Alpha-gal Syndrome Research Articles

Increasing prevalence of galactose-α-1,3-galactose sensitization in the Danish general adult population.

Alpha-gal syndrome is a novel food allergy to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) present in mammalian meat. Tick bites are considered an important route of sensitization to alpha-gal. Data on alpha-gal sensitization in the general population is scant. We utilized a unique data source of repeated population-based health examination studies to assess prevalence, time trends, risk factors, and characteristics of alpha-gal sensitization. Alpha-gal sensitization was assessed in >11.000 adults from four health examination studies of randomly invited residents in the Copenhagen region conducted in 1990-1991, 2011-2012, 2012-2015, and 2016-2017. Alpha-gal sensitization was defined as serum specific IgE (sIgE) to alpha-gal ≥0.1 kUA/L; ≥0.35 kUA/L; ≥0.7 kUA/L; ≥3.5 kUA/L. The population was characterized according to genetically determined ABO blood group, aeroallergen sensitization, and pets at home. The prevalence of sIgE to alpha-gal ≥0.1 kUA/L was 1.3% in 1990-1991, 3.7% in 2012-2015 and 3.2% in 2016-2017. Of those sensitized to alpha-gal >97% reported to consume red meat at least once a week, even for sIgE to alpha-gal ≥3.5 kUA/L. Male sex, older age, aeroallergen sensitization, cat at home, and blood group A were associated with increased odds of alpha-gal sensitization. The known protective effect of blood group B was confirmed. In this general adult population, the prevalence of alpha-gal sensitization had doubled from 1990-1991 to 2016-2017. This could potentially be due to increased tick exposure and an increased atopic predisposition.

Alpha-Gal Syndrome in a Military Member

Alpha-Gal Syndrome in a Military Member

Extending discussion on alpha-gal syndrome: research needs, clinical significance, and more broad consequences

Extending discussion on alpha-gal syndrome: research needs, clinical significance, and more broad consequences

Mysterious Allergy Caused by Tick Bite: Alpha-Gal Syndrome.

Alpha-Gal syndrome (AGS) manifests as an intricate allergic response characterised by the formation of specific immunoglobulin E (IgE) antibodies targeting a carbohydrate termed galactose-a-1.3-galactose (a-Gal). Alpha-Gal antigens, which play a role in AGS, have been detected in the salivary glands and saliva of various tick species, especially Amblyomma americanum. Identifying these antigens in tick saliva underlines the potential role of tick bites in sensitising individuals to a-Gal and contributes to the complex immunological processes associated with AGS. When people with a-Gal allergy eat beef, pork, lamb, or the flesh of other mammals, they experience an allergic reaction that causes various symptoms, including rash, nausea, vomiting, and diarrhoea. In some cases, AGS can be life-threatening requiring emergency medical attention. Moreover, these reactions do not occur only due to red meat; intake of medical drugs, vaccines, and antidotes containing a-Gal epitopes can also trigger allergies. The fact that the symptoms causing IgE antibodies are directed against a carbohydrate moiety the unusual delay between food consumption and the onset of symptoms, and the differences in the reactions shown by a-Gal allergy make a-Gal syndrome an unprecedented allergic disease and distinguish it from other food allergies. Interestingly, a-Gal antigens involved in the development of AGS have been discovered in salivary secretions of different tick species in several continents. However, the underlying causes of a-Gal-specific IgE production and immune responses to tick bites are not fully understood. This complex system is crucial for identifying and developing new therapies for the disease. This article reviews the evolution of a-Gal, the current understanding of AGS and its relationship to tick species.

The Spread of Lone Star Ticks (Amblyomma americanum) and Persistence of Blacklegged Ticks (Ixodes scapularis) on a Coastal Island in Massachusetts, USA.

In the northeastern USA, the distribution of lone star ticks (Amblyomma americanum) has expanded northward in recent decades, overlapping with the range of blacklegged ticks (Ixodes scapularis). Blacklegged ticks carry pathogens for diseases such as Lyme, babesiosis, and anaplasmosis, while bites from lone star ticks cause other diseases and the alpha-gal syndrome allergy. Lone star ticks can become so abundant that they are perceived as more of a public health threat than blacklegged ticks. Using the island of Martha's Vineyard, Massachusetts, as a case study, we analyzed data from a total of 1265 yard surveys from 2011 to 2024 to document lone star tick presence and subsequent expansion from two peripheral areas, Chappaquiddick and Aquinnah, to all six towns. The timing of lone star tick expansion on Martha's Vineyard closely matched an increase in tick submissions to a pathogen testing center. At Chappaquiddick, drag sampling carried out in June 2023 and 2024 showed that both tick species were most common at wooded sites, where blacklegged nymphs were somewhat more abundant than lone star nymphs. However, lone star ticks occurred in a wider range of natural and peridomestic habitats than blacklegged nymphs, making them far more challenging for people to avoid and manage.

Alpha-gal Syndrome Presenting as Fibromyalgia in an American Indian Population

Alpha-gal Syndrome Presenting as Fibromyalgia in an American Indian Population

Surveillance of ticks (Acari: Ixodidae) and tick-borne pathogens in Eastern Central Alabama.

Similar to other states in the southeastern United States, human cases of tick-borne diseases in Alabama have risen steadily over the last 2 decades. Nevertheless, limited data have been published on ticks or tick-borne pathogen (TBP) distributions since the 1990s. To better understand the risk of tick and TBP exposure in eastern central Alabama, ticks were sampled repeatedly across 8 sites associated with recreational use during May and June of 2015 to characterize tick density and diversity. Although habitats were similar across sites, tick density varied among locations. Seven species were collected, but 97.7% of 1,310 samples were the lone star tick, Amblyomma americanum (L.), the primary vector of ehrlichial agents and the tick species most commonly linked to alpha-gal syndrome and southern tick-associated rash illness. To investigate pathogen prevalence among sites, we tested A. americanum by a multiplex qPCR assay for 5 bacterial species, including 3 Ehrlichia spp. and 2 Rickettsia spp. None of the specimens tested positive for Panola Mountain Ehrlichia or Rickettsia parkeri. However, causative agents of human ehrlichiosis, Ehrlichia chaffeensis and Ehrlichia ewingii, occurred at half of the locations with, respectively, 0.27% and 0.45% of A. americanum infected on average. In contrast, Rickettsia amblyommatis, a tick endosymbiont suspected to be nonpathogenic, was found in 54.5% of the 1119 A. americanum tested. Despite low infection rates of Ehrlichia spp. in A. americanum, high encounter rates with this species in recreational deciduous woodlands suggest a moderate risk of tick bite and a low-to-moderate risk of TBP exposure in late spring.

Identification of Alpha-Gal glycolipids in saliva of Lone-Star Tick (Amblyomma americanum)

Alpha-Gal Syndrome (AGS) is a delayed allergic reaction triggered by IgE antibodies targeting galactose-α-1,3-galactose (α-gal), prevalent in red meat. Its global significance has increased, with over 450,000 estimated cases in the United States alone. AGS is linked to tick bites, causing sensitization and elevated α-gal specific IgE levels. However, the precise mechanisms and tick intrinsic factors contributing to AGS development post-tick bites remain unclear. This study aims to characterize the alpha-gal conjugated lipid antigens in Amblyomma americanum (Am. americanum) salivary glands and saliva. Nanospray ionization mass spectrometry (NSI-MS) analysis revealed the identification of α-gal bound lipid antigens in Am. americanum saliva. Additionally, the activation of basophils by extracted alpha-gal bound lipids and proteins provides evidence of their antigenic capabilities.

The Acari Hypothesis, IV: revisiting the role of hygiene in allergy.

Allergy and its manifestations were first appreciated in the 1870 s. Today, the mechanism by which specific substances elicit allergic reactions remains poorly understood. This is problematic from a healthcare perspective because the prevalence of allergic disease and its societal costs are substantial. Regarding mechanistic understanding of allergy, a new proposal, The Acari Hypothesis, has been forwarded. The Hypothesis, borne from consideration of alpha-gal syndrome, postulates that acarians, i.e., mites and ticks, are operative agents of allergy. By way of their pathogenic payloads and salivary pattern recognition receptor(s), acarians potentiate in human hosts the generation of IgE against acarian dietary elements. Those elements account for most, if not all, known human allergens. Inasmuch as acarian-human interactions occur on human epithelial surfaces, it is to be expected factors that influence the presence and/or operation of acarians on those surfaces influence the expression of allergic diseases. In this report, it is proposed that two adaptations of catarrhine primates, i.e., Old World monkeys, apes and humans, evolved to deter acarian species: firstly, the expansion of eccrine glands across the entirety of body surface area, and, secondly, the secretion of sweat by those glands. Contemporary hygienic practices that reduce and/or disrupt the operation of eccrine glands are likely responsible for the increase in allergic disease seen today.

Neurosurgical Management of Patients with Alpha-Gal Syndrome

AbstractAlpha-gal syndrome (AGS) is an immunoglobulin E–mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients.

Clinical Presentation and Outcomes of Alpha-Gal Syndrome

Background and AimsAlpha-Gal Syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose, primarily linked with lone star tick bites in the US. It presents with symptoms ranging from urticaria and gastrointestinal (GI) manifestations to delayed anaphylaxis following red meat consumption. We aimed to study AGS patients' clinical manifestations, diagnosis, and outcomes. MethodsA retrospective chart review of patients who underwent serological testing for suspected AGS between 2014-2023 at Mayo Clinic was performed. Patients with positive serology were age and sex-matched with those who tested negative. Clinical characteristics of seropositive cohort with and without GI symptoms were compared, and outcomes assessed. ResultsOf 1260 patients who underwent testing, 124 tested positive for AGS. They were matched with 380 seronegative controls. AGS patients reported a higher frequency of tick bites (OR 26.0 [95% CI 9.8-68.3]), prevalence of urticaria (56 % vs. 37%; P=.0008) and were less likely to have asthma (OR 0.4 [0.3 to 0.7]). They had a lower prevalence of heartburn (6% vs. 12%; P=.03) and bloating (6% vs. 13%; P=.03). 47% had GI symptoms and higher proportion were female than those without GI symptoms (69% vs. 35%; P=.002). During a mean follow up of 27 months, 22 of 40 patients reported symptom resolution after avoiding red meat, and 7 were able to transition to regular diet. ConclusionA diagnosis of AGS should be strongly considered in patients with a history of tick bites and clinical presentation of allergic or GI manifestations. Dietary intervention is effective in most but not all patients.

Perioperative Outcomes After Bioprosthetic Valve Replacement in Patients Sensitized to Alpha-gal

BackgroundAlpha-gal syndrome from tick bites, due to sensitivity to alpha-gal, can cause severe allergies. Heart valve implants contain alpha-gal, yet alpha-gal syndrome screening is not standard before valve replacement. This study examines perioperative outcomes in patients with alpha-gal antibodies. MethodsThis is a single-institution prospective cohort study of patients undergoing bioprosthetic aortic valve replacement between January 2022 and January 2023. Anti-alpha-gal immunoglobulin E levels were measured, with primary outcomes being severe allergic reactions and in-hospital mortality, and secondary outcomes including intensive care unit and hospital stay. ResultsOf 155 patients, 32.7% (n = 19) of surgical aortic valve replacement and 29.9% (n = 29) of transcatheter aortic valve replacement patients had detectable immunoglobulin E levels without subsequent serious allergic reactions or in-hospital mortality. Postoperative hospital stay and valve function were similar across groups. ConclusionsIn this study, sensitization to alpha-gal was not associated with serious allergic reactions and did not affect immediate aortic valve function after surgical aortic valve replacement or transcatheter aortic valve replacement.

Alpha-Gal syndrome as a novel food allergy: a case report study

Introduction and importance: Alpha-Gal syndrome (AGS), a distinct form of mammalian meat allergy, presents unique characteristics that set it apart from typical IgE-mediated food hypersensitivities. AGS induces an allergic response typically 3–6 h post-ingestion of mammalian meat, such as beef, pork, or lamb. This prolonged reaction time differentiates AGS from other food allergies, which usually provoke a more immediate response. Case presentation: The authors present a case of a 35-year-old male patient who, unbeknownst to him, had been experiencing symptoms consistent with Alpha-Gal allergy for several years. His symptoms only subsided upon the complete elimination of mammalian meat from his diet. It was only then that the possibility of AGS was considered. Complete abstinence from mammalian meat, meat by-products, and other α-Gal containing foods is the most effective preventative strategy for AGS. No definitive cure for AGS has been established as of now. Treatment protocols for hypersensitivity reactions are contingent upon the severity of the reaction, with therapies ranging from antihistamine medications to the administration of epinephrine. Conclusion: There is considerable variability among AGS patients concerning the consumption of dairy products. Some individuals with AGS can safely consume dairy products without any adverse reactions, while others are advised to abstain due to potential allergenic responses. This variability in dairy tolerance among AGS patients warrants further investigation.

Mammalian Meat Allergy and IgE to Alpha-Gal in Central Virginia: Findings From a COVID-19 Vaccine and Patient Cohort

IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked to tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The alpha-gal syndrome (AGS) is recognized as being common in the southeastern United States. However, prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. Here we characterized the prevalence as well as the presentation and risk factors of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regard to the history of allergic disease. Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. We used ImmunoCAP for IgE assays and assessed the ABO blood group by reverse typing using stored serum. We also investigated biobanked serum from COVID-19 patients. Median age of the 267 enrollees was 42 years, 76% were female, and 43 (16%) were sensitized to alpha-gal (cutoff of 0.1 IU/mL), of which mammalian meat allergy was reported by seven (2.6%). Sensitized subjects (1) were older, (2) had higher total IgE levels but a similar frequency of IgE to common respiratory allergens, and (3) were more likely to report tick bites than were nonsensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat-allergic than nonallergic subjects (geometric mean, 9.0 vs 0.5 IU/mL; P< .001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. In central Virginia, AGS is a dominant cause ofadult food allergy with a prevalence approaching or exceeding2%.

Consider Alpha-gal Syndrome in Patients with Delayed Allergic Reactions after Tick Exposure

Consider Alpha-gal Syndrome in Patients with Delayed Allergic Reactions after Tick Exposure

Emerging Trends in Information-Seeking Behavior for Alpha-Gal Syndrome: Infodemiology Study Using Time Series and Content Analysis.

Alpha-gal syndrome is an emerging allergy characterized by an immune reaction to the carbohydrate molecule alpha-gal found in red meat. This unique food allergy is likely triggered by a tick bite. Cases of the allergy are on the rise, but prevalence estimates do not currently exist. Furthermore, varying symptoms and limited awareness of the allergy among health care providers contribute to delayed diagnosis, leading individuals to seek out their own information and potentially self-diagnose. The study aimed to (1) describe the volume and patterns of information-seeking related to alpha-gal, (2) explore correlations between alpha-gal and lone star ticks, and (3) identify specific areas of interest that individuals are searching for in relation to alpha-gal. Google Trends Supercharged-Glimpse, a new extension of Google Trends, provides estimates of the absolute volume of searches and related search queries. This extension was used to assess trends in searches for alpha-gal and lone star ticks (lone star tick, alpha gal, and meat allergy, as well as food allergy for comparison) in the United States. Time series analyses were used to examine search volume trends over time, and Spearman correlation matrices and choropleth maps were used to explore geographic and temporal correlations between alpha-gal and lone star tick searches. Content analysis was performed on related search queries to identify themes and subcategories that are of interest to information seekers. Time series analysis revealed a rapidly increasing trend in search volumes for alpha-gal beginning in 2015. After adjusting for long-term trends, seasonal trends, and media coverage, from 2015 to 2022, the predicted adjusted average annual percent change in search volume for alpha-gal was 33.78%. The estimated overall change in average search volume was 627%. In comparison, the average annual percent change was 9.23% for lone star tick, 7.34% for meat allergy, and 2.45% for food allergy during this time. Geographic analysis showed strong significant correlations between alpha-gal and lone star tick searches especially in recent years (ρ=0.80; P<.001), with primary overlap and highest search rates found in the southeastern region of the United States. Content analysis identified 10 themes of primary interest: diet, diagnosis or testing, treatment, medications or contraindications of medications, symptoms, tick related, specific sources of information and locations, general education information, alternative words for alpha-gal, and unrelated or other. The study provides insights into the changing information-seeking patterns for alpha-gal, indicating growing awareness and interest. Alpha-gal search volume is increasing at a rapid rate. Understanding specific questions and concerns can help health care providers and public health educators to tailor communication strategies. The Google Trends Supercharged-Glimpse tool offers enhanced features for analyzing information-seeking behavior and can be valuable for infodemiology research. Further research is needed to explore the evolving prevalence and impact of alpha-gal syndrome.

Milk Fat Globule Proteins Are Relevant Bovine Milk Allergens in Patients with α‐Gal Syndrome

Alpha-gal syndrome (AGS) is a mammalian meat allergy associated with tick bites and specific IgE to the oligosaccharide galactose-α-1,3-galactose (α-gal). Recent studies have shown that 10-20% of AGS patients also react to the dairy proteins. Considering the already described role of the meat lipid fraction in AGS manifestations, the aim of this work has been to investigate whether the milk fat globule proteins (MFGPs) could be involved in AGS. The MFGPs are extracted and their recognition by the IgE of AGS patients is proved through immunoblotting experiments. The identification of the immunoreactive proteins by LC-HRMS analysis allows to demonstrate for the first time that butyrophillin, lactadherin, and xanthine oxidase (XO) are α-gal glycosylated. The role of xanthine oxidase seems to be prevalent since it is highly recognized byboth the anti-α-gal antibody and AGS patient sera. The results obtained in this study provide novel insights in the characterization of α-Gal carrying glycoproteins in bovine milk, supporting the possibility that milk, especially in its whole form, may give reactions in AGS patients. Although additional factors are probably associated with the clinical manifestations, the avoidance of milk and milk products should be considered in individuals with AGS showing symptoms related to milk consumption.

Alpha-gal syndrome: exploring the link between tick bites and red meat allergy

Introduction: Alpha-gal syndrome (AGS) arises from tick bites, triggering excessive IgE antibodies to galactose-α-1,3-galactose (α-Gal). Symptoms vary, often appearing post-α-Gal ingestion, ranging from mild to severe, including urticaria, angioedema and respiratory issues. Delayed symptom onset complicates diagnosis, posing challenges for patients. AGS can also result from contact with medical animal-derived products, such as bovine-derived heart valves, necessitating heightened healthcare provider awareness, especially in tick-exposed regions. Management involves allergen avoidance and emergency medications like epinephrine. Further research is needed to refine diagnostic and therapeutic approaches. Purpose: Through literature review and clinical presentation description, we aim to raise awareness and enhance understanding of alpha-gal syndrome. Description of the state of knowledge: AGS, an emerging atypical food allergy, stems from immune reactions to α-Gal oligosaccharide in mammalian meat and other animal products. Avoiding medical items containing alpha-gal is crucial to prevent iatrogenesis. Summary: Understanding AGS etiology and symptoms is vital for diagnosis and management. Healthcare providers' lack of awareness may lead to underdiagnosis, inadequate patient care, and underestimation of affected individuals.

Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

Alpha gal syndrome, a relative not absolute contraindication to the use of bovine pericardium to close an intracardiac septal defect: a case report

BackgroundAlpha-gal syndrome is an allergic condition in which individuals develop an immune-mediated hypersensitivity response when consuming red meat and its derived products. Its diagnosis is important in individuals undergoing cardiac surgery, as patients frequently require large doses of unfractionated heparin or the insertion of surgical implants, both of which are porcine or bovine in origin. There are currently no guidelines for heparin administration in alpha-gal patients, with even less knowledge regarding the long-term clinical implications of these patients after receiving bioprosthetic valve replacements or other prostheses.Case presentationWe present the case of a 31-year-old male who underwent cardiac surgery in the setting of alpha-gal syndrome for a large atrial septal defect (ASD) and mitral valve prolapse (MVP). The patient continues to do well one year after undergoing a mitral valve repair, tricuspid valve repair and an ASD closure using bovine pericardium. He sustained no adverse reaction to the use of heparin products or the presence of a bovine pericardial patch. This rare case was managed by a multidisciplinary team consisting of cardiothoracic surgery, cardiac anesthesiology, and allergy/immunology that led to an optimal outcome despite the patient’s pertinent allergic history.ConclusionsThis case highlights that the use of bovine pericardium and porcine heparin to close septal defects in patients with milder forms of alpha-gal allergy can be considered if other options are not available. Further studies are warranted to investigate the long-term outcomes of such potential alpha-gal containing prostheses and heparin exposure and establish the optimal decision making algorithm and prophylactic regimen.