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Alpha-Gal or α-Gal

Table of Contents

As we get started, 2 things to remember:

  1. AntigensAntigens are Invaders. or anything our body thinks is an invader lme1
  2. AntibodiesAntibodies are defenders.AS-1

Alpha-Gal and The Alpha-Gal Syndrome (AGS)

You should browse significant Alpha-Gal information source

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

Getting into the weeds

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, which refers to the carbohydrate α-d-Galp-(1 → 3)-β-d-Galp-(1 → 4)-d-GlcNAc-R NIH-4, NIH-5

Symptomstop

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 response that can happen., NIH-74

Unexpeted Sources

  1. CarrageenanAlergy Insider-1
  2. Cat DanderNIH-8, NIH-9

Testing

Reading The Results

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
  1. Concentrations of 0.70 Ku/L or more (Class 2 and above) will flag as abnormally high
  2. Reference values apply to all ages.
  3. The ImmunoCAP test demonstrates patient sensitivity to specific allergens – reporting in number of kilounits per liter (KU/L)
  4. One kU/L is equal to 2.4 ng/mL, NIH-10

Treatments

References:

  1. Top
    Added January 23 2024:
    2020 July: Diagnosis & management of Alpha-Gal syndrome:lessons from 2,500 patients
    • History of a tick bite, larval tick bites (e.g., seed tick bites) or ‘chigger’ bites can be supportive of AGS as a diagnosis but the absence of such a history is not uncommon.
  2. Top
    Added January 23 2024:
    2021 December: The α-Gal Syndrome and Potential Mechanisms

    Besides ticks, it has been suggested that other members of the Arachnida class, Trombiculidae, also commonly known as “chiggers,” may contribute as well to the allergic sensitization to α-Gal.

  3. Top
    Added January 23 2024:
    2018 July: Could chiggers be contributing to the prevalence of galactose-alpha-1, 3-galactose sensitization and mammalian meat allergy?

    This suggests that Alpha-Gal might be present in numerous species of ticks, either intrinsically within tick glycoproteins or as part of microbes within ticks, and raises the possibility of its presence in other mite species known to feed parasitically on mammals, including the Trombiculidae, whose larvae are commonly known as chiggers.

  4. Top
    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.
  5. Top
    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.

  6. Top
    Added February 4 2024:
    2011 December: Fatal Infusion Reactions to Cetuximab: Role of Immunoglobulin E–Mediated Anaphylaxis

    Patients experienced anaphylaxis after receiving Cetuximab treatment.

  7. Top
    Added February 4 2024:
    2019 May: Environmental and Molecular Drivers of the α-Gal Syndrome

    Owing to the continuous antigen stimulation by the gut microbiome, also a large number of blood B lymphocytes have the capability to produce Abs directed against α-Gal. Most of these blood B cells are memory B cells, but once foreign antigens expressing α-Gal enter the body, these anti-α-Gal B cells are stimulated and can produce large amounts of high-affinity α-Gal Abs.

  8. Top
    Added February 4 2024:
    2020 December: α-Gal-Based Vaccines: Advances, Opportunities, and Perspectives

    Immunization by α-Gal, either through injection of synthetic NGPs, or oral administration of α-Gal-expressing bacteria, represents a promising and innovative strategy for the prevention and control of parasitic diseases in humans and animals.

  9. Top
    Added February 5 2024:
    2023 February: AGA Clinical Practice Update on Alpha-Gal Syndrome for the GI Clinician: Commentary
    • Excellent overall view of Alpha-Gal.
    • All doctors must see this!
  10. Top
    Added February 5 2024:
    2021 December: Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism

    Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite.

    This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick.

  11. Top
    Added February 5 2024:
    2013 August: Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits
    • Some reference it as a sugar, a carbohydrate, an Alpha-Gal epitope, some introduce it as a ligand of Anti-Gal (which is is a carbohydrate antigen called the ‘α-Gal epitope’)
  12. Top
    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
  13. Top
    Added June 5 2024:
    2020 Jul.: Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick–Human Skin Interface
    • Ticks secrete various anti-coagulatory, anti-vasoconstrictory, anti-inflammatory, and anti-platelet aggregation factors in their saliva at the bite site during feeding to evade host immunological surveillance and responses.
    • Data showed a novel role of these in vivo exosomes in the inhibition of wound healing
    • Treatment of human skin keratinocytes (HaCaT cells) with exosomes derived from tick saliva/salivary glands or ISE6 cells dramatically delayed cell migration, wound healing, and repair process.
  14. Top
    Added June 6 2024:
    2022 Sep.: The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome
  15. Top
    Added June 10 2024:
    2018 Jan.: Adapting to AGS Part 1: Understanding Tolerance Levels
    • The above link covers:
      • How Tolerance Levels Are Found
      • Tolerance Categories
      • Reducing Environmental Alpha-gal Exposure
      • Keeping Mammalian Pets
      • Airborne Sources of Alpha-gal
      • Cleaning Out The Kitchen
    • Adapting to AGS Part 2: Mammal Ingredient Names
      • The above link covers:
        • It's Complicated (Ingredient lists)
        • Learning Alpha-Gal Ingredients To Avoid
        • Online and Printed Ingredient Data Resources
        • Phone Apps
    • AAdapting to AGS Part 3: Surprising Alpha-Gal Sources
      • The above link covers:
        • Mammal Meat
        • But what about...?
        • Meat Cross-Contamination
        • Dairy and Algae Extracts?
        • Trace Sources
        • Additional Sources
  16. Top
    Added June 12 2024:
    2019 Sep.: Diagnosis and management of patients with the α-Gal syndrome
    • In the USA the lone star tick is the primary cause of this disease but different ticks are responsible in other countries.
    • Blood levels of IgE to α-Gal often drop in patients who avoid recurrent tick bites, but the rate of decline is variable.
  17. Top
    Added June 19 2024:
    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
    • Analyzed the capacity of α‐Gal conjugated proteins and lipids to cross a monolayer of intestinal cells.
    • 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.
  18. Top
    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.
  19. Top
    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.
  20. Top
    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.
  21. Top
    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) had not been recognized until recently.
    • 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.
  22. Top
    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 describe how arrays of oligosaccharide and polysaccharide molecules can be used to investigate these interactions more fully.
  23. Top
    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.
  24. Top
    Added August 18 2024:
    Epub 2023 Aug 7.: Oral immunotherapy in alpha-gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management?
    • Oral immunotherapy (OIT) is a promising treatment for food allergies.
    • The aim was to establish the long-term safety and efficacy of a novel red meat (RM) OIT in galactose-alpha-1,3-galactose (alpha-gal) allergy in adults.
    • Claim: All patients who underwent OIT became tolerant to RM.
    • Our study showed the long-term safety and efficacy of alpha-gal OIT.
    • Alpha-gal sIgE seems to be a potential biomarker to monitor OIT.

Other Follow-up Research :

  1. The α-Galactosyl Carbohydrate Epitope in Pathogenic Protozoa
  2. Mayo Clinic Alpha-Gal Syndrome
  3. Mayo Clinic Testing for: Galactose-Alpha-1,3-Galactose (Alpha-Gal), IgE, Serum
  4. The Alpha-Gal story: Lessons learned from connecting the dots
  5. A pre-defined search argument pointed at the nih.gov website looking for Hs-CRP and fluxuations

Notes