hypothesis that α-Gal sensitization, usually because of exposure to the glycan from a tick bite, is an additional mechanism responsible for ATRs in major ABO-incompatible transfusion reactions. This work follows on their earlier publication reporting their nationwide hemovigilance retrospective observational study in France,2 where they reported that group O recipients of group B or AB platelet concentrates or plasma were at significantly higher risk of severe ATRs compared with recipients of other ABO combinations.2
A 21st-century pandemic of noncommunicable disease (tick bite–induced sensitization to the glycan α-Gal3) has grown from being observed after the bite from 1 tick species, in 1 country, and on 1 continent when first described in 2007,4 to being triggered by several tick species, in 50 countries, and on all 6 continents where humans are bitten by ticks (as of March 2026). Termed mammalian meat allergy after a tick bite, it is also known as α-Gal syndrome (AGS). This condition presents management challenges in many fields of medicine (eg, oncology, emergency medicine, cardiology, and cardiothoracic surgery) and especially in transfusion medicine.
Crucially, only a few of those individuals who develop specific IgE to α-Gal (50% after 2 tick bites)5 demonstrate clinical reactivity to mammalian meat.6 In the high- risk population of hunters and forest service workers with their intensive exposure to tick bites, studied by Fischer et al,6 the prevalence of α-Gal-sIgE–positive (≥0.10 kUA/L) individuals was 35.0%, whereas the prevalence of individuals with α-Gal-sIgE levels >0.35 kUA/L was 19.3%. α-Gal-sIgE positivity was associated with recent tick bites. Mammalian meat-induced delayed anaphylaxis was found in 8.6% of the participants with α-Gal-sIgE levels ≥0.35 kUA/L. This translates to up to 35% of the population living in areas where ticks are very highly endemic being at risk of potentially life-threatening anaphylaxis to other sources of α-Gal, with the vast majority having no clinical history of symptoms following ingestion of mammalian meat6 and some not recalling having had a tick bite. Importantly, when the α-Gal exposure is IV, then the risk of a more severe allergic reaction is increased, as seen in allergic reactions to cetuximab.7
Notably, although fatal anaphylaxis to mammalian meat is reported rarely (only 3 documented cases worldwide: 2015 [Scotland], 2022 [Australia], and 2024 [United States]), almost 5 times (4.7 times) that number of patients have perished from AGS after treatment (often the first dose) with cetuximab, which is produced in mouse-derived cell lines that express the α-Gal sugar (13 fatalities reported from Europe,7 Japan,8 and Australia) with 1 fatal severe allergic transfusion reaction reported from the United States.9
To date, 5 group O patients who have experienced severe ATRs following transfusion with group B plasma or platelets have been reported. In 4 of these patients, IgE specific to α-Gal was demonstrable (1 patient was not tested). One of these reactions had a fatal outcome.9 The proposed mechanism for these reactions is the antigenic similarity between the group B determinant and the α-Gal epitope.9 If a non–B blood group patient has developed specific IgE directed against α-Gal after a tick bite, then they may develop an allergic reaction to the B group determinant in blood components.
de Chaisemartin et al divided 59 patients with a severe ATR into 3 groups: group 1 (n = 12), group O recipients who received group B or AB plasma or platelets; group 2 (n = 4), group O recipients who received group A plasma or platelets; and group 3 (n = 43), all remaining patients. Of the group 1 patients, 66.7% (8/12) were positive for anti–α-Gal IgE compared to 0% (0/4) group 2 and 7% (3/43) group 3 patients (all group O recipients of group O products). Titers of anti–α-Gal IgE were significantly higher in patients in group 1 (O having received a group B or AB product) compared to group 2 and group 3 (P = .0072 and P< .0001, respectively). To verify that α-Gal–specific IgE could indeed bind B group erythrocytes, IgE inhibition assays were performed. Only incubation with group B red blood cell (RBC) led to a significant reduction in α-Gal–specific IgE titers compared to incubation with group O (P = .009), and IgE binding was detected by flow cytometry on the surface of group B RBCs but not group O RBCs (P = .03). Based on these findings, de Chaisemartin et al concluded that the possibility of α-Gal sensitization should be investigated in all group O recipients after a severe ATR involving group B/AB blood components.
Clearly, the next step would be to extend this study worldwide to confirm that this risk is present in patients who received transfusions in other regions where ticks are endemic and whether ATRs occur if transfusion practices differ in offering B group plasma or platelets to group O patients. If this risk is confirmed, transfusion practices should be modified in these regions (by checking for α-Gal–specific IgE before transfusion of B/AB platelets or plasma where possible or avoiding their use, if possible, where the patient’s status is unknown) and then observing prospectively whether such measures abolish the risk of severe and potentially fatal anaphylaxis to B/AB platelets or plasma in non–group B patients. A similar approach to reducing severe anaphylaxis to cetuximab has been shown to be successful.10
Conflict-of-interest disclosure: The author declares no competing financial interests.