Jacobs JW, Kaufman RM, Schwartz JY, Hall E, Tahiri T, et al.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons •
Alpha-gal syndrome (AGS) is an IgE-mediated hypersensitivity to the oligosaccharide galactose-α-1,3-galactose, acquired through tick bites and increasingly recognized as a cause of allergic reactions to mammalian-derived medical products. Every major transplant modality creates distinct conditions under which sensitized patients may encounter alpha-gal, yet AGS knowledge has developed almost entirely outside the transplant literature. In conventional solid organ transplantation, risk arises primarily from perioperative exposures to porcine-derived heparin, gelatin-based hemostatic agents, and other mammalian-derived materials. In xenotransplantation, the well-characterized role of alpha-gal as the principal xenoantigen has driven development of glycoprotein alpha-galactosyltransferase 1-knockout swine, but the distinct IgE-mediated pathway that defines AGS has received little attention. Hematopoietic stem cell transplantation introduces questions about conditioning-related immune remodeling of preexisting IgE sensitization, rabbit antithymocyte globulin as an underrecognized alpha-gal exposure, and transfusion-related alpha-gal syndrome when group B or AB plasma-containing blood products are transfused to susceptible patients. Cellular therapy manufacturing workflows that use animal-derived ancillary materials represent a further theoretical exposure pathway. Importantly, detectable anti-alpha-gal IgE does not invariably predict clinical reactivity, and the most appropriate clinical approach is risk stratification rather than reflexive exclusion. Generating the evidence base to support such stratification will require collaboration across allergy, transplant, and transfusion medicine.
Alpha-gal syndrome (AGS) is caused by IgE antibodies against the alpha-gal oligosaccharide, which is structurally similar to the Group B antigen. Recent case reports of severe allergic transfusion reactions (ATRs) in Group O patients receiving Group B plasma and platelets raise the possibility of a new adverse event, herein called transfusion-related AGS (TRAGS). The primary goal of this study was to assess the frequency of Groups B and AB plasma and platelet transfusions to Group O patients. In this multi-site retrospective study, participating sites submitted the numbers of platelet and plasma transfusions administered during a 2-year period categorized by patient and product ABO group. Fourteen sites from 10 countries participated. Group O patients received Group AB for an average of 9.9% (range 2.8%-29.2%) of plasma transfusions and Group B for 3.2% (0%-12.8%). AB plasma transfusion to Group O patients represented 4.5% (0.9%-14.6%) of the total plasma transfused; Group B 1.4% (0%-5.1%). Group O patients received Group AB for an average of 1.5% (range 0%-5.9%) of platelet transfusions and Group B for 4.1% (0%-14.2%). AB platelet transfusion to Group O patients represented 0.6% (0%-2.7%) of the total platelets transfused; Group B platelets were 1.8% (0%-6.7%). Evidence supporting the possibility of a new adverse event, TRAGS, is accumulating. This study quantifies how often Group O patients may be exposed to Group B antigen in Group B or AB plasma and/or platelet transfusions, providing an estimate of the scope of potential risk for TRAGS.
Jones VM, Nakahara H, Choudhary SK, Dunbar NM, Szczepiorkowski ZM, et al.
Transfusion •
The bites of certain tick species can induce galactose-α-1,3-galactose (alpha-gal) IgE formation. Individuals with alpha-gal IgE can become allergic to meat, a condition termed alpha-gal syndrome. Alpha-gal is structurally related to B antigen. Recent case reports (Gilstad et al., 2023 and Miller et al., 2024) suggest that transfusing group B plasma or platelets to group O individuals with alpha-gal IgE can trigger severe allergic transfusion reactions. However, mechanistic evidence is lacking. A 76-year-old group O man undergoing heart surgery became profoundly hypotensive after receiving 50 mL of a group B platelet unit. He recovered with diphenhydramine treatment. We investigated potential causes of anaphylaxis (alpha-gal syndrome; IgA deficiency; protamine, and rocuronium allergies). The platelet unit and patient samples were analyzed by flow cytometry. Indirect basophil activation tests (iBATs) were performed on the patient's plasma. The patient's serum tryptase level spiked, consistent with anaphylaxis. His serum tested positive for alpha-gal IgE (1.49 kU/L). Flow cytometric analyses demonstrated that: (1) the transfused platelets expressed substantial B antigen, and (2) the patient's plasma contained IgE-recognizing alpha-gal and B antigen > A antigen. In iBATs, resting allogeneic basophils incubated with the patient's plasma showed equivalent (albeit weak) activation when stimulated with either alpha-gal or B antigen. We report a case of anaphylactic shock in an O patient transfused with a B platelet unit. The in vitro data suggest, but do not prove, that the reaction was mediated by recipient alpha-gal IgE. Further studies are needed to establish whether transfusion-related alpha-gal syndrome ("TRAGS") is a true clinical entity.