Publications Database
Research on Alpha-gal Syndrome
(the Mammalian Meat Allergy)
With this publications database, we hope to consolidate all the peer-reviewed research on alpha-gal syndrome, as well as select publications on related topics such as:
- pork-cat syndrome and other mammalian meat allergies
- other carbohydrate allergies
- cross-reactive carbohydrate determinants
- the role of ecto- and endoparasites in inducing food allergy
- vector management and ecology
- the evolution of the α-gal immune response
- allergy and autoimmune disease
- hypersensitivity reactions to biologics
- co-factors
- idiopathic anaphylaxis
- airborne reactions to food allergens
- carrageenan, mammalian byproducts, cross-contamination of meat products, and other relevant food and food industry issues
- viral glycan shields and the development of drugs and vaccines employing the α-gal immune response
- xenotransplantation and the development of knock-out pigs
Some gray literature and relevant government, industry, and nonprofit documents were included.
Thanks to Lee Ann Kendrick, Matthew von Hendy, and John Bianchi of Revivicor for their assistance with the initial creation of this database.
Stars indicate publications flagged as important or of interest in one or more review articles by Commins SP, Hilger C, Platts-Mills TAE, and van Nunen S, and/or deemed as such by the database manager.
* of interest
** of significant interest
† of special relevance to emergency care/perioperative care/hospitalization/pharmacy
‡ of special relevance to diagnosis and management
§ key review articles
Please report errors or omissions to alphagalinformation@gmail.com.
| AUTHORS | DATE | TITLE & ABSTRACT | PUBLICATION/LINK | KEYWORDS |
|---|---|---|---|---|
| Gabrielli A, Candela M, Pisani E, et al. | 1992 | Antibodies against terminal galactosyl (alpha 1-3) galactose epitopes in systemic sclerosis (scleroderma). |
Clin Exp Rheumatol. 1992;10(1):31. | systemic sclerosis; scleroderma; autoimmune; rheumatology |
| Abdelghany Y, Resnyk J, Nadi Khalil A, Zimrin A, Rose JJ. | 2024 | A Case of Anaphylaxis Associated Thrombocytopenia. C32. ALL THAT WHEEZES (AND THEN SOME): CASE STUDIES. |
C32. ALL THAT WHEEZES (AND THEN SOME): CASE STUDIES. American Thoracic Society International Conference Abstracts. American Thoracic Society; 2024:A5290-A5290. | thrombocytopenia; enoxaparin; heparin |
| Abreu C, Bartolomé B, Cunha L, Falcão H. | 2018 | Galactose-alpha-1,3-galactose allergy: a rare syndrome and an atypical presentation. Summary: Allergies to red meat associated with galactose-alpha-1,3-galactose, commonly known as alpha-gal, are rare and have only recently been described. At this time, the literature reports only one case documented in Portugal. In this study, we report the case of a 76-year-old male with an immediate reaction following the ingestion of red meat. Rigorous diagnostic exams, including prick test, prick-to-prick tests, serum specific IgE and SDS-PAGE IgE-immunoblotting, were performed. The alpha-gal epitope IgE re-turned a value of 35.3 kUA/L, leading the authors to believe that this is an atypical case of alpha-gal allergy. |
European annals of allergy and clinical immunology. 2018 Jul;50(4):190-2. | Bartolome; Falcao; Europe; Portugal; rapid onset reaction; immediate reaction; no tick bite; unknown vector |
| Abreu C, Cunha L, Bartolomé B, Falcão H. | 2015 | Anaphylaxis after consumption of red meat in patient with IgE antibodies specific for galactose-alpha-1,3-galactose. | Allergy: European Journal of Allergy and Clinical Immunology. 2015 Sep;70:616-7. | Bartolome Falcao |
| Adams CB, Street DS, Crass M, Bossaer JB. | 2016 | Low rate of cetuximab hypersensitivity reactions in Northeast Tennessee: An Appalachian effect? Purpose: Cetuximab is a monoclonal antibody with a known risk of hypersensitivity reactions. Early studies showed hypersensitivity reaction rates of 3%, but there appears to be a higher incidence in the southeastern United States. To confirm the findings from nearby institutions that cetuximab-associated hypersensitivity reactions occur in approximately 20% of patients in the southeastern United States. Methods: A retrospective chart review was conducted at Johnson City Medical Center in Johnson City, Tennessee. Each patient's first infusion was analyzed for hypersensitivity reaction, as well as for demographic information such as allergy and smoking history, pre-medications, and malignancy type. Results: Data from the first infusion of cetuximab were collected for a total of 71 patients with various malignancies. The overall rate of grade 3 or higher hypersensitivity reaction was 1.4%, and total rate of hypersensitivity reaction was 8.5%. These findings more closely correlate to the early clinical trials and package insert. Both severe (p=0.001) and any-grade (p=0.002) hypersensitivity reaction occurred less frequently in one Southeastern Appalachian medical center compared to academic medical centers directly to the east and west. Conclusions: Patients in southern Appalachia may be less likely to develop cetuximab hypersensitivity reactions compared to surrounding areas in the Southeastern U.S. These results lend support to the theory that exposure to lonestar ticks (Amblyomma americanum) may be responsible for the development of IgE antibodies to cetuximab that cause hypersensitivity reactions. The development of quick and reliable bedside predictors of cetuximab hypersensitivity reactions may aid clinicians considering the use of cetuximab. |
Journal of Oncology Pharmacy Practice. 2016 Dec;22(6):784-9. | pharmacy; pharmaceutical; medication; biologic; biological agent; monoclonal antibody; mAb; cetuximab; prevalence; Tennessee; Appalachia |
| Adegoke A, Kumar D, Budachetri K, Karim S. | 2021 | Changes in microbial composition, diversity, and functionality in the Amblyomma maculatum microbiome following infection with Rickettsia parkeri. Background: Ticks are the primary vectors for emerging and resurging pathogens of public health significance worldwide. Examining tick bacterial composition, diversity, and functionality across developmental stages and tissues is necessary for designing new strategies to control ticks and prevent tick-borne diseases. Methods: A high-throughput sequencing approach was used to determine the influence of blood meal and Rickettsia parkeri infection on changes in Amblyomma maculatum microbiome composition, diversity, and functionality across the developmental timeline and in different tissues. Quantitative insight into microbial ecology analysis allowed us to determine microbial population structure, composition, and diversity. A non-metric multidimensional scaling, the sparse correlations for compositional data (SparCC) module, and phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) software were used in the assessment. . Results: The Amblyomma maculatum microbiome comprises ten bacterial genera present across tick life cycle stages. Among the top ten bacterial genera (the core tick microbiome), Rickettsia, Francisella, and Candidatus Midichloria are the key players, with positive interactions within each developmental stage and adult tick organ tested. The bacterial abundances, based on the number of operational taxonomic units (OTUs), increase with blood meal in each stage, helping bacterial floral growth. The growth in bacterial numbers is related to highly abundant energy metabolism orthologs with blood meal, according to functional analysis. Whereas R. parkeri had a positive correlation with Candidatus Midichloria during the tick life cycle, based on the increased number of OTUs and network analysis, this was due to an increased level of metabolic activity. Interestingly, R. parkeri replaces Francisella, based on the lower level of OTUs representing Francisella in R. parkeri-infected ticks (in all stages/organs) and negatively correlated according to network and linear discriminant analysis effect size (LEfSe). br> Conclusions: We found that Rickettsia and Francisella predominate in the core microbiome of the Gulf Coast tick, whereas Candidatus Midichloria and Cutibacterium levels increase with infection. Network analysis and functional annotation suggest that R. parkeri interacts positively with Candidatus Midichloria and negatively with Francisella and that metabolic profiles are upregulated with blood meal and R. parkeri infection. Overall, this is the first study to determine the combinatorial outcome of blood meal and pathogen interaction on microbiome composition over the developmental stages of Am. maculatum. This new study expands on our existing knowledge of the Am. maculatum microbiome and further highlights the need to investigate pathogen–symbiont interactions between R. parkeri and Francisella or Candidatus Midichloria to facilitate the development of strategies for controlling tick-transmitted diseases. |
bioRxiv 2021.10.25.465777 | Amblyomma maculatum; tick biome |
| Afshan T, Kelbel T. | 2019 | M301 ALLERGIC REACTION WHILE MAKING BURGERS—BLAME IT ON THE DOG!. Introduction: A 5-year-old girl with history of significant eczema, severe dog allergy (IgE>100), and anaphylactic allergy to egg and treenuts developed urticaria on her bilateral arms after preparing hamburger patties. No other ingredients, such as egg, were handled. She had previously tolerated cooked beef and had no history of milk allergy. Case Description: Why, in the absence of milk allergy, was this patient able to tolerate cooked beef ingestion but developed urticaria after raw beef exposure? Diagnostic Plan: Initial diagnostics for beef allergy included beef extract skin testing and beef IgE blood testing, both of which were negative. IgE blood tests for α-Gal, pork, and venison were also negative. The patient passed an oral food challenge to cooked beef. Subsequent skin testing for raw beef was positive (5mm x 10mm). Discussion: Mammalian meat allergy is overall rare, and is frequently associated with α-Gal allergy. A relationship between mammalian meat and epithelia has been described infrequently and is thought to be due to serum albumin cross-reactivity. There is one previous case of an adult cook who developed wheezing and contact urticaria after exposure to raw beef, had previously tolerated cooked beef ingestion, and was subsequently found to have positive skin testing to raw beef. Given structural similarities between mammalian albumins and prior described relationships (i.e. cat and pork), further study would be beneficial to better understand this possible connection. Conclusion: To the best of our knowledge, this is the first pediatric case of raw beef allergy coinciding with severe dog allergy. |
Annals of Allergy, Asthma & Immunology. 2019 Nov 1;123(5):S124. | |
| Ahlers C, Parker E. | 2023 | 41761 Alpha-gal Syndrome for the Dermatologist. Note: this is an abstract only. |
Journal of the American Academy of Dermatology. | dermatology |
| Ahmady A, Yashi K, Virk JP, Roudabeh K, Parikh T. | 2023 | A Case Report on Alpha-gal Syndrome. The alpha-Gal syndrome (AGS) is a relatively newly recognized food allergy in which patients develop sensitization to meat after being bitten by specific tick species. AGS causes a delayed IgE mediated allergic reaction after consumption of meat and sometimes-dairy products and currently it is treated by avoiding consumption of allergens. Here we present a patient who has been living with AGS for about 20 years. |
Curr Res Cmpl Alt Med. 2023;7(178):2577-201. | case report; Kansas; chicken |
| Ailsworth S, Noth A, Patel J, Workman L, Keshavarz B, Nelson M, Platts-Mills T, Susi A, Nylund C, Wilson J. | 2023 | Association of Sex and ABO-blood Group with Alpha-Gal Sensitization in a Cohort of Military Personnel. Rationale: IgE antibodies to galactose-alpha-1,3-galactose (alpha-gal) are strongly linked with tick bites and cause a syndrome of mammalian meat allergy. Previous reports suggest that male sex is associated with alpha-gal sensitization, whereas B blood group is protective. We sought to investigate these associations in a large military cohort. Methods: Baseline and follow-up serum samples (median 3.5 years) were collected and stored in the Department of Defense Serum Repository from 3000 personnel stationed at 10 military bases in the central/eastern USA. Alpha-gal IgE (cut-off 0.1 kU/L) was measured by ImmunoCAP and ABO-blood group assessed by reverse-typing in a subset of the cohort. Results: Of the 3000 subjects, median age was 19 years (IQR 18-22), 2456 (82%) were male, 179 (6.0%) were sensitized to alpha-gal at baseline and 169 (5.6%) had incident alpha-gal sensitization (defined as subjects who sero-converted or had levels increase from baseline to follow-up). 6.6% of males versus 3.3% of females were sensitized at baseline, p=0.004. Adjusted for age, race and home state the odds ratio for sensitization was 1.8 in males (95%CI 1.1-3.0). Incident alpha-gal IgE was higher in males (6.4%) than females (2.4%), p<0.001. Adjusted for age, race and military branch the odds ratio for incident alpha-gal was 1.7 in males (95%CI 1.0-3.3). Using a nested control cohort (n=169) matched for age, sex, race and geography, incident alpha-gal subjects trended toward a lower frequency of B/AB blood types (12% vs 16%), but this was not significant (p=0.28). Conclusions: Alpha-gal sensitization is significantly associated with male sex, but not ABO-blood group status. |
Journal of Allergy and Clinical Immunology. 2023 Feb 1;151(2):AB93. | Epidemiology, military, blood type, prevalence, occupational medicine |
| Ailsworth S, Workman L, Susi A, Platts-Mills T, Nylund C, Wilson J. | 2024 | Is High-level Total IgE a Risk Factor for Alpha-gal Sensitization or a Consequence of Tick Bites?. |
Journal of Allergy and Clinical Immunology. 2024 Feb 1;153(2):AB46. | total IgE; risk factor; atopy; tick antigens; |
| Ailsworth SM, Susi A, Workman LJ, Ji YS, Patel J, Nelson MR, Platts-Mills TA, Nylund CM, Wilson JM | 2023 | Alpha-gal IgE Prevalence Patterns in the United States: An Investigation of 3000 Military Recruits. Background: IgE to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) is an important cause of allergic reactions to mammalian meat. The “alpha-gal syndrome” (AGS) is strongly associated with preceding history of tick bites and in the US is most commonly reported in parts of the southeast, but there has been limited investigation into national alpha-gal sensitization patterns and the relevance of other risk factors. Objective: Systematically investigate alpha-gal IgE prevalence, regional patterns and risk factors. Methods: Alpha-gal IgE was measured by ImmunoCAP in biobanked serum samples collected from 3000 service members who presented for intake to one of 10 military bases in the central/eastern US. Alpha-gal IgE sensitization (cut-off 0.1 IU/mL) was related to home of record at enlistment. Results: Of the cohort, 2456 subjects were male (81.9%), median age was 19 years (IQR 18-22) and alpha-gal IgE was detected in 179 (6.0%). Home of record spanned all 50 states, with a median of 36 recruits per state (range 3-261). The highest prevalence rates were in Arkansas (39%), Oklahoma (35%) and Missouri (29%), with several other southeastern states >10%. Granular mapping revealed sensitization patterns that closely mimicked county-level Amblyomma americanum reports and Ehrlichia chaffeensis infections. Sensitization was associated with male sex, rural residence and White race in univariate and multivariable models. Conclusions: In this systematic survey, prevalence of alpha-gal IgE among incoming military personnel was 6.0%. There were significant regional differences, with an overall pattern consistent with the known range of the lone star tick (A. americanum) and highest frequency in an area including Arkansas, Oklahoma and Missouri. |
The Journal of Allergy and Clinical Immunology: In Practice. | military; prevalence; epidemiology; geography; distribution; race; ethnicity; gender; |
| Airaksinen L, Suojalehto H, Lindström I, Sund J, Pallasaho P, Puustinen A. | 2022 | Characterization of relevant bovine dander allergen components. |
J Investig Allergol Clin Immunol. 2024;34(1):1. | Finland; occupational allergy; cattle farmer; cows |
| Aiuto B, Cirrincione S, Giuffrida MG, Cavallarin L, Portesi C, Rossi AM, Borreani G, Rolla G, Geuna M, Nicola S, Quinternetto A. | 2024 | 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 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. |
Molecular Nutrition & Food Research.:2300796. | |
| Aiuto B, Cirrincione S, Gosso E, Brussino L, Cavallarin L, Giuffrida MG, Rossi AM, Portesi C, Lamberti C. | 2024 | Study of α-gal glycosylation of cow's milk proteins and allergological implications. |
InALLERGY 2023 Dec 1 (Vol. 78, pp. 60-61). 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY. | milk; dairy; protein |
| Akarsu A, Soyer O, Sekerel BE. | 2020 | Hypersensitivity Reactions to Biologicals: from Bench to Bedside. Purpose of Review: Biologic agents are new treatment options for chronic inflammatory diseases and cancers. As a result of their unique mechanism of action, they are more effective and less toxic treatment option and their clinical usage is increasing. While they are more commonly used, various adverse effects have been observed including life-threatening ones, including anaphylaxis. The aim of this review is to distinguish the anaphylaxis from other hypersensitivity reactions (HSR) and provide a management algorithm for the anaphylactic reactions induced by biological agents. Recent Findings: Many case reports and series have been published regarding anaphylaxis and other hypersensitivity reactions (concerning cytokine release syndrome, acute infusion–related reactions) due to biologic agents. Although acute treatment of HSR varies according to the clinical presentation, desensitization with the drug is the major management option for subsequent administrations in the case of anaphylactic reactions. . Summary: Anaphylaxis and other immediate onset hypersensitivity reactions are occasionally difficult to differentiate from each other, and mixed-type reactions may be observed. Immediate management of anaphylaxis includes discontinuation of infusion, immediate administration of adrenaline, antihistamines, corticosteroids, and other treatment options depending on the symptoms. After 30–120 min of the reaction, a blood sample for serum tryptase levels should be obtained and after 4–6 weeks skin testing with the culprit drug should be performed for decision of long-term management via either graded challenge or desensitization. |
Current Treatment Options in Allergy. 2020 Jan 18:1-3. | review article; biologic; biological agent; mAb; monoclonal antibody; pharmacy; pharmaceutical |
| Akella K, Patel H, Wai J, Roppelt H, Capone D. | 2017 | Alpha Gal-Induced Anaphylaxis to Herpes Zoster Vaccination. INTRODUCTION: Reported incidence of tick borne illness has progressively risen over the last decade. Galactose-alpha-1,3- galactose (alpha gal) allergy is a novel presentation of a tick borne illness induced by the Lone Star Tick, which is a well known vector for ehrlichiosis, tularemia, and Southern Tick-associated Rash Illness (STARI). Individuals with tick borne illnesses in the Lone Star Tick distribution of southern, midwestern and northeastern states are at greater risk for developing this condition. Three major hypotheses exist to describe how ticks might induce an IgE response through transmission of alpha gal: 1) alpha gal may be a component of tick saliva, 2) alpha gal may be residual from prior blood meal, and 3) alpha gal may be transmitted through commensal organism transmission. Clinical presentation of alpha gal allergy includes gastrointestinal symptoms, itching and urticaria, and delayed anaphylaxis. There has been one prior report of alpha gal induced anaphylaxis after administration of herpes zoster vaccination in the literature. We describe a second, unique presentation of this allergic condition observed at our institution. CASE PRESENTATION: A 73 year old female with a past medical history of hypertension, chronic hepatitis C, and alpha gal allergy presented to our Emergency Department for near syncope after epinephrine administration for upper lip, mouth and tongue swelling experienced 45 minutes after obtaining her herpes zoster vaccination. Review of the vaccination contents revealed use of porcine gelatin - a meat product felt to have induced an IgE response in the setting of alpha gal allergy. The patient was admitted, managed with intravenous fluids, and discharged the following morning. DISCUSSION: To increase physician awareness of alpha gal allergy and increased incidence in populations exposed to tick-borne diseases. We suggest avoiding administering the herpes zoster vaccine in patients with a history of a tick borne illness. CONCLUSIONS: Alpha gal allergy is a relatively novel presentation of tick borne illness induced by the Lone Star Tick - commonly found in the southern, midwest and northeastern United States. We report an unusual case of alpha gal allergy with anaphylaxis induced by herpes zoster vaccination due to use of porcine gelatin. |
Chest. 2017 Oct 1;152(4):A6. | pharmacy; vaccination; vaccine; herpes zoster; primary care; management |
| Altman MO, Gagneux P. | 2019 | Absence of Neu5Gc and presence of anti-Neu5Gc antibodies in humans—an evolutionary perspective. The glycocalyx of human cells differs from that of many other mammals by the lack of the sialic acid N-glycolylneuraminic acid (Neu5Gc) and increased abundance of its precursor N-acetylneuraminic acid (Neu5Ac). Most humans also have circulating antibodies specifically targeting the non-human sialic acid Neu5Gc. Recently, several additional mammalian species have been found to also lack Neu5Gc. In all cases, loss-of-function mutations in the gene encoding the sialic acid-modifying enzyme CMAH are responsible for the drastic change in these species. Unlike other glycan antigens, Neu5Gc apparently cannot be produced by microbes, raising the question about the origin of these antibodies in humans. Dietary exposure and presentation on bacteria coating themselves with Neu5Gc from the diet are distinct possibilities. However, the majority of the non-human species that lack Neu5Gc do not consume diets rich in Neu5Gc, making it unlikely that they will have been immunized against this sialic acid. A notable exception are mustelids (ferrets, martens and their relatives) known for preying on various small mammal species rich in Neu5Gc. No studies exist on levels of anti-Neu5Gc antibodies in non-human species. Evolutionary scenarios for the repeated, independent fixation of CMAH loss-of-function mutations at various time points in the past include strong selection by parasites, especially enveloped viruses, stochastic effects of genetic drift, and directional selection via female immunity to paternal Neu5Gc. Convergent evolution of losses of the vertebrate-specific self-glycan Neu5Gc are puzzling and may represent a prominent way in which glycans become agents of evolutionary change in their own right. Such change may include the reconfiguration of innate immune lectins that use self-sialic acids as recognition patterns. |
Frontiers in immunology. 2019 Apr 30;10:789. | glycan antigen; xenoglycan; sialic acid; Neu5Gc; Neu5Ac; carbohydrate; evolution |
| Altmann F. | 2016 | Coping with cross-reactive carbohydrate determinants in allergy diagnosis. A relevant proportion of allergy diagnosis is accomplished by in vitro determination of specific immunglobulin E (sIgE) to extracts from suspected allergens. Such extracts inevitably contain glycoproteins, which may react with patients’ IgE. In the case of plant and insect allergens, the relevant epitope structure is an alpha-1,3-fucose on the Asn-linked sugar residue of so-called N-glycans. Due to their wide distribution, N-glycans carrying this epitope are known as “cross-reactive carbohydrate determinant(s)” (CCD[s]). About 15 years of awareness allow the conclusion that anti-CCD IgE does not cause noticeable clinical symptoms. In consequence, diagnostic results arising from CCD reactivity must be rated as false positives. With up to 30 % of CCD reactive patients, this can be regarded as a serious problem. Another cross-reactive carbohydrate determinant became notorious as a potential cause of anaphylactic reactions to a recombinant glycoprotein drug carrying alpha-1,3-galactose. This galactose-containing determinant (GalCD, galactose containing cross-reactive carbohydrate determinant) was supposed as a trigger for delayed allergic reactions to red meat in several cases. Thus, alpha-1,3-galactose may have clinical relevance in certain cases – possibly as a result of tick bites. Often, however, GalCDs probably cause false-positive results with milk and meat extracts. No clear evidence for the role of other non-human carbohydrate structures such as N-glycolylneuraminic acid as CCD has been presented so far. Remedies for sIgE based in vitro diagnosis come in the form of non-glycosylated recombinant allergen components or of specific CCD inhibitors. The high potential of recombinant allergens is optimally realized in the context of component resolved diagnosis using allergen arrays with more than 100 components, whereas CCD inhibitors increase the specificity of conventional extract-based diagnosis. Reagents for the detection and inhibition of CCDs from plants and insects have been developed, whereas tools for GalCDs of milk and meat lag behind. |
Allergo journal international. 2016 Jun 1;25(4):98-105. | cross-reactive carbohydrate determinant; CCD |
| Altmann F. | 2007 | The role of protein glycosylation in allergy. The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are the most abundant environmental immune determinants. They are the structural basis of what is known as cross-reactive carbohydrate determinants (CCDs). Despite some structural variation, the two main motifs are the xylose and the core-3-linked fucose, which form the essential part of two independent epitopes. Plants contain both epitopes, insect glycoproteins only fucose. These epitopes and other fucosylated determinants are also found in helminth parasites where they exert remarkable immunomodulatory effects. About 20% or more of allergic patients generate specific anti-glycan IgE, which is often accompanied by IgG. Even though antibody-binding glycoproteins are widespread in pollens, foods and insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus can be rated as clinical irrelevant allergen. Low binding affinity between IgE and plant N-glycans now drops out as a plausible explanation for the benign nature of CCDs. This rather may result from blocking antibodies induced by an incidental ‘immune therapy’ (‘glyco-specific immune therapy’) exerted by everyday contact with plant materials, e.g. fruits or vegetables. The need to detect and suppress anti-CCD IgE without interference from peptide epitopes can be best met by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single β-arabinofuranosyl residues) has been identified as a new IgE-binding carbohydrate epitope in the major mugwort allergen. However, currently the occurrence of this O-glycan determinant appears to be rather restricted. |
International archives of allergy and immunology. 2007;142(2):99-115. | Glycan antigen; xenoglycan; sialic acid; Neu5Gc; Neu5Ac; carbohydrate |
| Altomari C, Candido K, Uchi J, Shah S. | 2025 | Role of Omalizumab in Alpha-gal Syndrome Based on Social Media Reports. |
Journal of Allergy and Clinical Immunology. 2025 Feb 1;155(2):AB103. | |
| Altrich ML, Blum SP, Foster SM. | 2015 | Delayed Anaphylaxis to Mammalian Meat: A Fascinating Disease and Captivating Story. Delayed anaphylaxis to mammalian meat is a newly recognized IgE-mediated syndrome associated with Lone Star tick bites. IgE-mediated anaphylaxis classically occurs within one hour of exposure to the allergen, which is typically a protein epitope. However, in this disease, circulating antibodies to a carbohydrate, alpha-gal (galactose-alpha-1,3-galactose), stimulate the anaphylactic cascade with hives, diarrhea, abdominal cramps, respiratory distress and anaphylactic shock developing after ingestion of beef, pork or lamb meat. The delayed onset of symptoms three to six hours after ingestion of meat is unique. Recognition and understanding of this disease is important for treating and educating patients with suggestive symptoms. Avoidance of red meat is the recommended therapy. |
Journal of Allergy and Clinical Immunology. 2015 Feb 1;135(2):AB37. | North America; United States; prevalence |
| Altshuler E, Krikpatrick J, Aryan M, Miralles F. | 2021 | Mammalian meat allergy emerges after tick bite: the alpha-gal syndrome. Alpha-gal syndrome (AGS) is a hypersensitivity reaction to mammalian meat that develops after tick bite exposure. AGS was first described in 2009 and testing for the allergy has become available in the last decade. We report the case of a 56-year-old farmer with a history of frequent lone star tick bites who presented with a 7-year history of diffuse urticaria occurring hours after eating red meat. AGS is likely underdiagnosed because of the unusual presentation of the allergy, historic lack of available testing, and deficiency of physician knowledge about the condition. Recognition of AGS is important both to help alleviate symptom burden and to avoid iatrogenesis. Patients with AGS should not receive products containing mammalian products, such as cat-gut suture, porcine-derived heart valves, and bovine-derived vaccines. Patients with AGS may present in a variety of clinical environments and physicians of all kinds should be able to recognise the symptoms. |
BMJ Case Reports CP. 2021 Nov 1;14(11):e245488. | Florida |
| Alvarez-Perea A, Caralli ME, Zubeldia JM, Baeza ML. | 2014 | Pork-cat syndrome as a cause of occupational asthma. We report the case of a 30-year-old woman with a family history of atopy. At the age of 13, soon after receiving a cat, she began to experience perennial ocular and nasal symptoms, as well as cough, wheeze, and dyspnea, all of which worsened in spring. At age 14, she was diagnosed with allergic rhinoconjunctivitis and mild intermittent asthma caused by pollen and dander. Her allergy improved when the cat was removed, and symptoms remained limited to mild rhinoconjunctivitis in springtime, although she still had mild asthma throughout the year when practicing sports. When she was 20, she started working at a grocery store selling cured meats. One of her duties was to cut pork bones (cured and cooked ham). From that point, her rhinoconjunctivitis worsened and her asthma attacks resumed. These manifestations were exacerbated at her workplace, especially when she had to cut pork bones. Her asthma continued to deteriorate, and she experienced 3-4 exacerbations per year that forced her to be absent from work. She frequently needed aerosol therapy after work, although she felt better on days off work and was almost asymptomatic during vacations. In 2010-2011, she was admitted to hospital on 4 occasions, forcing her to miss work for 1-2 months each time. Her asthma was controlled with oral corticosteroids. |
J Investig Allergol Clin Immunol. 2014 Jan 1;24(3):192-211. | airborne reactions; pork-cat syndrome; occupational medicine |
| Amoah AS, Asuming-Brempong EK, Obeng BB, Versteeg SA, Larbi IA, Aryeetey Y, Platts-Mills TA, Mari A, Brzezicka K, Gyan BA, Mutocheluh M. | 2018 | Identification of dominant anti-glycan IgE responses in school children by glycan microarray. Letter to the editor In helminth-endemic areas, elevated levels of cross-reactive IgE to environmental and food allergens are often seen that do not translate into positive skin prick test results or allergy symptoms. 1 Among Ghanaian children, such cross-reactivity was shown to be associated with Schistosoma haematobium infection and dominated by high IgE against cross-reactive carbohydrate determinants (CCDs). 2 The specific carbohydrate motifs involved in this IgE recognition were not determined. |
Journal of Allergy and Clinical Immunology. 2018 Mar 1;141(3):1130-3. | |
| Andrade AL, Riccetto AG, Vilela MM, de Oliveira DN, Catharino RR, Nolasco da Silva MT. | 2018 | Anaphylactic reaction to galactose‐derived oligosaccharide residues from lactose used as a drug excipient. Inhaled steroids are currently the most widely used and recommended medicines for the management of persistent asthma because of their high local and anti-inflammatory efficacy.1 There are three main presentations of the drug: aerosol spray (hydrofluoroalkane – HFA - as a propellant), liquid solution and dry powder inhaler. Dry powder devices are often preferred over HFA sprays in patients over 6 years of age, both for environmental issues and for the intrinsic advantages of the technique, such as ease of use and greater uptake and metabolism of the drug.1,2 This article is protected by copyright. All rights reserved. |
Pediatric Allergy and Immunology. 2018 Mar 1;29(2):207-10. | |
| Anemüller W, Mohr M, Brans R, Homann A, Jappe U. | 2018 | Alpha-Gal-assoziierte verzögerte Anaphylaxie gegen rotes Fleisch als Berufskrankheit. Bei einem 30-jährigen Koch mit rezidivierenden verzögerten Angioödemen konnte anamnestisch und laborexperimentell als Ursache die Sensibilisierung gegen das Kohlenhydratepitop Galactose-alpha-(1,3)-Galactose (alpha-Gal) aufgedeckt werden. Mit der Diagnose einer verzögerten Anaphylaxie bei Sensibilisierung gegen alpha-Gal erfolgte aufgrund des beruflichen Bezuges die Meldung an die Berufsgenossenschaft mittels Hautarztbericht BK 5101. Hierauf wurde dem Patienten fristlos gekündigt. Als Konsequenz zeigten wir eine Berufskrankheit an. Diese Kasuistik stellt die Bedeutung der unterdiagnostizierten, potenziell lebensbedrohlichen Allergie gegen das Disaccharid alpha-Gal des roten Fleisches als Berufskrankheit dar. English translation: Alpha-gal associated delayed red meat anaphylaxis as an occupational disease In a 30-year-old chef with recurrent delayed angioedema history as well as the experimental detection of IgE antibodies to galactose-alpha (1,3) -galactose (alpha-gal) pointed to alpha gal as the causative agent. The diagnosis, therefore, was delayed by anaphylaxis due to alpha-gal. Because of the potential relationship to his profession, we have submitted a dermatologist's report BK 5101 to the liability and insurance association, whereupon his contract of employment without notice. As a result, we reported an occupational disease. This case demonstrates underdiagnosed, potential life-threatening allergy to the disaccharide alpha gal in red meat as to occupational disease. |
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2018 Oct;69(10):848-52. | Anemuller; occupational medicine; chef |
| Angiolillo A, Gandaglia A, Arcaro A, Carpi A, Gentile F, Naso F, Di Costanzo A. | 2021 | Altered Blood Levels of Anti-Gal Antibodies in Alzheimer’s Disease: A New Clue to Pathogenesis?. Alzheimer’s disease is a neurodegenerative disorder whose pathological mechanisms, despite recent advances, are not fully understood. However, the deposition of beta amyloid -peptide and neuroinflammation, which is probably aggravated by dysbiotic microbiota, seem to play a key role. Anti-Gal are the most abundant xenoreactive natural antibodies. They are supposed to stem from immunization against the gut microbiota and have been implicated in the pathogenesis of several diseases, including multiple sclerosis. These antibodies target the alpha-Gal epitope, expressed on the terminal sugar units of glycoprotein or glycolipid of all mammals except apes, Old World monkeys and humans. The alpha-Gal is constitutively expressed in several bacteria constituting the brain microbiota, and alpha-Gal-like epitopes have been detected in gray matter, amyloid plaque, neurofibrillary tangles and corpora amylacea of the human brain, suggesting a potential link between anti-Gal and Alzheimer’s disease etiopathogenesis. For the first time, our study searched for possible alterations of anti-Gal immunoglobulin levels in Alzheimer’s disease patients. IgG and IgM blood levels were significantly lower, and IgA significantly higher in patients than in healthy subjects. These results suggest that such immunoglobulins might be implicated in Alzheimer’s disease pathogenesis and open new scenarios in the research for new biomarkers and therapeutic strategies. |
Life. 2021 Jun;11(6):538. | Brain; Alzheimer's; anti-gal; autoimmune |
| Ankersmit HJ, Copic D, Simader E. | 2017 | When meat allergy meets cardiac surgery: A driver for humanized bioprosthesis. Virginia cardiothoracic surgeons, recently described 2 patients who underwent implantation of a bioprosthetic aortic valve and postoperatively developed a meat allergy associated with a gal-specific IgE immune response. Both patients developed premature degeneration of their bioprosthesis that required reoperation and implantation of a mechanical valve in the aortic position.10 What can we learn as academic surgeons from this scientific story? (1) Big Pharma has not reacted to academic work to provide more durable gal-deficient bioprosthesis. Cardiac surgeons and cardiologists are continuing to implant valves that are known to induce a systemic immune response, leading to precocious degeneration. Furthermore, the uncritical lowering of age limits for biovalve replacement has severe consequences.11,12 (2) Academic research pertaining to the alpha-gal immune response in cardiac surgery is rather meek: A PubMed search in November 2016 with the key words ‘‘alpha-gal’’ and ‘‘valve’’ brought up only 40 citations. (3) Only the very avant-garde centers, such as the Hannover and Seoul Group, are trying to tackle this important question by means of detergent-based decellularization procedures13,14 or by using alpha-galactosidase.15 Tissueengineering research is ongoing in most academic centers of relevance, but commercial producers must instigate the manufacture of such ‘‘humanized’’ bioprostheses with potentially longer life spans. The first successful endeavors in that direction have been reported.16 Allergy and cardiac surgery do not particularly fit together, but in my opinion these ‘‘case insights’’ from patients with meat allergy with valve degeneration will lead to commercially available gal-deficient bioprostheses for future generations of patients with valve disease. Another speculation is that regulatory affairs in the European Union or the Food and Drug Administration in the United States will force the industry to provide such valves, and then ignorance will be overcome. The valve industry takes pride in being innovative at annual cardiac surgery meetings. Will we wait for another decade for action? |
The Journal of thoracic and cardiovascular surgery. 2017 Oct 1;154(4):1326-7. | cardiac surgery; cardiothoracic surgery; bioprosthetic heart valve |
| Apari P, Földvári G | 2022 | Tick bite induced α‐gal syndrome highlights anticancer effect of allergy. Tick bite induced α-gal syndrome (AGS) following consumption of mammalian meat is a recently described intriguing disease occurring worldwide. Here we argue that AGS and delayed allergy in general is an adaptive defence method against cancer. Our hypothesis synthesizes two lines of supporting evidence. First, allergy has been shown to have direct anti-cancer effects with unknown mechanism. Second, eating processed meat was shown to be linked to developing cancer. Humans lost their genes encoding molecules α-gal 30 MYA and Neu5Gc 2 MYA, the latter co-occurring with the start of using fire. These molecules are acquired from external sources, as tick bite for α-gal and mammalian meat for Neu5Gc, the latter accumulating in tumors. The resulting specific delayed allergic response is a molecular adaptation to fight cancer. By further testing and applying our hypothesis, new avenues in cancer research and therapy will open that might save lives and decrease human suffering. |
BioEssays. 2022 Jan;44(1):2100142. | cancer |
| Apostolovic D, Bigdeli N, Starkhammar M, van Hage M. | 2019 | Red meat allergic patients have specific TH2 derived cellular and humoral responses against Ixodes ricinus tick proteins supporting the link to alpha-gal allergy. | ALLERGY. 2019 Aug 1; 4: 155-156. | Europe; Sweden; vector; Ixodes ricinus |
| Apostolovic D, Grundström J, Kiewiet MB, Perusko M, Hamsten C, Starkhammar MH, Paulie S, van Hage M. | 2023 | Th2-skewed T cells correlate with B cell response to α-Gal and tick antigens in α-Gal syndrome. Tick bites have been shown to transmit a novel form of severe food allergy, the galactose-α-1,3-galactose (α-Gal) syndrome (AGS). Cellular responses to α-Gal in AGS patients have to date not been thoroughly scrutinized. Therefore, we investigated T and B cell proliferation, activation and cytokine profiles in response to tick protein extract (TE) and α-Gal-free TE in AGS patients and healthy controls. T and B cells from both patients and controls proliferated in response to TE, but significantly more in the patients. B cell proliferation, but not T cell proliferation, in AGS patients was reduced by removing α-Gal from the TE. In addition, TE induced a clear Th2 cytokine profile in AGS patients. Expression of CD23 by B cells correlated only to T cell proliferation. However, both B cell proliferation and CD23 expression were reduced when CD40L and IL-4 were blocked. A large proportion of the IgG1 and IgE antibodies binding TE in AGS patients were directed against the α-Gal epitope. We have for the first time investigated T and B cell responses to α-Gal carrying tick proteins in AGS patients, which will be essential for the understanding of the immune response against an allergenic carbohydrate transmitted by ticks. |
The Journal of Clinical Investigation. 2023 Jan 26. | cellular mechanisms; B cells; T cells |
| Apostolovic D, Krstic M, Mihailovic J, Starkhammar M, Velickovic TC, Hamsten C, van Hage M. | 2017 | Peptidomics of an in vitro digested a-Gal carrying protein revealed IgE-reactive peptides. The mammalian carbohydrate galactose-α1,3-galactose (α-Gal) causes a novel form of food allergy, red meat allergy, where patients experience severe allergic reactions several hours after red meat consumption. Here we explored gastric digestion of α-Gal glycoproteins using an in vitro model. Bovine thyroglobulin (BTG), a typical α-Gal carrying glycoprotein, was digested with pepsin. The resulting peptides were characterized by SDS PAGE, immunoblot and ImmunoCAP using sera from 20 red meat allergic patients. During pepsinolysis of BTG, a wide range of peptide bands was observed of which 14 to 17 kDa peptides remained stable throughout the gastric phase. The presence of the α-Gal epitope on the obtained peptides was demonstrated by an anti-α-Gal antibody and IgE from red meat allergic patients. The α-Gal digests were able to inhibit up to 86% of IgE reactivity to BTG. Importantly, basophil activation test demonstrated that the allergenic activity of BTG was retained after digestion in all four tested patients. Mass spectrometry-based peptidomics revealed that these peptides represent mostly internal and C-terminal parts of the protein, where the most potent IgE-binding α-Gal residues were identified at Asn1756, Asn1850 and Asn2231. Thus allergenic α-Gal epitopes are stable to pepsinolysis, reinforcing their role as clinically relevant food allergens. |
Scientific reports. 2017 Jul 12;7(1):1-0. | proteins; peptides; digestion; stability Sweden; Europe |
| Apostolovic D, Mihailovic J, Commins SP, Wijnveld M, Kazimirova M, Starkhammar M, Stockinger H, Platts-Mills TA, Cirkovic VT, Hamsten C, van Hage M. | 2020 | Allergenomics of the tick Ixodes ricinus reveals important alpha-Gal-carrying IgE-binding proteins in red meat allergy. Letter to the editor. |
Allergy. 2020 Jan;75(1):217. | Europe; Sweden; vectors; Ixodes ricinus; |
| Apostolovic D, Rodrigues R, Thomas P, Starkhammar M, Hamsten C, van Hage M. | 2018 | Immunoprofile of α‐Gal‐ and B‐antigen‐specific responses differentiates red meat‐allergic patients from healthy individuals. Background: The galactose--1,3-galactose (-Gal) epitope is involved in red meat allergy. As -Gal is structurally similar to the blood group B-antigen, we explored the relationship between the immune responses to -Gal- and the B-antigen in red meat-allergic patients compared to healthy A/O or B blood donors. Methods: Sera from 51 red meat-allergic patients IgE-positive to -Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B) were included. -Gal- and B-antigen-specific IgE (ImmunoCAP) and IgG/IgG (1-4) (ELISA) responses were determined. Basophil activation tests were performed. Results: Fifteen healthy donors were IgE positive to -Gal, of which 3 had blood group B. The allergic patients had significantly higher -Gal IgE levels compared to the healthy donors. The majority of the allergic patients, but none of the healthy donors, had IgE against the B-antigen. Inhibition studies revealed cross-reactivity between -Gal and the B-antigen. The biological activity of the B-antigen was confirmed by basophil activation tests. Anti--Gal IgG (1) and IgG (4) levels were significantly higher in the patients compared to the healthy donors. Moreover, the IgG response to the B-antigen was comparable between the allergic patients and healthy A/O donors. Conclusion: Red meat-allergic patients showed significantly higher -Gal IgE, IgG (1), and IgG (4) levels, reflecting a Th2 response, compared to healthy blood donors. Blood group B donors had significantly reduced antibody responses to -Gal, due to similarities with the B-antigen, resulting in a lower risk of sensitization to -Gal and development of red meat allergy. |
Allergy. 2018 Jul;73(7):1525-31. | Europe; Sweden; Blood group |
| Apostolovic D, Tran TA, Hamsten C, Starkhammar M, Cirkovic Velickovic T, van Hage M. | 2014 | Immunoproteomics of processed beef proteins reveal novel galactose-alpha-1,3-galactose-containing allergens. BACKGROUND: Red meat allergy presents a novel form of food allergy with severe delayed allergic reactions where IgE antibodies are directed against the carbohydrate alpha-Gal epitope. Food preparation and processing can influence the allergenicity of proteins. The aim of this study was to characterize the proteomic profile of different beef preparations and to investigate their alpha-Gal reactivity and potential allergenicity. METHODS: Extracts from raw, boiled, fried, and medium rare prepared beef were assessed by 2D PAGE for the comparison of protein profiles. IgE-binding proteins were identified using immunoblot-coupled proteomic analysis using sera from red meat-allergic patients. Presence of the alpha-Gal epitope was verified using anti-alpha-Gal antibody and IgE inhibition immunoblot with alpha-Gal. RESULTS: Multiple IgE-binding proteins were detected in the different beef preparations, many of which were also recognized by the anti-alpha-Gal antibody. Protein spots reacting with IgE in patient sera were analyzed by MS/MS, resulting in identification of 18 proteins with high identification scores. Seven of the 18 beef allergens identified using meat-allergic patient sera were also recognized by the anti-alpha-Gal monoclonal antibody, and four of them were stabile to thermal treatment. Furthermore, a dose-dependent inhibition of red meat-allergic patients' IgE to beef by alpha-Gal was demonstrated. CONCLUSIONS: We show that the alpha-Gal epitope is commonly present in IgE-reactive beef proteins recognized by meat-allergic patients. Seven novel alpha-Gal-containing IgE-binding proteins were identified, of which four were stable to heat treatment. Thus, the allergenicity of red meat proteins is preserved even upon different thermal cooking. |
Allergy. 2014 Oct;69(10):1308-15. | Europe; Sweden; proteins; beef; cooking; thermal stability; |
| Apostolovic D, Tran TA, Starkhammar M, Sánchez-Vidaurre S, Hamsten C, Van Hage M. | 2016 | The red meat allergy syndrome in Sweden. In the last decade, a novel type of food allergy presenting with severe allergic reactions several hours after consumption of red meat has been recognized. The allergic responses are due to IgE antibodies directed against the carbohydrate epitope galactose-α-1,3-galactose (α-Gal) found in mammalian meat. This review presents the red meat allergy syndrome in Sweden, discusses the features of the immune response to carbohydrates, and highlights the presence of heat stable α-Gal-containing proteins in meat. The number of diagnosed red meat allergy cases in Sweden has increased significantly over the past few years. All patients have been tick bitten. Our recent work has shown that α-Gal is present in the European tick Ixodes ricinus (I. ricinus), thus potentially explaining the strong association between anti-α-Gal IgE and tick bites, with development of red meat allergy as a secondary phenomenon. Further studies using immunoproteomics have identified novel α-Gal-containing meat proteins that bound IgE from red meat allergic patients. Four of these proteins were stable to thermal processing pointing to the fact that the allergenicity of red meat proteins is preserved in cooked meat. In keeping with the fact that the α-Gal epitope is structurally related to the blood group B antigen, a positive association with the B-negative blood groups among our red meat allergic patients was noted. A selective IgE reactivity to the pure carbohydrate moiety was observed when investigating the specificity of the α-Gal immune response. IgE from red meat allergic patients does not recognize the other major mammalian carbohydrate, N-glycolylneuraminic acid (Neu5Gc), also present in high amounts in red meat. Furthermore, neither common cross-reactive carbohydrate determinants (CCDs) from plants nor venoms are targets of the IgE response in these patients. . Taken together, the α-Gal carbohydrate has shown to be a potentially clinically relevant allergen that should be taken into account in the diagnosis of food allergy. Many new findings in the field of red meat allergy have been obtained during the past years, but further efforts to understand the process of digestion, absorption, and delivery of α-Gal-containing molecules to the circulation are needed. |
Allergo Journal. 2016 Mar 1;25(2):29-34. | Europe; Sweden; Sanchez-Vidaurre; review article; Europe; Scandanavia; Sweden |
| Apostolovic D, Tran TA, Sánchez‐Vidaurre S, Cirkovic Velickovic T, Starkhammar M, Hamsten C, van Hage M. | 2015 | Red meat allergic patients have a selective IgE response to the α-Gal glycan. Galactose-alpha-1,3-galactose (alpha-Gal) is a mammalian carbohydrate with significance in a novel type of food allergy. Patients with IgE against alpha-Gal report severe allergic symptoms 3-6 h after consumption of red meat. We investigated whether IgE from red meat allergic patients recognizes other mammalian glycans than alpha-Gal or glycans from the plant kingdom and insects of importance in allergy. We found that none of the 24 red meat allergic patients investigated had an IgE antibody response against the other abundant mammalian glycan N-glycolylneuraminic acid or against cross-reactive carbohydrate determinants from plant or venom sources (nCup a 1, nArt v 1, and MUXF3). Deglycosylation of an alpha-Gal-containing protein, bovine thyroglobulin, significantly reduced the IgE response. In conclusion, we show that red meat allergic patients have a selective IgE response to the alpha-Gal glycan found in red meat. Other common glycans reactive in allergic disease are not targets of red meat allergic patients' IgE. |
Allergy. 2015 Nov;70(11):1497-500. | Europe; Sweden; Sanchez-Vidaurre; glycan; cross-reactive carbohydrate determinant; Neu5Gc; N-glycolylneuraminic acid |
| Araujo RN, Franco PF, Rodrigues H, Santos LC, McKay CS, Sanhueza CA, Brito CR, Azevedo MA, Venuto AP, Cowan PJ, Almeida IC, Finn MG, Marques MF. | 2016 | ** Amblyomma sculptum tick saliva: alpha-Gal identification, antibody response and possible association with red meat allergy in Brazil. The anaphylaxis response is frequently associated with food allergies, representing a significant public health hazard. Recently, exposure to tick bites and production of specific IgE against α-galactosyl (α-Gal)-containing epitopes has been correlated to red meat allergy. However, this association and the source of terminal, non-reducing α-Gal-containing epitopes have not previously been established in Brazil. Here, we employed the α-1,3-galactosyltransferase knockout mouse (α1,3-GalT-KO) model and bacteriophage Qβ-virus like particles (Qβ-VLPs) displaying Galα1,3Galβ1,4GlcNAc (Galα3LN) epitopes to investigate the presence of α-Gal-containing epitopes in the saliva of Amblyomma sculptum, a species of the Amblyomma cajennense complex, which represents the main tick that infests humans in Brazil. We confirmed that the α-1,3-galactosyltransferase knockout animals produce significant levels of anti-α-Gal antibodies against the Galα1,3Galβ1,4GlcNAc epitopes displayed on Qβ-virus like particles. The injection of A. sculptum saliva or exposure to feeding ticks was also found to induce both IgG and IgE anti-α-Gal antibodies in α-1,3-galactosyltransferase knockout mice, thus indicating the presence of α-Gal-containing epitopes in the tick saliva. The presence of α-Gal-containing epitopes was confirmed by ELISA and immunoblotting following removal of terminal α-Gal epitopes by α-galactosidase treatment. These results suggest for the first known time that bites from the A. sculptum tick may be associated with the unknown etiology of allergic reactions to red meat in Brazil. |
International journal for parasitology. 2016 Mar 1;46(3):213-20. | Latin America; Brazil; vectors; tick species; Amblyomma sculptum; tick saliva |
| Archer-Hartmann SA, Crispell G, Karim S, Dharmarajan G, Azadi P. | 2018 | Tick Bites and Hamburgers: N-Glycosylation analysis of saliva and salivary glands from the ticks responsible for Alpha-Gal Syndrome. | GLYCOBIOLOGY. 2018 Dec 1; 28(12):1080-1081. | vectors; tick saliva |
| Arkestål K, Sibanda E, Thors C, Troye-Blomberg M, Mduluza T, Valenta R, Grönlund H, van Hage M. | 2011 | Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α-1,3-galactose. BACKGROUND: The carbohydrate epitope galactose-alpha 1,3-galactose (alpha-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that alpha-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). OBJECTIVE: We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and alpha-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. METHODS: Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with alpha-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and alpha-Gal was analyzed by means of ELISA. RESULTS: Among the 47 parasite-infected patients, 85% had IgE antibodies against alpha-Gal (OD; median, 0.175; range, 0.102-1.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.103-1.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and alpha-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and alpha-Gal (P < .001). Among the group with cat allergy, only 5 patients had IgE to alpha-Gal, and nearly 75% (n = 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kU(A)/L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P < .05) but no correlation between CDE and Fel d 5 and alpha-Gal. CONCLUSION: IgE to alpha-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/allergy in parasite-infested areas. |
Journal of Allergy and Clinical Immunology. 2011 Apr 1;127(4):1024-8. | Arkestal Gronlund; Africa; Zimbabwe; cat allergy; non-tick vector; parasite; helminth; geohelminth; Ascaris lumbricoides; Ascaris lumbricoides; Necator americanus; hookworm; Ancylostoma duodenaleschistosome; schistosomiasis |
| Armentia A, Martin-Gil FJ, Pascual C, Martin-Esteban M, Callejo A, Martinez C | 2006 | Anisakis simplex allergy after eating chicken meat. Background: Allergic reactions to food can be produced by contaminants that induce sensitization. Among these, Anisakis simplex can cause seafood infestation, and allergic symptoms (urticaria–angioedema, anaphylaxis, and asthma) can follow the eating or handling of affected fish. Although seafood is the principal source of human infections by this parasite, we have found allergic symptoms in 8 patients previously diagnosed as having A simplex sensitization after they ate chicken meat. Chicken feed usually has a high proportion of fishmeal, which might possibly be contaminated by this nematode. Objective: The aim of our study was to determine whether parasite proteins present in chicken meat could be responsible for the symptoms reported by these subjects. Methods: We carried out in vivo tests (prick, bronchial challenge, and double-blind placebo-controlled challenge with meat chicken) in these 8 patients. We performed immunoblotting using the sera from the 8 patients and controls in order to detect A simplex sensitization. We also investigated the presence of A simplex proteins in sera from chickens fed with fishmeal and in other sera from chickens fed only with cereals. We excluded sensitization to other chicken nematodes by serologic methods. Results: All 8 patients presented positive prick and challenges to A simplex. When we used serum from chickens fed with fishmeal as the antigen in blotting, patients 3, 4, 5, 6, 7, and 8 recognized a band of 16 kd, also obtained when using pools of fish–shellfish and A simplex larva. No detection was observed with sera from chickens fed with only cereals. Conclusion: We provide evidence, based on in vivo and in vitro tests, that subjects highly sensitized to A simplex can detect the presence of Anisakis species allergens in chicken meat. |
Journal of Investigational Allergology and Clinical Immunology. 2006 Jan 1;16(4):258. | Chicken diet |
| Armstrong P, Binder A, Amelio C, Kersh G, Biggerstaff B, Beard C, Petersen L, Commins S. | 2019 | Descriptive Epidemiology of Patients Diagnosed with Alpha-gal Allergy—2010–2019. Rationale: Alpha-gal allergy is an immunoglobulin E (IgE) mediated allergy to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate found in mammalian meat. Clinical presentation ranges from hives to anaphylaxis, and episodes typically occur 3–6 hours after ingestion of meat. Exposure to the Lone Star tick (Amblyomma americanum) has been implicated as the primary risk factor for developing alpha-gal allergy. Methods: We performed a retrospective, descriptive analysis of randomly selected patients with alpha-gal allergy, with at least one positive (IgE ≥ 0.1) test, who presented for care during 3/2010–3/2019. Data were collected through medical chart review and analyzed using SAS v9.4 (Cary, NC). Results: Of 100 patients, median age at onset was 53 years (IQR 42-60), 56% were female, and 95% reported Caucasian race. Pre-existing food allergies were rare. Nearly all (86, 97%) reported history of tick or chigger bite prior to onset. On average, patients experienced 3 episodes before diagnosis. Common symptoms included hives (63%), abdominal pain (39%), and nausea/vomiting (33%). The most commonly reported triggers were beef (42%), dairy (33%), pork (26%) and red meat (26%). Conclusions: Alpha-gal allergy occurs predominantly in Caucasian adults. Previously noted trends, such as report of tick bite, and lack of prior food allergies were also seen in this cohort. Hives is the most commonly reported symptom; however, gastrointestinal involvement remains prominent. Dairy was reported as a trigger in a larger proportion of patients than has been seen in other studies. Continued understanding of this condition is important for detection and clinical management. |
Journal of Allergy and Clinical Immunology. 2020 Feb 1;145(2):AB145. | CDC; epidemiology; symptoms; triggers; dairy; gastrointestinal; GI |
| Arnold DF, Misbah SA. | 2008 | Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. TO THE EDITOR: Chung and colleagues (March 13 issue)1 found IgE antibodies to galactose-α-1,3-galactose in pretreatment serum samples from 17 of 25 patients who had hypersensitivity reactions to cetuximab, whereas IgE antibodies were found in only 1 of 51 patients who did not have a hypersensitivity reaction. If, as suggested, the presence of such antibodies in pretreatment samples is predictive of anaphylaxis, pretreatment testing would help in minimizing the risk of anaphylaxis associated with cetuximab. It would be important to know whether skin testing was done in the study patients, and if so, whether the results were concordant with the presence of IgE antibodies to cetuximab. |
The New England journal of medicine. 2008 Jun 1;358(25):2735-author. | biologics; biological agents; monoclonal antibody; mAb; cetuximab; |
| Arroyo A, Tourangeau, L. | 2015 | Regional anaphylaxis: Not so regional? A case of IgE antibodies to Alpha-Gal after tick bite in California. | ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY. 2015 Nov 1; 115(5):A71-A71. | geography; distribution; West Coast; California; prevalence |
| Arthur CM, Zerra PE, Shin S, Wang J, Song X, Doering CB, Meeks S, Lollar P, Stowell SR. | 2021 | Non-Human Glycans Can Regulate Anti-FVIII Antibody Formation in Mice. |
Blood. 2021 May 21. | medical products; drugs, hemophilia; Recombinant Factor VIII (FVIII) |
| Asaumi T, Ebisawa M. | 2018 | How to manage food dependent exercise induced anaphylaxis (FDEIA). Purpose of review: In recent years, the number of reports on food-dependent exercise-induced anaphylaxis (FDEIA) has been increasing. This review aims to describe the standard management of FDEIA including provocation tests and identify the issues that remain unclear. Recent findings: Provocation tests with aspirin for FDEIA enable us to confirm the definitive diagnosis and to make differential diagnosis. In some cases, FDEIA symptoms can be induced by aspirin and the causative food without exercise. Exercise may only be an augmenting factor of FDEIA, similar to aspirin or alcohol. Summary: The mechanisms of FDEIA development remain unclear. It has been suggested that in FDEIA, exercise lowers the threshold of a food allergy. Further research is needed to elucidate the mechanism of FDEIA and to establish strategies for effective disease management. |
Current opinion in allergy and clinical immunology. 2018 Jun 1;18(3):243-7. | cofactor |
| Atkins J. | 2020 | Regulating the Impending Transformation of the Meat Industry:" Cultured Meat". |
J. Tech. L. & Pol'y. 2019;24:1. | Cultured meat; cell-based meat; law; legal; FDA; USDA |
| Atkinson C, Hatch, R. | 2018 | Resolution of galactose alpha 1-3 galactose (Alpha-Gal) anaphylaxis after tick and hooved meat avoidance. Introduction: Anaphylatic reactions to Alpha-Gal carbohydrate epitope commonly present in meat of hooved animals and are recognized as an important cause of delayed anaphylaxis. Tick bites appear to be a necessary cofactor in developing sensitization to Alpha-Gal. Case Description: Our patient is a 53-year-old female living in Oklahoma who presented to the clinic in 2011 with a two-year history of pruritis, hives, throat tightness, and facial swelling. Symptoms occurred at night after consuming corn or potato chips which had previously been tolerated. Prior to presentation, she had labs drawn which showed elevated counts to pork and beef. It was discovered that six hours after consuming meat she had these episodes and reported having tick bites from her dogs. Percutaneous tests with allergenic extracts showed minimal activity to fresh beef and lamb. Alpha-gal specific IgE was elevated at 65.8 kU/L and she was advised to avoid all meat products except poultry and fish. At four-month follow-up, she continued to avoid pork and beef without further events and had no new tick bites. She had her dogs and home treated for ticks and moved to a new house. At six years after presentation, she reintroduced small amounts of well cooked meat products without problems. Alpha-Gal specific IgE was 0.47 kU/L and continued to decline despite continued meat consumption. . Discussion: This case implies that, at least in this patient, both tick bites and meat exposure are necessary to maintain sensitization. Reintroducing the meat alone without tick exposure did not result in re-sensitization. |
Annals of Allergy, Asthma & Immunology. 2018 Nov 1;121(5):S117. | Oklahoma; vector; tick; sero-reversion |
| Atwal D, Safar AM, Govindarajan R, Makhoul I. | 2019 | Severe first infusion reaction related to cetuximab in cancer patients in Arkansas. Introduction: Cetuximab, a chimeric monoclonal antibody, is a commonly used anticancer drug that prevents binding of epidermal growth factor to epidermal growth factor receptor. It has been widely used in a variety of cancers since its initial approval by the FDA in 2004. Despite its efficacy, it has met with some genuine concerns especially regarding the anaphylactoid reactions occurring after first infusions. Cetuximab-related first infusion reaction has been found to be much more prevalent in the Southeastern United States with several studies from the southern United States supporting it. The purpose of our study was to determine the rate of first infusion reaction in the state of Arkansas and the factors that could predispose to first infusion reaction.Methods and results: We performed a retrospective chart review of consecutive patients who received cetuximab between January 2004 and December 2016 at the University of Arkansas for Medical Sciences. We included a total of 220 patients in our analysis out of which 32 (14.5%) developed cetuximab-related first infusion reaction. There was a statistically significant increased risk in males versus females (18.2% vs. 8.4%, P = 0.045) and trend toward significance for the difference between Caucasians and Blacks (16.5% vs. 7.1%, P = 0.054).Conclusion: There is increased incidence of cetuximab-related first infusion reaction in Arkansas which is much higher than the national average but comparable to the incidence in other neighboring states in the Southeastern United States. This increased incidence tends to cluster in Caucasian males. Safer alternatives should be preferred for treatment of cancers particularly in the Southeastern United States whenever possible. |
Journal of Oncology Pharmacy Practice. 2019 Jul;25(5):1130-4. | pharmacy; pharmaceutical; medication; biologic; biological agent; monoclonal antibody; mAb; cetuximab; demographics; race |
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