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Alpha-Gal or α-Gal

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.

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

Treatment

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.

  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.
    • Recurrent tick bites induce high levels of anti-α-Gal IgE antibodies that mediate delayed hypersensitivity to consumed red meat products
  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.
  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

Notes