Research Regarding Alpha Gal (α Gal)
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As we get started, 2 things to remember:
AntigensAntigens are Invaders. or anything our body thinks is an invader UM1 AntibodiesAntibodies are defenders. AS-1
Alpha-Gal and The Alpha-Gal Syndrome (AGS) Top Return You should browse significant Alpha-Gal information source
Is an allergic reaction associated with bites from; ticks, chiggers, flies and other blood sucking insects.1, 2, 3, 10
Is characterized by a hypersensitivity to the oligosaccharideOligosaccharides are carbohydrates that contain two or more than two monosaccharides (2-10 units of monosaccharides). Based on the number of sugar units they contain, they are of different types. Trisaccharides, tetrasaccharides, pentasaccharides, etc. galactose-alpha-1,3-galactose (also labeled as galactose-α-1,3-galactose) (Alpha-Gal or α-Gal) antigen.In this case the antigen is a carbohydrate molecule epitope. which is another name for a sugar molecule. 4
Can be amplified (made worse) by an increased count of Alpha-Gal epitopes.An epitope is the part of the antigen that binds to a specific antigen receptor on the surface of a B cell. 7
Can be controlled (modulated) by immunoglobulin E (IgE).CDC-1 NIH-1
Has been fatal for some of those receiving Cetuximab for cancer treatment.6
May be an opportunity for crazy science experiments on humans.8
Has a foe - the Anti-Gal.11
The AGS carbohydrate molecule is also considered a sugar found in the tissues of all mammals except humans and other primates. It is also known as mammalian meat allergy, Alpha-Gal allergy, red meat allergy, and tick bite meat allergy.Yale-1
When people who are allergic to Alpha-Gal eat beef, pork, lamb, or meat from other mammals, they have an allergic reaction that causes a range of symptoms, including a rash, nausea, vomiting, and diarrhea. Symptoms usually occur three to six hours after eating. In some cases, people may have an immediate life-threatening anaphylactic reaction that requires medical attention.Yale-1
Humans lack the enzyme necessary to process and break down the Alpha-Gal molecule found in mammals. Therefore, any Alpha-Gal we ingest through red meat or potentially from tick bites remains largely unprocessed in our bodies and winds up acting like a foreign substance (an antigen).NIH-3
It is important to note that a portion of the ingested Alpha-Gal is likely excreted through waste, even without complete processing. Additionally, some gut bacteria may play a role in partially degrading the molecule.
The overall fate of Alpha-Gal in the human body is still an area of active research, with scientists investigating the specific mechanisms involved in its interaction with the immune system and elimination from the body.
Quick Summaries Top Return
1 2 3 4 5 6 7 8 9 An overall view of Alpha-Gal10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Getting into the weeds Top Return If you care to dig deeper into how the antigens and the antibodies interact, start with the α-Gal epitopeAn epitope is the part of the antigen that binds to a specific receptor on the surface of a B cell." B-1 NIH-4 , NIH-5
Symptoms Top Return Blood levels of Alpha-Gal IgE often decrease in patients who avoid recurrent tick bites but the rate of decline varies from patient to patient , NIH-6
One of the symptoms that needs research is the "latent infection"JAMA-1 , NIH-7 4
Unexpeted Sources Top Return
CarrageenanAlergy Insider-1 Cat DanderNIH-8 , NIH-9
Testing Top Return
Test ID: Test ID ALGAL
As an aid in diagnosis of an IgE mediated hypersensitivity allergy to non-primate mammalian red meat, such as beef, pork, venison, and meat-derived products (eg, gelatin)
Reading The Results Top Return Reference Values
Class
IgE kU/L
Interpretation
0
<0.10
Negative
0/1
0.10-0.34
Borderline/equivocal
1
0.35-0.69
Equivocal
2
0.70-3.49
Positive
3
3.50-17.4
Positive
4
17.5-49.9
Strongly positive
5
50.0-99.9
Strongly positive
6
≥100
Strongly positive
Treatments Top Return
Accupuncture? (auricular)
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Doxycycline?
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OIT (Oral immunotherapy)
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Xolair?
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Added August 5 2024:
2020 Feb.: Omalizumab reduces food allergy symptoms in patients with alpha-gal syndrome
Qualifying patients with AGS had urticaria activity score summed over 7 days (UAS7) to assess the itch severity and hive count once daily, before, 4 weeks after and 12 weeks after treatment.
Over a 2 year period, fourteen patients with AGS elected to begin omalizumab treatment for chronic urticaria despite an appropriate mammalian avoidance diet.
Conclusion: Omalizumab appears to effectively treat chronic, spontaneous urticaria developing after a new-onset food allergy and may be associated with improved tolerance of accidental exposure to the relevant allergen, alpha-gal.
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References: Top Return
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Added January 23 2024:
2021 June: Mosquito vector proteins homologous to α1-3 galactosyl transferases of tick vectors in the context of protective immunity against malaria and hypersensitivity to vector bites
Hypersensitivity reactions are commonly elicited by mosquito and tick vector bites.
Three enzymes synthesising the terminal α1-3-linked galactose in α-gal, that are homologous to mammalian α and β1-4 GTs but not mammalian α1-3 GTs, were recently identified in the tick vector Ixodes scapularisCDC-2
The conclusions explained
Looking at the science
α1-3 GTs are special molecules (enzymes) that haven't been fully studied yet, but they seem to be present in some mosquito species.Glycoconjugates can be imagined as sugar chains attached to other molecules. Alpha-Gal (the sugar molecule linked to Alpha-Gal sensitivity) might be part of these chains.Sporozoites are tiny parasites transmitted by mosquitoes that cause malaria.
Connecting the dots
One theory is that these mosquito enzymes (α1-3 GTs) might build sugar chains containing Alpha-Gal.
These sugar chains with Alpha-Gal could then be placed on the surface of the malaria parasite (sporozoite) before the (female) mosquito bites a human.
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Added February 1 2024:
2013 December: Drug allergens and food—the cetuximab and galactose-α-1,3-galactose story
Cancer drug Cetuximab exposes IgE response to the oligosaccharide galactose-α-1,3-galactose (α-gal).
Using an assay for cetuximab with the monoclonal Ab bound to an ImmunoCAP, investigations established that the reactions to cetuximab occurred in patients who had preexisting IgE antibodies to the oligosaccharide on the Fab portion of this molecule.11,12 Galactose-α-1,3-galactose (α-gal) is present at amino acids 88 and 299 on the Fab portion of the heavy chain.13 In fact, of the 21 distinct oligosaccharide structures identified in cetuximab, approximately 30% have at least 1 α-1,3–linked galactosyl residue as measured by peak area at time-of-flight mass spectrometry.13 Thus, cetuximab is in many ways uniquely suited to present α-gal as an antigen and to be used in assays to detect Ab binding to α-gal.
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Added February 4 2024:
2019 May: Environmental and Molecular Drivers of the α-Gal Syndrome
The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals
Recurrent tick bites induce high levels of anti-α-Gal IgE Abs that mediate delayed hypersensitivity to consumed red meat products in humans
This was the first evidence that tick glycoproteins play a major role in allergy development with the potential to cause fatal delayed anaphylaxis to α-Gal-containing foods and drugs and immediate anaphylaxis to tick bites
Initially, it was thought that the origin of tick-derived α-Gal was either residual blood meal mammalian glycoproteins containing α-Gal or tick gut bacteria producing this glycan
However, recently tick galactosyltransferases were shown to be involved in α-Gal synthesis with a role in tick and tick-borne pathogen life cycles
The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick α-Gal, which potentially increases the risk of developing AGS after a bite by a pathogen-infected tick
Two mechanisms might explain the production of anti-α-Gal IgE Abs after tick bites
The first mechanism proposes that the α-Gal antigen on tick salivary proteins is presented to antigen-presenting cells and B-lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva
The second mechanism is based on the possibility that tick salivary prostaglandin E2 triggers Immunoglobulin class switching to anti-α-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-α-Gal IgM and/or IgG
Importantly, blood group antigens influence the capacity of the immune system to produce anti-α-Gal Abs which in turn impacts individual susceptibility to AGS
The presence of blood type B reduces the capacity of the immune system to produce anti-α-Gal Abs, presumably due to tolerance to α-Gal, which is very similar in structure to blood group B antigen
Therefore, individuals with blood group B and reduced levels of anti-α-Gal Abs have lower risk to develop AGS
Specific immunity to tick α-Gal is linked to host immunity to tick bites
Basophil activation and release of histamine have been implicated in IgE-mediated acquired protective immunity to tick infestations and chronic itch
Basophil reactivity was also found to be higher in patients with AGS when compared to asymptomatic α-Gal sensitized individuals
In addition, host resistance to tick infestation is associated with resistance to tick-borne pathogen infection
Anti-α-Gal IgM and IgG Abs protect humans against vector-borne pathogens and blood group B individuals seem to be more susceptible to vector-borne diseases
The link between blood groups and anti-α-Gal immunity which in turn affects resistance to vector-borne pathogens and susceptibility to AGS, suggests a trade-off between susceptibility to AGS and protection to some infectious diseases
The understanding of the environmental and molecular drivers of the immune mechanisms involved in AGS is essential to developing tools for the diagnosis, control, and prevention of this growing health problem
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Added June 4 2024:
2019 May: Environmental and Molecular Drivers of the α-Gal Syndrome
The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick α-Gal, which potentially increases the risk of developing AGS after a bite by a pathogen-infected tick.
Blood group antigens influence the capacity of the immune system to produce anti-α-Gal antibodies which in turn impacts individual susceptibility to AGS.
Individuals with blood group B and reduced levels of anti-α-Gal antibodies have lower risk to develop AGS.
Recurrent tick bites induce high levels of anti-α-Gal IgE antibodies that mediate delayed hypersensitivity to consumed red meat products
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Added July 30 2024:
2024 Feb.: Management of Food Allergies and Food-Related Anaphylaxis
An estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US.
IgE-mediated food allergies may cause anaphylaxis and death.
A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults.
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Added July 31 2024:
2019 Dec.: YOUtube WEBINAR: Alpha-Gal Syndrome: From Diagnosis to (Ingredient) Detective
Provides an overview of Alpha Gal Syndrome (AGS) – the tick-borne condition that renders patients allergic to mammalian meats.
Learn about diagnosis and the key areas of support required for AGS patients of all ages, with a focus on dietary needs and how to be an ingredient detective.
Reviews pharmaceutical considerations (OTC, Rx, and vaccines) and social challenges faced by the patient in the workplace and school, with friends/family, and with their health care team.
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Added August 3 2024:
2015 Jan.: Carbohydrates as food allergens
Previous literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions.
With the rising trends in food allergy prevalence, there was an increasing number of reports of anaphylaxis induced by carbohydrate epitopes.
Unique, pure carbohydrate allergen inducing anaphylaxis, galacto-oligosaccharides in commercial milk formula, has been described in several Asian populations including Singapore.
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Added August 4 2024:
2020 Oct.: The History of Carbohydrates in Type I Allergy
The relevance of carbohydrate specific antibodies as mediators of type I allergy (NIH-11)
Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered clinically irrelevant.
Illustrating the historical development of carbohydrate-allergen-research, reaching from only diagnostically relevant crossreactive-carbohydrate-determinants to clinically important antigens mediating type I allergy.
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Added August 13 2024:
2002 Nov.: Glycan arrays for functional glycomics
Interactions between carbohydrates and proteins mediate intracellular traffic, cell adhesion, cell recognition and immune system function.
Two 2002 papersNIH-12 , NIH-13
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Added August 13 2024:
2020 Jan.: IgE to Galactose-α-1, 3-Galactose Wanes Over Time in Patients Who Avoid Tick Bites
Case reports and clinical experience suggest that levels of IgE to α-Gal can decrease over time in some patients, particularly those who avoid additional tick exposures.
The results further reinforce the connection between tick bites and the syndrome and demonstrate that most subjects (89%) will experience a decline in their α-Gal sIgE titers by avoiding tick bites.
In contrast, many subjects (62%) who experience repeat tick bites will have further rises in their levels of α-Gal sIgE.
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Added October 30 2024:
Epub 2024 Jul 1: Neurosurgical Management of Patients with Alpha-Gal Syndrome
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.
Keywords: alpha-gal syndrome, hemostasis, mammalian products, neurosurgery, anesthesia, gelatin allergy
Table 1. Safe and potentially unsafe medications and surgical products for patients with alpha-gal syndrome.
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Added November 1 2024:
Epub 2013 Feb 23. Gelatin-containing sweets can elicit anaphylaxis in a patient with sensitization to galactose-α-1,3-galactose
Gelatin-containing sweets can elicit anaphylaxis in mammalian meat allergic patients
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.
Keywords: alpha-gal syndrome, hemostasis, mammalian products, neurosurgery, anesthesia, gelatin allergy
Table 1. Safe and potentially unsafe medications and surgical products for patients with alpha-gal syndrome.
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Added December 21 2024:
2024 Jan 22; The α-Gal epitope - the cause of a global allergic disease
The galactose-α-1,3-galactose (α-Gal) epitope is the cause of a global allergic disease, the α-Gal syndrome (AGS).
The α-Gal epitope is highly immunogenic to humans, apes and old-world monkeys, all of which produce anti-α-Gal antibodies of the IgM, IgA and IgG subclasses. Strong evidence suggests that in susceptible individuals, class switch to IgE occurs after several tick bites.
In this review, we discuss the strong immunogenic role of the α-Gal epitope and its structural resemblance to the blood type B antigen.
AGS challenges the current paradigm of food allergy due to several features:
It is the first known allergic disease where a carbohydrate solely is the cause of IgE-mediated allergic reactions.
Patients with AGS develop allergic symptoms several hours (typically 2 – 6 h) after consumption of α-Gal-containing foods
The sensitizing agents are several tick species, but not the food itself.
AGS affects mostly middle-aged patients, although children may also develop the disease.
Individuals expressing the B-antigen (blood group B/AB) seem to have a significantly lower risk of developing AGS
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Added February 12, 2025:
2019 Oct; Only α-Gal bound to lipids, but not to proteins, is transported across enterocytes as an IgE-reactive molecule that can induce effector cell activation
Conclusion: Only α-Gal bound to lipids, but not to proteins, is able to cross the intestinal monolayer and trigger an allergic reaction. This suggests that the slower digestion and absorption of lipids might be responsible for the unusual delayed allergic reactions in α-Gal allergic patients and identifies glycolipids as potential allergenic molecules.
The "greenish" notes are my thoughts, not part of the study.
Question: Since lipids are fats, does this mean ingesting mammal products along with fats, or high fat content meats will exacerbate the allergic response?
Question: Does this indicate that saponin content in ingested foods will affect this allergic response?
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Added February 22, 2025:
Vitamin D is recognized to induce changes in bone metabolism, but it is also able to influence immune response, suppressing mast cell activation and IgE synthesis from B cells and increasing the number of dendritic cells and IL-10-generating regulatory T cells.
Vitamin D deficit has been reported to worsen sensitization and allergic manifestations in several different experimental models. However, in clinical situations, contradictory findings have been described concerning the correlation between allergy and vitamin D deficit.
The aim of this review was to analyze the close relationships between mast cells and vitamin D, which contribute, through the activation of different molecular or cellular activation pathways, to the determination of bone pathologies and the onset of allergic diseases.
Vitamin D and Allergies Vitamin D and Mast Cells: Effects on Allergies
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Added February 22, 2025:
Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals
The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights
The exposure can be trivial, as in mere smelling or being in the vicinity of the food
The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening
In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification
The "greenish" notes are my thoughts, not part of the study.
Question: Might this be an explanation for the "fume effect" experienced by some Alpha Gal sensitive folks?
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Added March 08, 2025:
Carrageenan (CGN) is a high molecular weight polysaccharide extracted from red seaweeds, composed of D-galactose residues linked in β-1,4 and α-1,3 galactose-galactose bond, widely used as a food additive in processed foods for its properties as a thickener, gelling agent, emulsifier, and stabilizer.
In recent years, with the spread of the Western diet (WD), its consumption has increased.
Nonetheless, there is a debate on its safety.
CGN is extensively used as an inflammatory and adjuvant agent in vitro and in animal experimental models for the investigation of immune processes or to assess the activity of anti-inflammatory drugs.
CGN can activate the innate immune pathways of inflammation, alter the gut microbiota composition and the thickness of the mucus barrier.
Clinical evidence suggests that CGN is involved in the pathogenesis and clinical management of inflammatory bowel diseases (IBD), indeed food-exclusion diets can be an effective therapy for disease remission.
Moreover, specific IgE to the oligosaccharide α-Gal has been associated with allergic reactions commonly referred to as the “α-Gal syndrome”.
This review aims to discuss the role of carrageenan in inflammatory bowel diseases and allergic reactions following the current evidence.
Furthermore, as no definitive data are available on the safety and the effects of CGN, we suggest gaps to be filled and advise to limit the human exposure to CGN by reducing the consumption of ultra-processed foods.
Other Follow-up Research Top Return
The α-Galactosyl Carbohydrate Epitope in Pathogenic Protozoa
Mayo Clinic Alpha-Gal Syndrome Mayo Clinic Testing for: Galactose-Alpha-1,3-Galactose (Alpha-Gal), IgE, Serum The Alpha-Gal story: Lessons learned from connecting the dots
Notes
Can connections be made to bites of blood sucking flies and Alpha-Gal?, FIA-1