University of Missouri

α-Gal Syndrome in the South: Why We Need Treatment Trials, Not Just Tick Prevention.

α-Gal syndrome (AGS), a tick bite-associated allergy to mammalian meat, affects an estimated 450,000 Americans, with the highest prevalence concentrated in the US South and Southeast. The lone star tick (), ubiquitous across the region, transmits AGS sensitization, making reexposure nearly inevitable for outdoor workers and residents. Current management relies on dietary avoidance of mammalian products of an indeterminant length, a recommendation that is neither practical in a region where mammalian meat is central to cuisine and culture nor evidence based regarding duration or necessity. In the absence of treatment options, patients are turning to alternative interventions such as acupuncture protocols that lack validation from controlled trials. Meanwhile, oral immunotherapy has demonstrated safety and efficacy for other immunoglobulin E-mediated food allergies, and individual case reports suggest desensitization may be feasible for AGS syndrome. The US South, with its high disease burden, clinical expertise, and patient populations, is uniquely positioned to lead the rigorous phase 1 and phase 2 trials needed to develop evidence-based treatment alternatives. Without such research, patients have only dietary restriction as an evidence-based option and may seek purported treatments that lack rigorous validation.

Digital Health Solutions for Alpha-Gal Syndrome: A Scoping Review of Telemedicine Evidence and Applications.

Alpha-gal syndrome (AGS) is an emerging allergy initiated by tick bites that leads to delayed IgE-mediated hypersensitivity reactions to galactose-α-1,3-galactose (α-gal), a carbohydrate present in mammalian tissues. Symptoms are highly variable and include urticaria, gastrointestinal distress, and life-threatening anaphylaxis. Diagnosis relies on patient history and serological testing for α-gal-specific IgE antibodies. This scoping review, following PRISMA methodology, evaluates telemedicine for clinical management of AGS. The syndrome's characteristic delayed response pattern poses distinct challenges for standard allergy management protocols. Telehealth presents compelling solutions by enabling structured follow-up, remote data collection, and patient support, which is especially critical given that AGS is concentrated in geographic areas with limited specialist access and low provider familiarity. A case study of successful AGS desensitization using remotely monitored oral immunotherapy provides proof-of-principle for telemedicine's transformative potential. Integrating telehealth is a strategic approach to improve diagnosis, facilitate long-term management, and strengthen surveillance for this increasingly prevalent condition.

Alpha-gal syndrome across the lifespan: Distinct pediatric clinical patterns and rural predominance in Midwestern patients.

Novel Case Presentation of Abulia After Lone Star Tick Bite As Evidenced by Raised Titers of Alpha-Gal Specific IgM Immunoglobulin and a Possibility of Alpha-Gal Driven Hypothalamic Dysfunction As the Pathomechanism.

Galactose-α-1,3-galactose, an oligosaccharide epitope better acknowledged as α-Gal, is present in non-primate mammal meat, tick bites, microorganisms, and vaccines as a glycoprotein or glycolipid moiety. This can manifest hyperimmune reactions as it enters the human body, known as α-Gal syndrome (AGS). AGS and Guillain-Barré syndrome share cognate immunogenic pathomechanism via conquering immune tolerance further speculating galactose navigated neurological sequel. Unusual symptomatic presentation of abulia in our case, with incidental finding of high titers of α-Gal specific IgE immunoglobulin further supported by temporal resolution of symptoms on abstinence of meat products, raises a high degree of suspicion of neuro-psychiatric manifestation in sensitized α-Gal patients. The pathomechanism is blurry, and an absence of an objective diagnostic tool makes the neurological diagnosis challenging. α-Gal driven immune-related hypothalamic dysfunction could be a possibility that needs further exploration and is a topic of research.

The clinical presentation of alpha-gal allergy among pediatric patients with food allergy in southwest Missouri.

Carbohydrate-mediated binding and induction of acrosomal exocytosis in a boar sperm-somatic cell adhesion model.

The molecular basis underlying the binding of spermatozoa to their homologous eggs and the subsequent induction of acrosomal exocytosis remain a major unresolved issue in mammalian fertilization. Novel cell adhesion systems are now being explored to advance this research. Triantennary and tetraantennary N-glycans have previously been implicated as the major carbohydrate sequences that mediate the initial binding of spermatozoa to the specialized egg coat (zona pellucida) in the murine and porcine models. Mouse spermatozoa also undergo binding to rabbit erythrocytes (rRBCs), presumably via the interaction of their lectin-like egg-binding proteins with branched polylactosamine sequences present on these somatic cells. Experiments presented in this study confirm that boar spermatozoa also bind to rRBCs. However, unlike mouse spermatozoa, boar spermatozoa also undergo acrosomal exocytosis within 30 min after binding to rRBCs. Both binding and induction of acrosomal exocytosis in this system did not require the participation of terminal Galalpha1-3Gal sequences that are found on rRBCs. Pronase glycopeptides derived from rRBCs inhibited the binding of boar sperm to porcine oocytes by 91% at a final concentration of 0.3 mg/ml under standard IVF conditions. Binding in this porcine cell adhesion model was also completely blocked at this concentration of glycopeptide. Thus, adhesion results from the interaction of the egg-binding protein expressed on the surface of boar spermatozoa with the glycans presented on rRBCs. This cell adhesion model will be useful for investigating the molecular basis of gamete binding and the induction of acrosomal exocytosis in the pig.

Analysis of protein-linked glycosylation in a sperm-somatic cell adhesion system.

Murine sperm initiate fertilization by binding to the specialized extracellular matrix of their complementary eggs, known as the zona pellucida. On the basis of data reported in this study, mouse sperm also bind to rabbit erythrocytes with higher affinity than they do to murine eggs. This unusual interaction between a germ cell and a somatic cell ("sperm-somatic cell adhesion system") is also carbohydrate dependent based on its sensitivity to mild periodate oxidation. To determine what types of carbohydrate sequences could be involved in this interaction, the protein-linked oligosaccharides of rabbit erythrocytes were sequenced using novel matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry methods that enabled the analysis of individual components up to m/z 9000. The N-glycans are primarily complex biantennary and triantennary types terminated with Galalpha1-3Gal sequences. The majority of these oligosaccharides also possess one antenna consisting of a highly branched polylactosamine-type sequence that is also associated with many glycosphingolipids that coat rabbit erythrocytes. These erythrocytes also express Core 1 and Core 2 O-glycans terminated primarily with Galalpha1-3Gal sequences and to a lesser extent sialic acid. These results confirm that rabbit erythrocytes and mouse eggs present very different types of carbohydrate sequences on their surfaces. However, oligosaccharides terminated with beta1-6-linked N-acetyllactosamine or its alpha1-3 galactosylated analog are expressed on both the mouse zona pellucida and this somatic cell type. The far more abundant presentation of such sequences on rabbit erythrocytes compared with murine eggs could explain why mouse sperm display such exceptional affinity for this somatic cell type.