Research Regarding Alpha Gal (α Gal)

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As we get started, 2 things to remember:

1. AntigensAntigens are Invaders. or anything our body thinks is an invader ^UM1
2. 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 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.

Quick Summaries^{Top Return}

• ¹Diagnosis & management of alpha-Gal syndrome
• ²Chiggers as well as ticks
• ³Multiple species of ticks have been implicated in Alpha-Gal sensitization
• ⁴Some species of mosquitos are possible vectors
• ⁵Cetuximab exposes IgE Alpha-Gal (α-Gal) response
• ⁶Anaphylaxis after receiving Cetuximab
• ⁷Some people with blood type B seem to have a lower prevalence of the allergy compared to other blood types
• ⁸Vaccines and other options
• ^{9An overall view of Alpha-Gal}
• ¹⁰A look into tick metabolism and enzymes
• ¹¹Anti-gal: an abundant human natural antibody
• ¹²Recurrent tick bites induce high levels of anti-α-Gal IgE
• ¹³Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick–Human Skin InterfaceE
• ¹⁴Managing Alpha-Gal Syndrome
• ¹⁵Adapting to Alpha Gal Parts 1, 2, and 3
• ¹⁶Diagnosis and management of patients with the α-Gal syndrome
• ¹⁷α‐Gal bound to lipids, but not to proteins is the culprit
• ¹⁸Management of Food Allergies and Food-Related Anaphylaxis
• ¹⁹ YOUtube WEBINAR: Alpha-Gal Syndrome: From Diagnosis to (Ingredient) Detective
• ²⁰Carbohydrates identified as allergens in 2015
• ²¹The History of Carbohydrates in Type I Allergy
• ²²Glycan arrays for functional glycomics
• ²³Alpha Gal Wanes Over Time in Patients Who Avoid Tick Bites
• ²⁴Oral immunotherapy in alpha-gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management?
• ²⁵Anaphylaxis after receiving zoster vaccine.
• ²⁶Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis.
• ²⁷Gelatin-containing sweets can elicit anaphylaxis in mammalian meat allergic patients.
• ²⁸Over time, the level of IgE antibodies against alpha-gal decreases.
• ²⁹It is the first known allergic disease where a carbohydrate solely is the cause of IgE-mediated allergic reactions.
• ³⁰AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity.
• ³¹mRNA possible catalyst for AGS.

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, which refers to the carbohydrate α-d-Galp-(1 → 3)-β-d-Galp-(1 → 4)-d-GlcNAc-R ^{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 response that can happen.^{, NIH-74}

Unexpeted Sources^{Top Return}

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

Treatments^{Top Return}

• Accupuncture? (auricular)
1. Top Return
Added June 12 2024:
2021 Oct.: Successful Treatment for Alpha Gal Mammal Product Allergy Using Auricular Acupuncture: A Case Series
• Of 137 people treated with accupuncture in the ear, 121 (96%) patients indicated that their symptoms were in remission after treatment. Five individuals indicated that their symptoms were not in remission. Eleven individuals were unsure of treatment response or unable to be reached for follow-up.
• No adverse reactions were noted as a result of auricular acupuncture.
2. Top Return
Added June 12 2024:
2014 Apr.: A Comparison Study of the Effectiveness of SAAT (Soliman's Auricular Allergy Treatment) Approach and Nogier's Allergy Treatment Technique
• Conclusions: The SAAT technique appears to be superior to Nogier's allergy treatment technique for eliminating allergies regardless of their origins.
• Doxycycline?
1. Top Return
Added June 7 2024:
2015 Feb.: Novel Description of PolyarthralgiaPolyarthralgia is pain in multiple joints, usually two or more. It can be a symptom of a number of conditions, including: Inflammatory joint pain: Such as rheumatoid arthritis or juvenile polyarthritis Mechanical joint pain: Such as osteoarthritis Non-articular disease: Such as fibromyalgia or polymyalgia rheumatica Other symptoms of polyarthralgia include: tenderness, tingling, and reduced range of motion. with Alpha-Gal Allergy
• Empirically treated with doxycycline 100mg by mouth twice daily for 10 days and had complete resolution of polyarthralgia and fatigue.
• Treating the symptoms not the cause
2. Top Return
Added June 7 2024:
2022 Dec.: Alpha-Gal Syndrome in the Infectious Diseases Clinic: A Series of 5 Cases in Central North Carolina
• Some experienced relief, some did not. Inclusion of diet changes were not always mentioned or mentioned as an after-thought.
• Treating the symptoms not the cause.
• OIT (Oral immunotherapy)
1. Top Return
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.
• Xolair?
1. Top Return
Added August 5 2024:
2020 Mar.: Omalizumab may help treat red meat allergy caused by tick bites
• American Academy of Allergy, Asthma & Immunology Annual Meeting
• A small study that was to be presented at the American Academy of Asthma, Allergy & Immunology Annual Meeting. The meeting was canceled because of concerns about COVID-19, the disease caused by the novel coronavirus.
2. Top Return
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.
3. Top Return
Added August 5 2024:
2016 Feb.: PDF from FDA: HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use XOLAIR safely and effectively. See full prescribing information for XOLAIR.
• DOES NOT MENTION "ALPHA GAL"
• Was originally approved by FDA (2003) for use in asthma treatment.
• January 2024 was approved by FDA as food allergy treatment.
• Last change to this PDF was 07/2016.
• Make sure you Dr. is aware of the following statement in this document: A case-control study showed that, among Xolair users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with Xolair, compared to those with no prior history of anaphylaxis [see Adverse Reactions (6.1)]
4. Top Return
Added August 5 2024:
2024 Feb.: FDA approves Xolair® (omalizumab) as first and only medicine for children and adults with one or more food allergies
• DOES NOT SPECIFICALLY MENTION "ALPHA GAL"
• Novartis announced that the US Food and Drug Administration (FDA) has approved Xolair® (omalizumab) for the reduction of allergic reactions, including anaphylaxis.
• Mentioned were; patients aged 1 to 55 years allergic to peanuts and at least two other food allergens, including milk, egg, wheat, cashew, hazelnut and walnut.
References:^{Top Return}
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Added January 23 2024:
2020 July: Diagnosis & management of Alpha-Gal syndrome:lessons from 2,500 patients
• 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
• IgE varies with the change in meat consumption, according to quantity, quality and type.
^{Top Return}
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
^{Top Return}
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.
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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 scapularis^CDC-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.
^{Top Return}

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.

^{Top Return}

Added February 4 2024:

2011 December: Fatal Infusion Reactions to Cetuximab: Role of Immunoglobulin E–Mediated Anaphylaxis

Patients experienced anaphylaxis after receiving Cetuximab treatment.

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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
^{Top Return}

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.

^{Top Return}
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!
^{Top Return}

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.

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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’)
^{Top Return}
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
^{Top Return}
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.
^{Top Return}
Added June 6 2024:
2022 Sep.: The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome
• List of ticks associated with Alpha-Gal
^{Top Return}
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
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
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 papers^{NIH-12, NIH-13} describe how arrays of oligosaccharide and polysaccharide molecules can be used to investigate these interactions more fully.
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
Added October 29 2024:
Epub 2016 Dec. 14.: Anaphylaxis after Zoster Vaccine: Implicating Alpha-Gal Allergy as a Possible Mechanism
• A patient with alpha-gal allergy presented with anaphylaxis after receiving zoster vaccine.
• Subsequent testing of selected vaccines revealed the presence of alpha-gal allergen in MMR and zoster vaccines
• higher content of gelatin and content of bovine calf serum in MMR and zoster vaccines.
• Reported Gelatin or Mammal Derived Product Content of Selected Vaccines
^{Top Return}
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.
^{Top Return}
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.
^{Top Return}
Added November 2 2024:
Yale Medicine Alpha Gal (AGS) webpage
• Over time, the level of IgE antibodies against alpha-gal decreases.
^{Top Return}
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:
1. It is the first known allergic disease where a carbohydrate solely is the cause of IgE-mediated allergic reactions.
2. Patients with AGS develop allergic symptoms several hours (typically 2 – 6 h) after consumption of α-Gal-containing foods
3. The sensitizing agents are several tick species, but not the food itself.
4. AGS affects mostly middle-aged patients, although children may also develop the disease.
5. Individuals expressing the B-antigen (blood group B/AB) seem to have a significantly lower risk of developing AGS
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Added January 26 2025:
2024 June; Tick bites, IgE to galactose-alpha-1,3-galactose and urticarial or anaphylactic reactions to mammalian meat: The alpha-gal syndrome
• In addition to classic allergic symptomatology such as urticaria and anaphylaxis, AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity and alpha-gal sensitization has also been linked with cardiovascular disease.
^{Top Return}
Added January 26 2025:
2025 Jan; Alpha-Gal Syndrome A Growing Health Care Concern
• In humans, old-world monkeys, and apes the GGTA1 gene, which encodes the enzyme alpha-1,3-galactosyltransferase, seemingly became defective during mammalian development due to a frameshift mutation.A frameshift mutation is a genetic mutation caused by a deletion or insertion in a DNA sequence that shifts the way the sequence is read. ^{Nature-1, X-comments, RGate-1}
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Added February 12, 2025:

Is Glycerin Vegan? What To Know

Section "Is Glycerin Vegan" speaks to glycerol possibly being animal based.

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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:
2022 Aug 3; Mast Cells and Vitamin D Status: A Clinical and Biological Link in the Onset of Allergy and Bone Diseases
• 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:
2009 Feb 20; Food hypersensitivity by inhalation
• 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?
Other Follow-up Research^{Top Return}
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}