Alpha-Gal Syndrome and Cardiac Surgery.

Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered. The term "alpha-gal syndrome" (AGS) was then coined to describe allergic reactions to mammalian meat or other alpha-gal-containing products derived from mammals. Symptoms are often delayed several hours from consumption and can be urticarial and/or gastrointestinal. Medications and bioprosthetic inserts derived from mammals were also noted to cause allergic reactions in affected patients. Cardiac surgery, in particular, is considered high risk, given that unfractionated heparin has a bovine or porcine origin and is administered in large doses for cardiopulmonary bypass. Bioprosthetic valves have similar origins and risks. Awareness of AGS in cardiac surgery patients can lead to decreased risk preoperatively and inform management perioperatively and postoperatively. In this narrative review, we have reviewed the published literature relevant to AGS in patients undergoing cardiac surgery and shared our treatment approach.

Unraveling Alpha-Gal Syndrome: A Case Study of a Rare Meat Allergy.

Allergies are a very common pathology and their manifestations consist of a spectrum of presentations, ranging from minimal discomfort like a runny nose to lethal reactions like anaphylaxis and death. Meat allergy is not a very common form of allergy, even though there is a relatively high level of meat consumption. One of the rare forms of non-primate mammalian meat allergy is alpha-gal syndrome (AGS). It is related to IgE antibodies specific for galactose-α-1,3-galactose (α-Gal). It is triggered in sensitized individuals due to multiple bites of lone star tick bites (Amblyomma americanum). Here we present a 63-year-old male with a complaint of recurrent hives and tongue swelling, developed recently after traveling to Twinsburg, OH. There is no significant history of any allergic conditions. Vital signs were stable with a normal physical examination. The patient had normal routine labs including eosinophil count, thyroid-stimulating hormone (TSH), iron panel, and negative HIV. Allergy testing showed normal total IgE but increased levels of IgE for allergens like beef, lamb, and pork (18.4, 6.71, and 7.62 respectively) and greatly increased levels of IgE for alpha-gal (42.7). Sensitization to alpha-gal can cause delayed allergic symptoms upon consuming various non-primate mammalian types of meat, particularly beef, pork, and lamb. Conditions like AGS are rare and can be missed as an initial diagnosis in many patients. A high degree of vigilance is required to diagnose such conditions.

Tick salivary proteome and lipidome with low glycan content correlate with allergic type reactions in the zebrafish model.

Ticks, as hematophagous ectoparasites, can manipulate host immune and metabolic processes, causing tick-borne allergies such as α-Gal syndrome (AGS). Glycolipids with bound galactose-alpha-1-3-galactose (α-Gal) are potential allergenic molecules associated with AGS. Nevertheless, proteins and lipids lacking α-Gal modifications may contribute to tick salivary allergies and be linked to AGS. In this study, we characterized the effect of deglycosylated tick salivary proteins without lipids on treated zebrafish fed with dog food formulated with mammalian (beef, lamb, pork) meat by quantitative proteomics analysis of intestinal samples. The characterization and functional annotations of tick salivary lipids with low representation of glycolipids was conducted using a lipidomics approach. Results showed a significant effect of treatment with saliva and saliva deglycosylated protein fraction on zebrafish abnormal or no feeding (p < 0.005). Treatment with this fraction affected multiple metabolic pathways, defense responses to pathogens and protein metabolism, which correlated with abnormal or no feeding. Lipidomics analysis identified 23 lipid classes with low representation of glycolipids (0.70% of identified lipids). The lipid class with highest representation was phosphatidylcholine (PC; 26.66%) and for glycolipids it corresponded to diacylglycerol (DG; 0.48%). Qualitative analysis of PC antibodies revealed that individuals bitten by ticks were more likely to produce PC-IgG antibodies (p < 0.001). DG levels were significantly higher in tick salivary glands (p < 0.05) compared with tick saliva and salivary fractions. The α-Gal content was higher in tick saliva than in deglycosylated saliva and lipid fractions. These results support a possible role for tick salivary proteins and lipids without α-Gal modifications in AGS.

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.

Neurosurgical Management of Patients with Alpha-Gal Syndrome.

Alpha-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.

Alpha-Gal Syndrome: An Underrated Serious Disease and a Potential Future Challenge.

Over the past decades, red meat allergy, also known as mammalian meat allergy, which manifests differently from classic food allergies, has been reported in different countries and regions, including China. The allergen of this disease is not a protein but an oligosaccharide: galactose-α-1,3-galactose, i.e., alpha-gal or α-gal. Therefore, this clinical syndrome is also called α-gal syndrome (AGS). It clinically manifests as delayed anaphylaxis, i.e., patients generally develop allergic symptoms 2-6 h after ingesting red meat. This clinical manifestation is believed to be related to sensitization to α-gal after tick bites. Sensitized individuals may also develop anaphylaxis after ingesting food and medicine or being exposed to medical equipment containing α-gal, such as cetuximab and gelatin. Here, the literature on AGS is reviewed for a better understanding of its pathogenesis, clinical diagnosis, and treatment.

A case of alpha-gal syndrome: Recall urticaria and 10 years of measurements of IgE to galactose-α-1,3-galactose.

Alpha-gal IgE level can change rapidly. Reassessment of a patient's alpha-gal IgE level may be helpful in the patient's clinical follow-up. Pruritus related to the site of a previous tick bite strengthens the diagnosis of alpha-gal syndrome.

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.

Zebrafish gut microbiota composition in response to tick saliva biomolecules correlates with allergic reactions to mammalian meat consumption.

The α-Gal syndrome (AGS) is an IgE-mediated tick borne-allergy that results in delayed anaphylaxis to the consumption of mammalian meat and products containing α-Gal. Considering that α-Gal-containing microbiota modulates natural antibody production to this glycan, this study aimed to evaluate the influence on tick salivary compounds on the gut microbiota composition in the zebrafish (Danio rerio) animal model. Sequencing of 16 S rDNA was performed in a total of 75 zebrafish intestine samples, representing different treatment groups: PBS control, Ixodes ricinus tick saliva, tick saliva non-protein fraction (NPF), tick saliva protein fraction (PF), and tick saliva protein fractions 1-5 with NPF (F1-5). The results revealed that treatment with tick saliva and different tick salivary fractions, combined with α-Gal-positive dog food feeding, resulted in specific variations in zebrafish gut microbiota composition at various taxonomic levels and affected commensal microbial alpha and beta diversities. Metagenomics results were corroborated by qPCR, supporting the overrepresentation of phylum Firmicutes in the tick saliva group, phylum Fusobacteriota in group F1, and phylum Cyanobacteria in F2 and F5 compared to the PBS-control. qPCRs results at genus level sustained significant enrichment of Plesiomonas spp. in groups F3 and F5, Rhizobium spp. in NPF and F4, and Cloacibacterium spp. dominance in the PBS control group. This study provides new results on the role of gut microbiota in allergic reactions to tick saliva components using a zebrafish model of AGS. Overall, gut microbiota composition in response to tick saliva biomolecules may be associated with allergic reactions to mammalian meat consumption in AGS.

Recurrent Ogilvie Syndrome as a Possible Manifestation of Alpha-Gal Syndrome (AGS) Requiring Surgical Management: A Case Report.

We present a case of a male in his 60s with a history of alpha-gal syndrome (AGS) who presented with recurrent acute colonic pseudo-obstruction, also known as Ogilvie syndrome, and underwent surgical treatment for life-limiting symptoms of colonic distention, constipation, and abdominal pain. Prior to surgery, he was hospitalized multiple times after beef consumption and was diagnosed with Ogilvie syndrome, requiring a colonoscopy with rectal tube placement for symptom resolution. He later underwent a robotic subtotal colectomy with ileocolic anastomosis. Follow-up visits showed improvement in symptoms of constipation and abdominal distention. This case highlights that AGS may lead to severe manifestations, such as recurrent Ogilvie syndrome. Due to the increasing prevalence of AGS and limited data on disease course, further research is needed to determine symptom manifestations and the potential utility of surgery in management.

Milk Fat Globule Proteins Are Relevant Bovine Milk Allergens in Patients with α­Gal 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 by both 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.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Red Meat Hypersensitivity and Probable Alpha-Gal Syndrome: Prevalence Among Adolescents.

INTRODUCTION: It is unknown whether late adolescents represent a particular risk group for the development of red meat hypersensitivity (RMH) and alpha-gal syndrome (AGS). This age group's physiological changes and eating habits could play a determining role. This study aimed to estimate the self-reported prevalence of RMH and probable AGS among late adolescents. METHODS: A cross-sectional study analyzed a sample of 1992 Mexican adolescents between 15 and 18 years of age. The data were obtained with a previously validated questionnaire that asked about the clinical manifestations related to red meat intake. Confidence intervals at 95% (95% CI) were estimated for proportions. RESULTS: In total, there were 19 adolescents with RMH, a prevalence of 1.0% (95% CI: 0.6-1.5%). The main red meats related to symptoms were pork (89.5%), beef (21.1%), lamb (10.5%), and mutton (5.1%). The most frequent manifestations of RMH were gastrointestinal (73.7%), respiratory (63.2%), and cutaneous (63.2%). Once the symptoms were grouped, there were two cases of urticaria (2/19, 10.5%) and six cases with probable anaphylaxis (6/19, 31.6%). Finally, three adolescents were considered probable cases of AGS, which represents a prevalence of 0.15% (95% CI: 0.1-0.4%). CONCLUSION: Although the prevalence of RMH in late adolescents is low, early detection is justified because approximately one-third present with severe symptoms.

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

BACKGROUND: Alpha-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 PRESENTATION: We 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. CONCLUSIONS: This 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.

Perioperative Considerations in Alpha-Gal Syndrome: A Review.

Galactose-⍺-1, 3-galactose (alpha-gal) is an oligosaccharide found in mammalian tissues that causes allergic reactions in patients with alpha-gal syndrome (AGS). AGS is a hypersensitivity reaction notable for both immediate and delayed allergic and anaphylactic symptoms. As a tick-based disease, AGS has gained increasing prevalence across the United States and can have a significant influence on which medications are safe for patients. Many medications used within the operating room and intensive care units have inactive ingredients that can be mammalian-derived and therefore should be vetted before administering to patients with AGS. Management of patients with AGS involves diligent action in the preoperative and perioperative settings to reduce patient exposure to potentially harmful medications. In conducting a comprehensive risk stratification assessment, the anesthesia team should identify any at-risk patients and determine which medications they have safely tolerated in the past. Despite obtaining a complete history, not all patients with AGS will be identified preoperatively. The perioperative team should understand which common medications pose a risk of containing alpha-gal moieties (e.g., heparins, gelatin capsules, vaccines, lidocaine patches, surgifoam, etc.​​). For this reason, this paper includes a compendium of common anesthetic medications that have been cross-referenced for ingredients that have the potential to cause an AGS reaction. Any potentially unsafe medications have been identified such that medical providers can cross-reference with the ingredients listed at their respective institutions.

Epidemiology and the Growing Epidemic of Food Allergy in Children and Adults Across the Globe.

PURPOSE OF REVIEW: Food allergies are immune-mediated, complex disorders, which are the source of increasing health concern worldwide. The goal of this review is to present an updated summary of the food allergy (FA) burden among children and adults across different populations, focusing on research from the past 5 years. RECENT FINDINGS: FAs impact a growing number of global residents-particularly those residing in higher-income, industrialized regions. Moreover, growing epidemiologic evidence suggests that the population health burden of non-IgE-mediated FAs, such as food protein-induced enterocolitis syndrome, may also be higher than previously reported. FA is a complex trait that impacts infants, children, as well as adults across the globe. The population health burden of both IgE- and non-IgE-mediated FAs is likely to grow in the absence of rapid advances and widespread implementation of effective FA prevention and treatment interventions. Systematic epidemiological research initiatives are needed, both nationally and globally, to better understand and reduce the burden of these allergic diseases.

Use of antithymocyte globulin (rabbit) in a patient with known alpha-gal syndrome undergoing allogenic stem cell transplantation.

INTRODUCTION: Alpha-gal syndrome (AGS) is a hypersensitivity disorder in which tick bites-most commonly from the lone star tick (Ambylomma americanum)-trigger immunoglobulin E-mediated hypersensitivity reaction upon exposure to oligosaccharide galactosse-alpha-1,3-galactose (α-gal). α-gal is most notorious for being found in "red meat" products but is present in mammalian meats such as beef, pork, lamb, rabbit, and others. Manifestations of AGS hypersensitivity are variable. There is currently no in vivo data describing allergic reactions against rabbit products in patients with AGS. CASE REPORT: Here, we describe a case of a 44-year-old male with myelodysplastic syndrome and a known history of AGS undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) with the use of rabbit antithymocyte globulin (rATG) for graft-versus-host disease (GVHD) prophylaxis. MANAGEMENT AND OUTCOME: The risk of cross-reactivity against rATG in our patient with AGS could not be ruled out and, therefore, a test dose was administered. The patient tolerated the test dose with no signs of anaphylaxis. After demonstrating tolerance to the test dose, rATG was utilized for GVHD prophylaxis. DISCUSSION: Due to the heterogeneity of AGS manifestations in patients, the use of rATG in patients with known AGS should be considered on a case-by-case basis. The administration of a test dose may help predict the occurrence of severe hypersensitivity reactions. The limited data surrounding the risk of AGS with rabbit-containing products and the various indications for the use of rATG warrants more in-depth study of the reactivity of this medication in this population.

IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.

BACKGROUND: Alpha-gal (Galα1-3Galß1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. OBJECTIVE: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. METHODS: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. RESULTS: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. CONCLUSION: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

Diagnostic validity of specific immunoglobulin E levels to alpha-gal in alpha-gal syndrome: a cross-sectional analysis.

BACKGROUND: The diagnosis of Alpha-gal Syndrome (AGS) is based on the presence of symptoms after being exposed to potential sources of alpha-gal together with values ​​of specific IgE (sIgE) to alpha-gal ≥ 0.1 kUA/L or ≥ 0.35 kUA/L. The aim of this study was to evaluate the diagnostic validity of sIgE levels to alpha-gal ≥ 0.1 kUA/L for identifying AGS. METHODS: This was a cross-sectional analysis of adult patients with available data on sIgE levels to alpha-gal, classified into two groups according to the presence (Group 1) or absence (Group 2) of symptoms after being exposed to potential sources of alpha-gal. Values of sIgE to alpha-gal ≥ 0.1 kUA/l were considered a positive result. A descriptive analysis of internal and external validity parameters was performed in the entire population and adjusted by sex. RESULTS: The study included 33 individuals in Group 1 and 65 in Group 2, with a mean age of around 47 years. The analysis of internal validity parameters revealed a high sensitivity, specificity, and positive probability ratio, with higher sensitivity in men and higher specificity in women. The analysis of external validity parameters showed a high negative predictive value and global value in all populations and both sexes. However, the positive predictive value was relatively high in men, but low in women. CONCLUSIONS: Our results suggest that sIgE levels ≥ 0.1 kUA/L may be a useful tool for the diagnosis of AGS, although other factors and diagnostic techniques should also be considered.