Miller MJ, Price C, Shields TC, Zarpak R, Lee P, et al.
Systematic reviews •
Tick bites may expose individuals to a carbohydrate not found in humans, galactose-alpha-1,3-galactose (alpha-gal). A spectrum of disorders may result from IgE-mediated hypersensitivity reactions to alpha-gal, including alpha-gal syndrome (AGS), an allergy to meat or meat-derived products usually presenting 2-6 h after consuming the product plus positive alpha-gal specific IgE testing for the oligosaccharide. Reports of anaphylaxis in group O recipients of group B plasma in the absence of other risk factors for severe allergic reactions to blood transfusion could be alpha-gal sensitization; the allergen galactose-alpha-1,3-galactose (Gal-alpha-1-3Galβ1-(3)4GlcNAc-R) is antigenically similar to the B blood group antigen (Gal-alpha-1-3(Fuc-alpha-1,2)Gal). The potential cross-reactivity of alpha-gal specific IgE to B type red blood cells may pose a safety consideration for blood donation and transfusion. This scoping review protocol will be used to research all publications on alpha-gal sensitization to (1) describe characteristics of all known cases of transfusion-related alpha-Gal syndrome (TRAGS) and hypersensitivity reactions to infusions of mammalian red meat-derived medical products besides blood components that may resemble TRAGS; (2) identify studies that explore possible relationships between alpha-gal sensitization and blood group that may be relevant to understanding TRAGS; (3) describe which clinical, laboratory, and epidemiologic parameters used to diagnose AGS food allergy are also appropriate to diagnose TRAGS; and (4) identify which diagnostic assays exist for AGS and how they are used for AGS and/or TRAGS. Using peer-reviewed search strategies, our study team will perform a scoping review with no date or language limit of all literature relevant to the research objectives in PubMed, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, including title, abstract, full-text screening, and data collection using Covidence. This study involves published data predominantly from humans (and, rarely, animal) studies of diagnostic assays in development for use in humans. It does not require institutional review board or ethics approval. We intend to disseminate our findings to specialists in allergy, immunology, hematology, and blood banking and to patients or blood donors experiencing symptoms of alpha-gal sensitization. Open Science Framework (osf.io) (DOI: https://doi.org/10.17605/OSF.IO/WDZT6 ).
Miller MJ, Zarpak R, Lee P, Osterwind Z, Lenz M, et al.
Journal of translational medicine •
BACKGROUND: Tick bites may expose individuals to a carbohydrate not found in humans, galactose-alpha-1,3-galactose (alpha-gal), including allergy to mammalian red meat or red meat-derived products presenting 2–6 hours after consuming the product plus positive alpha-gal specific IgE testing that may indicate alpha-gal syndrome (AGS). Anaphylaxis in group O recipients of group B blood products in the absence of other risk factors for allergic transfusion reactions could be transfusion-related alpha-gal syndrome (TRAGS); galactose-alpha-1,3-galactose (Gal-alpha1-3 Galβ1-(3)4GlcNAc-R) is similar to the B blood group antigen (Gal-alpha1-3(Fuc-alpha-1,2)Gal). OBJECTIVES: To review scientific and grey literature with no date or language limit to: 1) describe characteristics of all known cases of transfusion-related alpha-gal syndrome (TRAGS) and hypersensitivity reactions to infusions of mammalian red meat-derived medical products besides blood components that may resemble TRAGS; 2) identify studies that explore possible relationships between alpha-gal sensitization and blood group that may be relevant to understanding TRAGS; 3) describe which clinical, laboratory, and epidemiologic parameters used to diagnose AGS food allergy are also appropriate to diagnose TRAGS; and 4) identify which diagnostic assays exist for AGS and how they are used for AGS and/or TRAGS. METHODS: Using search strategies peer-reviewed by biomedical librarians we performed a scoping review of literature in five medical databases, charted in Microsoft Excel and Covidence software. RESULTS: Of 11732 studies imported for screening, 3858 duplicates were removed and 7874 papers were screened. Title and abstract screening excluded 7383 papers. Full-text screening excluded 380 papers. Of the included papers, 20/111 (18%) addressed risk for alpha-gal allergy by blood group and 18/111 diagnostics (16%). CONCLUSION: A comprehensive literature review showed a possible association between alpha-gal allergy and blood group. Further guidance is needed regarding potential clinical implications.
Miller MJ, Lee P, Lee BG, Flegel WA, West-Mitchell K, et al.
Transfusion •
The U.S. Centers for Disease Control and Prevention (CDC) has reported increasing rates of alpha-gal syndrome, an allergic response after meat ingestion (AGS). AGS has been associated with prior exposure to tick bites or other biologics characterized by a life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal) an oligosaccharide structurally similar to the group B antigen on red blood cells (RBC) found in most non-primate mammalian meat and products derived from these mammals. In 2023, Transfusion reported 3 group O recipients of group B plasma in the Washington, D.C. metropolitan area with no history of meat allergy who had anaphylactic transfusion reactions compatible with AGS. We investigated allergic reactions in 2 additional patients who received ABO minor-incompatible blood products at 2 hospitals in the D.C. area during fall 2023. For both patients, a medical chart review was performed and IgE levels to alpha-gal were measured. The first patient, a 64-year-old, O-positive patient status post heart transplant with no known allergies, was admitted with acute COVID-19 induced antibody-mediated transplant rejection and placed on extracorporeal membrane oxygenation (ECMO). While undergoing plasma exchange (PLEX) (50% albumin/50% fresh frozen plasma (FFP)), the patient tolerated 2 units of group O FFP and 1 unit of group A FFP before becoming hemodynamically unstable during transfusion of 1 unit of B-positive FFP. PLEX was stopped. The patient later died of sepsis from underlying causes. The second patient, a 57-year-old O-positive man with a history of melanoma and neuro fibromatosis type 1, was undergoing an abdominal resection including transfusion of 3 units of O-positive RBC when he suffered hypotension and ventricular tachycardia requiring intraoperative code after receiving 2 units of group B FFP. Hiveswere noted after resuscitation. The patient had a history of tick bites but no known allergies. He is alive 5 months after the possible allergic event. Both patients had full transfusion reaction evaluations and immunology testing results above the positive cutoff for anti-alpha-gal IgE. Two patients with O-positive blood and no known allergies experience danaphyl axis after transfusion with group B FFP. The symptoms cannot definitively be imputed to an allergic transfusion reaction, but the presence of IgE against alpha-gal supports an association. Medicating patients with antihistamines and IV steroids pre-transfusion may prevent allergic reactions. Restricting group B plasma-containing products (plasma, platelets, cryoprecipitate) for patients who experience AGS-like symptoms may be considered.
Yoshida Y, Yang J, Peaker PE, Kato H, Bush CA, et al.
The Journal of biological chemistry •
The coaggregation receptor polysaccharides (RPS) of Streptococcus oralis and related species are recognized by lectin-like adhesins on other members of the oral biofilm community and by RPS-specific antibodies. The former interactions involve beta-GalNAc or beta-Gal containing host-like motifs in the oligosaccharide repeating units of these polysaccharides, whereas the latter involves features of these molecules that are immunogenic. In the present investigation, the molecular and corresponding structural basis for the serotype specificity of S. oralis ATCC 10557 RPS was determined by engineering the production of this polysaccharide in transformable Streptococcus gordonii 38. This involved the systematic replacement of genes in the rps cluster of strain 38 with different but related genes from S. oralis 10557 and structural characterization of the resulting polysaccharides. The results identify four unique genes in the rps cluster of strain 10557. These include wefI for an alpha-Gal transferase, wefJ for a GalNAc-1-phosphotransferase that has a unique acceptor specificity, wefK for an acetyl transferase that acts at two positions in the hexasaccharide repeating unit, and a novel wzy associated with the beta1-3 linkage between these units. The serotype specificity of engineered polysaccharides correlated with the wefI-dependent presence of alpha-Gal in these molecules rather than with partial O-acetylation or with the linkage between repeating units. The findings illustrate a direct approach for defining the molecular basis of polysaccharide structure and antigenicity.