# Alpha-gal sensitization and allergic transfusion reactions: a scoping review protocol

## TL;DR

This study explores how tick bites can cause an allergy to alpha-gal, which may lead to allergic reactions during blood transfusions.

## Contribution

The paper introduces a scoping review protocol to investigate transfusion-related alpha-Gal syndrome and its diagnostic challenges.

## Key findings

- Tick bites may cause alpha-gal sensitization leading to allergic reactions.
- Alpha-gal syndrome could be linked to blood transfusion reactions.
- Diagnostic methods for alpha-gal allergy may also apply to transfusion-related cases.

## Abstract

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: 10.17605/OSF.IO/WDZT6).

The online version contains supplementary material available at 10.1186/s13643-026-03134-9.