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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
2. AntibodiesAntibodies are defenders.

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

• 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 which is one of 5 types of immunoglobulins (antibodies) produced by our plasma cells.^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.

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}

Symptoms^top

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}

Sources

1. Carrageenan^{Alergy Insider-1}
2. Cat Dander^{NIH-8, NIH-9}

Testing

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

Reference Values

Treatment

Doxycycline?

Discussion

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 scapularis^CDC-2.

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’)

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:

• Can connections be made to bites of blood sucking flies and Alpha-Gal?^{, FIA-1}