Materiały źródłowe

• #1 The α-Gal Syndrome and Potential Mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

  The -Gal syndrome is a complex allergic disease characterized by the development of specific IgE antibodies against the carbohydrate galactose–1,3-galactose (-Gal), an oligosaccharide present in cells and tissues of non-primate mammals. […] The review takes a closer look at the immune response against -Gal, in healthy and in -Gal allergic individuals. Furthermore, the similarities and differences between immune response against -Gal and against the other important glycan moieties associated with allergies, namely cross-reactive carbohydrate determinants (CCDs), are discussed. Then different mechanisms are discussed that could contribute to the delayed onset of symptoms after consumption of mammalian meat. […] The tick saliva has been shown to contain proteins carrying -Gal, but also bioactive molecules, such as prostaglandin E2, which is capable of stimulating an increased expression of anti-inflammatory cytokines while promoting a decrease in the production of proinflammatory mediators. Together these components might promote Th2-related immunity and trigger a class switch to IgE antibodies directed against the oligosaccharide -Gal.

• #1 Alpha-gal Syndrome: When a Tick-Bite Turns to a Meat Allergy

  https://asm.org/articles/2023/december/alpha-gal-syndrome-when-a-tick-bite-turns-to-a-mea

  In the U.S., alpha-gal syndrome is triggered by the lone star tick. Alpha-gal syndrome (AGS) is an allergic disease triggered by the bite of the lone star tick that can lead to severe hypersensitivity reactions and anaphylaxis in patients following exposure to red meat. […] Patients with red meat allergy produce specific IgE antibodies to carbohydrate galactose–1,3-galactose (alpha-gal), a carbohydrate found in most mammalian cell membranes. IgE (Immunoglobulin E) antibody production is a response of the immune system to certain allergens. […] In the case of AGS, it seems like primary sensitization happens through the tick’s saliva. […] Hypersensitivity to alpha-gal is also well described after treatment of patients with therapeutics containing the carbohydrate, for example the monoclonal antibody Cetuximab, which is used to treat advanced bowel cancer and head and neck cancers.

• #1 Alpha-gal Syndrome (AGS) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/alpha-gal-syndrome-ags

  Alpha-gal syndrome (AGS) is an allergic condition in which people are allergic to alpha-gal, a sugar found in the tissues of all mammals except humans and other primates. […] When a lone star tick bites someone, it can pass alpha-gal to the person in its saliva. This can trigger the individuals immune system to respond by producing antibodies (known as immunoglobulin E, or IgE) against alpha-gal. This is known as sensitization because the immune system is now sensitive to alpha-gal. […] Over time, the level of IgE antibodies against alpha-gal decreases, and, as a result, some people with AGS may again be able to eat beef, pork, and other mammalian meats and other products that contain alpha-gal without having an allergic reaction. […] The lone star tick can transmit alpha-gal to people through its saliva, which can trigger the immune system to produce antibodies against alpha-gal, causing AGS.

• #1 Alpha-gal Syndrome: When a Tick-Bite Turns to a Meat Allergy

  https://asm.org/articles/2023/december/alpha-gal-syndrome-when-a-tick-bite-turns-to-a-mea

  Notably, research indicates that ticks engorged with human blood exhibit a considerably heightened production of alpha-gal within their salivary glands compared to those feeding on other mammalian hosts. […] While the details of this process remain incompletely understood, the timely removal of ticks during their early feeding stages may potentially mitigate the risk of alpha-gal syndrome. Further investigations are imperative to completely understand the mechanisms at play in primary sensitization and the development of AGS.

• #1 The α-Gal Syndrome and Potential Mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

  The saliva of ticks is a complex mixture of substances, several of them also with immunomodulatory properties. […] With the injury caused by the tick mouthparts that disrupt the epidermis and enter the dermis of the host skin, the mechanisms of wound healing begin in the host: coagulation, vasoconstriction, and platelet aggregation are followed by responses of the innate and adaptive immune system. […] For an effective blood feeding, the tick must be able to counteract the defense mechanisms of the host. Indeed, bioactive molecules present in the tick saliva can suppress the host’s hemostatic as well as immune responses that impede efficient feeding and that might damage the tick. […] These effects might be mediated by molecules such as Prostaglandin E2 (PGE2), which is very abundant in tick saliva. […] The presence of -Gal has also been confirmed in Amblyomma americanum ticks fed on human blood, which lacks -Gal. […] All these findings support the view that -Gal moieties present in tick tissues and saliva do not originate from a prior blood meal but are produced by the ticks themselves.

• #1 The α-Gal Syndrome and Potential Mechanisms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35386980/

  The -Gal syndrome is a complex allergic disease characterized by the development of specific IgE antibodies against the carbohydrate galactose–1,3-galactose (-Gal), an oligosaccharide present in cells and tissues of non-primate mammals. Individuals with IgE antibodies to -Gal suffer from a delayed form of anaphylaxis following red meat consumption. […] This review takes a closer look at the immune response against -Gal, in healthy and in -Gal allergic individuals. Furthermore, the similarities and differences between immune response against -Gal and against the other important glycan moieties associated with allergies, namely cross-reactive carbohydrate determinants (CCDs), are discussed. Then different mechanisms are discussed that could contribute to the delayed onset of symptoms after consumption of mammalian meat. Moreover, our current knowledge on the role of tick bites in the sensitization process is summarized. The tick saliva has been shown to contain proteins carrying -Gal, but also bioactive molecules, such as prostaglandin E2, which is capable of stimulating an increased expression of anti-inflammatory cytokines while promoting a decrease in the production of proinflammatory mediators. Together these components might promote Th2-related immunity and trigger a class switch to IgE antibodies directed against the oligosaccharide -Gal.

• #1 The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3413-z

  Considering these facts, evidence supports a role for -Gal-containing tick salivary proteins in the development of the AGS, possibly in conjunction with other tick salivary components. […] At least two possible mechanisms explain the production in humans of anti–Gal IgE antibodies after tick bites. The first mechanism is supported by our current understanding of the host immune modulation by tick saliva, and proposes that -Gal on tick salivary proteins interacts with antigen-presenting cells (APC) and B lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva. […] This mechanism leads to the elevation of the anti–Gal IgE response. […] The second mechanism needs to be demonstrated, and is based on the possibility that tick saliva contains factors that induce class switch recombination (CSR) to anti–Gal IgE producing B cells of pre-existing B cell clones producing anti–Gal IgM and/or IgG antibodies.

• #1 The α-Gal Syndrome and Potential Mechanisms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35386980/

  Allergic sensitization to -Gal occurs after repeated tick bites. Among immunomodulatory molecules, tick saliva contains proteins glycosylated with -Gal and most likely also -Gal containing glycolipids. -Gal on proteins is recognized by memory B cells expressing anti–Gal B cell receptors. In contrast, glycolipids might be recognized by iNKT cells, which can then produce IL-4. B cells process the glycoproteins and present the peptides to naT cells. In the IL-4 rich milieu, T cells then induce the class switch recombination of B cells leading to the production of IgE to -Gal, which then bind to basophils and mast cells. […] Dietary lipids are broken down into small droplets, which are coated by bile salts and phospholipids to form lipid micelles that are absorbed by the enterocytes. -Gal glycolipids are most likely incorporated into these lipid micelles. In the enterocytes, lipids are packaged into lipoprotein particles, called chylomicrons. In this form, lipids are transported into the lymph via the lacteal vein, reaching the blood stream in the subclavian vein 3 to 4 h after a meal. -Gal molecules would be exposed on the surface of the chylomicrons, allowing the cross-linking of IgE antibodies directed against -Gal. This could explain the delay in the allergic reactions of -Gal allergic individuals after eating red meat. In contrast, glycoproteins carrying -Gal are digested into small peptides and -Gal bound to them into monosaccharides. The postprandial peak of these digestion products, that would be incapable of binding or cross-linking anti–Gal antibodies, occurs approximately 1 or 2 h after ingestion.

• #1 The α-Gal Syndrome and Potential Mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

  The delayed onset of symptoms about 36 h after red meat consumption is indeed remarkable, since IgE-mediated hypersensitivity reactions to foods are usually of rapid onset and symptoms appear within minutes but generally within 2 h after eating the offending food. […] The delay in the occurrence of symptoms after meat consumption was proven in food challenge studies, whereas it was shown that patients’ basophils could be activated immediately upon in vitro exposure to -Gal. […] These findings suggested that the delay in the symptoms is neither caused by an intrinsic property of the carbohydrate nor by a delay in basophil responsiveness, but rather by the time taken by -Gal molecules from the ingestion until the appearance in the circulation. […] Owing to the slower digestion and absorption of lipids as compared to proteins, it was suggested that -Gal bound to lipids, and not to proteins, could be behind the late response of -Gal allergic patients.

• #1 Alpha-gal syndrome: Recognizing and managing a tick-bite–related meat allergy | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/92/5/311

  After individuals sensitized to alpha-gal consume mammalian meat or its derivatives, lipid micelles are formed from glycolipids containing alpha-gal. Enzymes in the small intestine, mainly pancreatic lipase, break down triglycerides within the micelles into free fatty acids, monoglycerides, and diglycerides, which are absorbed by intestinal cells. The intestinal epithelium then converts the fatty acids and monoglycerides into triglycerides and bundles them into lipoprotein particles, or chylomicrons, that display alpha-gal molecules. The chylomicrons enter the lymphatic system via lacteals and reach the bloodstream about 4 hours after a meal, where the alpha-gal molecules bind to alpha-gal-specific IgE antibodies on the surface of basophils or mast cells. This triggers an allergic reaction or anaphylaxis as mast cells release a cascade of allergic mediators, which stimulate sensory nerves, inducing visceral pain through the contraction of intestinal smooth muscles, and activate excessive mucous secretion by the mucous glands.

• #1 Alpha-gal Syndrome | AGI – Alpha-gal Information

  https://alphagalinformation.org/what-is-ags/

  AGS differs from typical allergies in significant ways: AGS is associated with tick bites. It is one of only two carbohydrate allergies that cause life-threatening reactions. Lipids, in addition to proteins, are an important source of the allergen. Its presentation is atypical and includes delayed-onset reactions that can occur 2-10 hours or more after exposure, often in the middle of the night. Reactions do not occur after every exposure or follow an obvious pattern. This lack of consistency has been described as “almost a diagnostic hallmark” by experts. Co-factors such as alcohol consumption and exercise can dramatically impact the severity of reactions or whether they occur at all. […] The allergy component of AGS is only one dimension of a complex immune response that may have other health implications. Conditions tentatively linked to the alpha-gal immune response include some autoimmune diseases, arthritis, and atherosclerosis.

• #1 Alpha-gal syndrome: the first report in Poland

  https://www.termedia.pl/Alpha-gal-syndrome-the-first-report-in-Poland,10,45048,1,1.html

  The latest studies have provided evidence for endogenous antigen synthesis in Ixodes ricinus. […] According to recent reports, the hypersensitive response to alpha-gal might be triggered not only by red meat consumption but also by some drugs containing cross-reactive epitopes, such as cetuximab, an IgG monoclonal antibody drug used in the therapy of one of the most frequent malignancies advanced colorectal cancer. […] The above-mentioned cofactors (exercise, alcohol and nonsteroidal anti-inflammatory drugs) are associated with clinical manifestations of the alpha-gal syndrome. […] The main proposed mechanisms of these observations are an increase in blood circulation and in allergen absorption in the gastrointestinal tract induced by co-factors. […] Alpha-gal allergy is diagnosed on the basis of typical signs and symptoms as well as the measurement of serum IgE antibody levels. […] It is also postulated to use new multiplexed methods such as the FABER test for this purpose. […] Although various commercially available meat extracts are used in diagnostic workup, they may provide false-negative results.

• #1 Mysterious Allergy Caused by Tick Bite: Alpha-Gal Syndrome – Turkish Journal of Parasitology

  https://turkiyeparazitolderg.org/articles/mysterious-allergy-caused-by-tick-bite-alpha-gal-syndrome/doi/tpd.galenos.2024.97720

  Several recent studies have shown a strong association between AGS and tick bites. […] The amount of meat consumed and the presence of cofactors (alcohol, activity, use of spices, menstrual cycles) affect the delay before the reaction and the subsequent clinical signs. […] Specific to AGS, recent tick bites sensitise patients to previously tolerated exposures and even lower the reactivity threshold. […] The -1.3-galactosyltransferase gene (1.3 GT or GGTA1), which has distinctive evolutionary features, has played a crucial role in the evolutionary process of mammalian species. […] The unique distribution and functionality of the -1.3 GT gene across various mammalian taxa underscore its evolutionary significance and potential implications for understanding immunological responses to the -Gal epitope in the context of AGS.

• #1

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The alpha-Gal (-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (-Gal). […] The anti–Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to -Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products. […] A new aspect of the -Gal immune response was the circumstance that an IgE isotype of anti–Gal antibodies with a high anaphylactic potential had been found. […] The reason for this delay of onset is not yet understood, but an association with digestion processes, especially fat digestion, is assumed. […] The consumption of mammalian innards, like pork kidney, takes on a special position in -Gal syndrome as symptoms often are more severe and occur more rapidly.

• #1 The α-Gal Syndrome and Potential Mechanisms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35386980/

  Tick saliva contains immunomodulatory molecules together with -Gal carrying proteins or lipids. Basophils are recruited to the tick-feeding sites and accumulate in the skin after a repetitive tick infestation. Basophils can act as non-professional antigen presenting cells, capable of secreting IL-4. Lipids containing -Gal could also be presented to iNKT cells in the context of CD1d, which are known to produce IL-4 abundantly. IL-4 will skew the differentiation of naT cells recognizing tick saliva antigens into type 2 T helper (Th2) cells. Th2 cells will subsequently interact with anti–Gal-specific B cells and induce class-switch recombination leading to the production of IgE antibodies.

• #1

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The abundance of natural human anti–Gal IgM and IgG antibodies has prompted research on their clinical application in cancer therapy. […] The absence of -Gal is a prerequisite to allow percutaneous sensitization in humans. […] While immune recognition of non-self proteins is well understood as is the cascade of events mounting immune responses of different qualities within the innate and adaptive immune system, characterization of immune check points and consequences in response to non-self carbohydrates is less well characterized. […] To disclose the mechanisms involved specifically in the immune reaction to -Gal, Cretin et al. used Ggta1/T cell receptor beta chain (TCR) double KO mice to investigate if T cells are involved in the induction of anti–Gal antibodies. […] However, for a fundamental and more general understanding of the mechanisms and cell types involved in immunity to carbohydrate allergens, further studies are urgently needed.

• #1

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The -1,3-galactosyltransferase (1,3GT) gene named GGTA1 is present in all mammals, but in humans, apes, and Old World Monkeys, it is inactivated by frame-shift mutations that truncate the expressed protein and abolish its catalytic activity. […] It has indeed been shown that enveloped viruses produced in animal cells or human cells engineered to contain active 1,3GT contain multiple -Gal epitopes on their surface, rendering them more sensitive to lysis by human anti–Gal antibodies and complement. […] The -Gal epitope is also present on other pharmaceuticals and products of animal origin such as gelatin, antivenoms, and bioprosthetic heart valves. […] The -Gal syndrome has been evoked in three cases of cattle workers who presented with allergic symptoms after assisting the veterinarian during calving, representing the first report on -Gal as occupational and respiratory allergen.

• #1 Alpha-gal Syndrome | AGI – Alpha-gal Information

  https://alphagalinformation.org/what-is-ags/

  Alpha-gal syndrome is associated with the bite of certain species of ticks. In different parts of the world, different tick species are implicated. In the United States, the Lone Star Tick is thought to be the primary cause of AGS, based on geographical range and tick salivary factors. […] Preliminary data suggests that exposure to Ascaris lumbricoides roundworms may play a role in both sensitization to alpha-gal and development of alpha-gal syndrome. […] Only a small percentage of people who are bitten by ticks associated with AGS actually develop clinical symptoms. Even if you have been bitten by ticks before and did not develop AGS, a future bite could trigger it. Repeated tick bites are associated with a rise in alpha-gal IgE. Multiple tick bites are associated with the onset of AGS. Many patients report that they were bitten by ticks for many years, and then after being bitten by multiple ticks at once, they developed alpha-gal syndrome.

• #1 Alpha-Gal syndrome Trade-off between allergy and protection to infectious diseases – Research Outreach

  https://researchoutreach.org/articles/alpha-gal-syndrome-trade-off-between-allergy-protection-infectious-diseases/

  The relation between blood type B and the incidence of these infectious diseases is the bona fide example of the trade-off intrinsic to the anti- -Gal immunity. […] Therefore, self-tolerance to blood type B affects the immune response to -Gal, which in turn increases the susceptibility to infectious diseases caused by pathogens carrying -Gal on their surface and, at the same time, decreases the risk to develop AGS after a tick bite. […] The development of a probiotic-based pan-vaccine that can be used to control major infectious diseases caused by pathogen with -Gal on their surface.

• #1 Health: Infectious Disease Epidemiology & Prevention Division: Alpha-gal Syndrome

  https://www.in.gov/health/idepd/zoonotic-and-vectorborne-epidemiology-entomology/vector-borne-diseases/alpha-gal-syndrome/

  Alpha-gal syndrome (AGS) is a serious, potentially life-threatening allergic condition that can occur after a tick bite. […] AGS is not caused by an infection. AGS symptoms occur after people eat red meat or are exposed to other products containing alpha-gal. […] AGS is associated with tick bites. Evidence suggests that AGS is primarily associated with the bite of a lone star tick in the United States, but other kinds of ticks have not been ruled out. […] More research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. […] A diagnosis of alpha-gal syndrome is multi-faceted. […] Most healthcare providers recommend patients diagnosed with AGS stop eating meat from mammals. […] Preventing tick bites is important and may reduce your chances of developing AGS or other tick-borne illnesses.

• #1 Alpha-gal syndrome: the first report in Poland

  https://www.termedia.pl/Alpha-gal-syndrome-the-first-report-in-Poland,10,45048,1,1.html

  Alpha-gal syndrome is an immunoglobulin E (IgE)-dependent allergy to galactose–1,3-galactose (alpha-gal), resulting in a delayed anaphylactic reaction to the consumption of red meat. […] According to recent studies, alpha-gal plays a major role in developing an anaphylactic reaction to red meat. […] Symptoms of alpha-gal syndrome correspond to immediate IgE-mediated hypersensitivity (hives, nausea, rash, dyspnea, dizziness, abdominal pain, diarrhea, loss of consciousness and anaphylactic shock), but occur a few hours after the ingestion of the culprit food, namely, red meat. […] Extended interviews with patients with a history of alpha-gal hypersensitivity revealed that previous exposure to a tick bite might have been the causative factor. […] While Amblyomma americanum is the major tick species that causes morbidity in humans in the United States, Ixodes ricinus is the dominant species in Europe.

• #1 Diagnosis and treatment of the alpha-Gal syndrome | JAA

  https://www.dovepress.com/current-and-future-strategies-for-the-diagnosis-and-treatment-of-the-a-peer-reviewed-fulltext-article-JAA

  The -Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose–1,3-galactose (-Gal) such as mammalian meat or dairy products. […] The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. […] The mechanisms behind tick -Gal induction of sensitization are still unknown, but besides the -Gal moiety, tick sialome components may play an important role in the chained immune reaction activation. […] However, not all individuals bitten by ticks or those that carry elevated specific IgE (sIgE) against -Gal develop AGS, in fact, the majority only produce sIgE against it. […] Anaphylaxis has been triggered in up to 60% of AGS cases and can be fatal if it is not treated promptly.

• #1 CDC: Cases of alpha-gal syndrome from tick bites are rising

  https://www.statnews.com/2023/07/27/alpha-gal-syndrome-lone-star-tick-bite-red-meat-allergy/

  Symptoms include hives, nausea and vomiting, upset stomach and diarrhea, and in extreme cases, anaphylaxis. […] Unlike other food allergies, adverse reactions from alpha-gal are delayed, typically occurring two to six hours after exposure. Onyinye Iweala, an assistant professor in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina at Chapel Hill who studies AGS with Commins, said that this delay may be due to the amount of time it takes for us to absorb molecules that have the alpha-gal sugar on them, process them, package them, and then distribute them to the parts of the body where the allergic immune cells are located. Because of the delay, it takes a really long time to even associate the ingestion of the mammal meat with the development of the allergic symptoms, Iweala said.

• #1 The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3413-z

  This primer focuses on a recently diagnosed tick-borne allergic disease known as the alpha-Gal syndrome (AGS). Tick bites induce in humans high levels of IgE antibodies against the carbohydrate Gal1-3Gal1-(3)4GlcNAc-R (-Gal) present on tick salivary glycoproteins and tissues of non-catarrhine mammals, leading to the AGS in some individuals. This immune response evolved as a conflict and cooperation between ticks and human hosts including their gut microbiota. […] Despite the growing diagnosis of AGS in all world continents, many questions remain to be elucidated on the tick proteins and immune mechanisms triggering this syndrome, and the protective response against pathogen infection elicited by anti–Gal antibodies. […] The AGS is becoming a global problem with increasing prevalence in all continents, and several tick species have been implicated in these disorders.

• #1 The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3413-z

  Tick salivary proteins with or without -Gal modifications that may be involved in triggering the AGS have not been identified, but some -Gal-containing proteins have been shown to be recognized by patients with anaphylactic reaction to tick bite and not by healthy individuals with a record of tick bites. […] The characterization of tick proteins involved in AGS and the immune mechanisms triggering this syndrome is essential to answer the question of why only some individuals develop the AGS in response to tick bites. […] Tick sialome and alphagalactome profiles probably change as tick feeding proceeds thus highlighting the importance of the characterization of proteome changes during tick stages on the host to provide information on the abundance and risks associated with these proteins at different tick feeding stages.

• #1 Diagnosis and treatment of the alpha-Gal syndrome | JAA

  https://www.dovepress.com/current-and-future-strategies-for-the-diagnosis-and-treatment-of-the-a-peer-reviewed-fulltext-article-JAA

  Further diagnostic, treatment and preventive advances will only be possible if the molecular and immune mechanisms behind AGS are uncovered. […] It is of utmost importance to identify tick salivary molecules, with or without -Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development.

• #2 The α-Gal Syndrome and Potential Mechanisms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35386980/

  The -Gal syndrome is a complex allergic disease characterized by the development of specific IgE antibodies against the carbohydrate galactose–1,3-galactose (-Gal), an oligosaccharide present in cells and tissues of non-primate mammals. Individuals with IgE antibodies to -Gal suffer from a delayed form of anaphylaxis following red meat consumption. […] This review takes a closer look at the immune response against -Gal, in healthy and in -Gal allergic individuals. Furthermore, the similarities and differences between immune response against -Gal and against the other important glycan moieties associated with allergies, namely cross-reactive carbohydrate determinants (CCDs), are discussed. Then different mechanisms are discussed that could contribute to the delayed onset of symptoms after consumption of mammalian meat. Moreover, our current knowledge on the role of tick bites in the sensitization process is summarized. The tick saliva has been shown to contain proteins carrying -Gal, but also bioactive molecules, such as prostaglandin E2, which is capable of stimulating an increased expression of anti-inflammatory cytokines while promoting a decrease in the production of proinflammatory mediators. Together these components might promote Th2-related immunity and trigger a class switch to IgE antibodies directed against the oligosaccharide -Gal.

• #2 Alpha-gal syndrome: the first report in Poland

  https://www.termedia.pl/Alpha-gal-syndrome-the-first-report-in-Poland,10,45048,1,1.html

  Alpha-gal syndrome is an immunoglobulin E (IgE)-dependent allergy to galactose–1,3-galactose (alpha-gal), resulting in a delayed anaphylactic reaction to the consumption of red meat. […] According to recent studies, alpha-gal plays a major role in developing an anaphylactic reaction to red meat. […] Symptoms of alpha-gal syndrome correspond to immediate IgE-mediated hypersensitivity (hives, nausea, rash, dyspnea, dizziness, abdominal pain, diarrhea, loss of consciousness and anaphylactic shock), but occur a few hours after the ingestion of the culprit food, namely, red meat. […] Extended interviews with patients with a history of alpha-gal hypersensitivity revealed that previous exposure to a tick bite might have been the causative factor. […] While Amblyomma americanum is the major tick species that causes morbidity in humans in the United States, Ixodes ricinus is the dominant species in Europe.

• #2 Alpha-gal syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Alpha-gal_syndrome

  Alpha-gal allergy is a reaction to the carbohydrate galactose-alpha-1,3-galactose („alpha-gal”), whereby the body is overloaded with immunoglobulin E (IgE) antibodies on exposure to the carbohydrate. […] The tick injects the alpha-gal into a person’s skin with its bite. Recent research has shown that saliva from the lone star tick contains alpha-gal, and that saliva is injected into the bloodstream. […] The immune system then releases a flood of IgE antibodies to fight this foreign sugar. After this reaction, the future intake of mammalian meat with the same alpha-gal causes an allergic reaction. […] Symptoms of the allergy reaction are caused by too many IgE antibodies attacking the allergen the alpha-gal. […] Other types of ticks are suspected of causing similar problems.

• #2 The α-Gal Syndrome and Potential Mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

  The saliva of ticks is a complex mixture of substances, several of them also with immunomodulatory properties. […] With the injury caused by the tick mouthparts that disrupt the epidermis and enter the dermis of the host skin, the mechanisms of wound healing begin in the host: coagulation, vasoconstriction, and platelet aggregation are followed by responses of the innate and adaptive immune system. […] For an effective blood feeding, the tick must be able to counteract the defense mechanisms of the host. Indeed, bioactive molecules present in the tick saliva can suppress the host’s hemostatic as well as immune responses that impede efficient feeding and that might damage the tick. […] These effects might be mediated by molecules such as Prostaglandin E2 (PGE2), which is very abundant in tick saliva. […] The presence of -Gal has also been confirmed in Amblyomma americanum ticks fed on human blood, which lacks -Gal. […] All these findings support the view that -Gal moieties present in tick tissues and saliva do not originate from a prior blood meal but are produced by the ticks themselves.

• #2 The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3413-z

  This finding suggests that while IgG and IgM antibody responses to -Gal produced by some bacteria of the gut microbiota are beneficial as they protect against infection by pathogens such as malaria parasites and tuberculosis mycobacteria, anti–Gal IgE antibodies induced by tick bites break the oral tolerance to food allergens and induce anaphylactic reactions to tick -Gal-containing salivary proteins. […] Tick saliva is a complex mixture of pharmacologically active compounds with a role in tick attachment cement and feeding, pathogen transmission, and the inhibition of host defensive mechanisms through immunomodulatory, anti-hemostatic and anti-inflammatory molecules. […] Recently, we demonstrated that ticks synthesize -Gal with functional GalTs with implications of this protein modification in tick feeding and Anaplasma phagocytophilum infection.

• #2 The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation | Parasites & Vectors | Full Text

  https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3413-z

  Considering these facts, evidence supports a role for -Gal-containing tick salivary proteins in the development of the AGS, possibly in conjunction with other tick salivary components. […] At least two possible mechanisms explain the production in humans of anti–Gal IgE antibodies after tick bites. The first mechanism is supported by our current understanding of the host immune modulation by tick saliva, and proposes that -Gal on tick salivary proteins interacts with antigen-presenting cells (APC) and B lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva. […] This mechanism leads to the elevation of the anti–Gal IgE response. […] The second mechanism needs to be demonstrated, and is based on the possibility that tick saliva contains factors that induce class switch recombination (CSR) to anti–Gal IgE producing B cells of pre-existing B cell clones producing anti–Gal IgM and/or IgG antibodies.

• #2 What Is Alpha-Gal Syndrome? | Allergy Insider

  https://corporate.thermofisher.com/diagnostic-education/patient/us/en/allergy-types/alpha-gal-syndrome.html

  Alpha-Gal syndrome, also known as a delayed mammalian (red) meat allergy (and sometimes mistakenly referred to as alpha-Gal allergy), is a tick-related allergic reaction to a sugar found in red meats, including beef, pork, venison, and lamb. In the United States, alpha-Gal syndrome has been primarily connected to a bite from the Lone Star tick (Amblyomma americanum). This is how it works: First, a bite from a tick can potentially transfer alpha-Gal into a persons bloodstream. In some of the children and adults bitten, that transfer can cause a production of specific IgE which in turn can cause a delayed allergic reaction after they eat red meat. This means an alpha-Gal reaction can appear suddenly in people who have happily eaten meat for years. […] Unlike most food allergies, where symptoms often appear within minutes, symptoms of alpha-Gal syndrome are typically delayed by three to six hours or more. This delay contributes to confusion, as people suffering from the syndrome struggle to connect their reaction to meat consumed hours before.

• #2 The α-Gal Syndrome and Potential Mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

  The delayed onset of symptoms about 36 h after red meat consumption is indeed remarkable, since IgE-mediated hypersensitivity reactions to foods are usually of rapid onset and symptoms appear within minutes but generally within 2 h after eating the offending food. […] The delay in the occurrence of symptoms after meat consumption was proven in food challenge studies, whereas it was shown that patients’ basophils could be activated immediately upon in vitro exposure to -Gal. […] These findings suggested that the delay in the symptoms is neither caused by an intrinsic property of the carbohydrate nor by a delay in basophil responsiveness, but rather by the time taken by -Gal molecules from the ingestion until the appearance in the circulation. […] Owing to the slower digestion and absorption of lipids as compared to proteins, it was suggested that -Gal bound to lipids, and not to proteins, could be behind the late response of -Gal allergic patients.

• #2 Alpha-gal syndrome: Recognizing and managing a tick-bite–related meat allergy | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/92/5/311

  After individuals sensitized to alpha-gal consume mammalian meat or its derivatives, lipid micelles are formed from glycolipids containing alpha-gal. Enzymes in the small intestine, mainly pancreatic lipase, break down triglycerides within the micelles into free fatty acids, monoglycerides, and diglycerides, which are absorbed by intestinal cells. The intestinal epithelium then converts the fatty acids and monoglycerides into triglycerides and bundles them into lipoprotein particles, or chylomicrons, that display alpha-gal molecules. The chylomicrons enter the lymphatic system via lacteals and reach the bloodstream about 4 hours after a meal, where the alpha-gal molecules bind to alpha-gal-specific IgE antibodies on the surface of basophils or mast cells. This triggers an allergic reaction or anaphylaxis as mast cells release a cascade of allergic mediators, which stimulate sensory nerves, inducing visceral pain through the contraction of intestinal smooth muscles, and activate excessive mucous secretion by the mucous glands.

• #2 Alpha-gal Syndrome | AGI – Alpha-gal Information

  https://alphagalinformation.org/what-is-ags/

  AGS differs from typical allergies in significant ways: AGS is associated with tick bites. It is one of only two carbohydrate allergies that cause life-threatening reactions. Lipids, in addition to proteins, are an important source of the allergen. Its presentation is atypical and includes delayed-onset reactions that can occur 2-10 hours or more after exposure, often in the middle of the night. Reactions do not occur after every exposure or follow an obvious pattern. This lack of consistency has been described as “almost a diagnostic hallmark” by experts. Co-factors such as alcohol consumption and exercise can dramatically impact the severity of reactions or whether they occur at all. […] The allergy component of AGS is only one dimension of a complex immune response that may have other health implications. Conditions tentatively linked to the alpha-gal immune response include some autoimmune diseases, arthritis, and atherosclerosis.

• #2 Diagnosis and treatment of the alpha-Gal syndrome | JAA

  https://www.dovepress.com/current-and-future-strategies-for-the-diagnosis-and-treatment-of-the-a-peer-reviewed-fulltext-article-JAA

  Nevertheless, clinical observations in AGS patients are widely variable, showing proof of individual sensitivity. […] Augmenting factors, also called cofactors, such as exercise and alcohol intake, have been reported to play an important role in modulation of this individual susceptibility between patients. […] The sIgE values tend to increase according to the number of tick bites per year and on how recent those bites are. […] The mechanisms behind tick -Gal induction of sensitization are still unknown, but besides the -Gal moiety, tick sialome components may play an important role in the chained immune reaction activation. […] The current diagnostic methods lack specificity or are too risky for routinary appliance, creating the need to overcome these limitations with more precise methods.

• #2

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The abundance of natural human anti–Gal IgM and IgG antibodies has prompted research on their clinical application in cancer therapy. […] The absence of -Gal is a prerequisite to allow percutaneous sensitization in humans. […] While immune recognition of non-self proteins is well understood as is the cascade of events mounting immune responses of different qualities within the innate and adaptive immune system, characterization of immune check points and consequences in response to non-self carbohydrates is less well characterized. […] To disclose the mechanisms involved specifically in the immune reaction to -Gal, Cretin et al. used Ggta1/T cell receptor beta chain (TCR) double KO mice to investigate if T cells are involved in the induction of anti–Gal antibodies. […] However, for a fundamental and more general understanding of the mechanisms and cell types involved in immunity to carbohydrate allergens, further studies are urgently needed.

• #2

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The -1,3-galactosyltransferase (1,3GT) gene named GGTA1 is present in all mammals, but in humans, apes, and Old World Monkeys, it is inactivated by frame-shift mutations that truncate the expressed protein and abolish its catalytic activity. […] It has indeed been shown that enveloped viruses produced in animal cells or human cells engineered to contain active 1,3GT contain multiple -Gal epitopes on their surface, rendering them more sensitive to lysis by human anti–Gal antibodies and complement. […] The -Gal epitope is also present on other pharmaceuticals and products of animal origin such as gelatin, antivenoms, and bioprosthetic heart valves. […] The -Gal syndrome has been evoked in three cases of cattle workers who presented with allergic symptoms after assisting the veterinarian during calving, representing the first report on -Gal as occupational and respiratory allergen.

• #2 Alpha-gal Syndrome | AGI – Alpha-gal Information

  https://alphagalinformation.org/what-is-ags/

  Alpha-gal syndrome is associated with the bite of certain species of ticks. In different parts of the world, different tick species are implicated. In the United States, the Lone Star Tick is thought to be the primary cause of AGS, based on geographical range and tick salivary factors. […] Preliminary data suggests that exposure to Ascaris lumbricoides roundworms may play a role in both sensitization to alpha-gal and development of alpha-gal syndrome. […] Only a small percentage of people who are bitten by ticks associated with AGS actually develop clinical symptoms. Even if you have been bitten by ticks before and did not develop AGS, a future bite could trigger it. Repeated tick bites are associated with a rise in alpha-gal IgE. Multiple tick bites are associated with the onset of AGS. Many patients report that they were bitten by ticks for many years, and then after being bitten by multiple ticks at once, they developed alpha-gal syndrome.

• #2 Alpha-gal Syndrome: When a Tick-Bite Turns to a Meat Allergy

  https://asm.org/articles/2023/december/alpha-gal-syndrome-when-a-tick-bite-turns-to-a-mea

  In the U.S., alpha-gal syndrome is triggered by the lone star tick. Alpha-gal syndrome (AGS) is an allergic disease triggered by the bite of the lone star tick that can lead to severe hypersensitivity reactions and anaphylaxis in patients following exposure to red meat. […] Patients with red meat allergy produce specific IgE antibodies to carbohydrate galactose–1,3-galactose (alpha-gal), a carbohydrate found in most mammalian cell membranes. IgE (Immunoglobulin E) antibody production is a response of the immune system to certain allergens. […] In the case of AGS, it seems like primary sensitization happens through the tick’s saliva. […] Hypersensitivity to alpha-gal is also well described after treatment of patients with therapeutics containing the carbohydrate, for example the monoclonal antibody Cetuximab, which is used to treat advanced bowel cancer and head and neck cancers.

• #2

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The alpha-Gal (-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (-Gal). […] The anti–Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to -Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products. […] A new aspect of the -Gal immune response was the circumstance that an IgE isotype of anti–Gal antibodies with a high anaphylactic potential had been found. […] The reason for this delay of onset is not yet understood, but an association with digestion processes, especially fat digestion, is assumed. […] The consumption of mammalian innards, like pork kidney, takes on a special position in -Gal syndrome as symptoms often are more severe and occur more rapidly.

• #2 Alpha-gal Syndrome: Causes, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/24493-alpha-gal-syndrome

  Alpha-gal syndrome (AGS) occurs due to bites from ticks that carry alpha-gal in their saliva. […] Healthcare providers don’t know the exact reason why alpha-gal triggers sensitivity to red meat or the cancer treatment cetuximab (Erbitux). Researchers also don’t know why some people develop AGS, and others don’t. […] Symptoms occur two to six hours after eating meat or dairy. In some cases, symptoms can occur immediately after exposure to certain products, such as medications containing alpha-gal. […] Treatment for alpha-gal (AGS) syndrome typically involves avoiding foods with alpha-gal and taking medications to manage symptoms that may occur with accidental exposure. Your healthcare provider can work with you to help you avoid products and medications containing alpha-gal.

• #2 What Is Alpha-Gal Syndrome? | Allergy Insider

  https://corporate.thermofisher.com/diagnostic-education/patient/us/en/allergy-types/alpha-gal-syndrome.html

  Because alpha-Gal syndrome symptoms may be delayed by hours, it can be hard to associate the symptoms with eating red meat or a product made with mammalian meat (such as gelatin) hours earlier, not to mention relating it to a tick bite in the past. Since this syndrome was only first reported in the late 2000s, many people are unaware of itincluding healthcare providers. […] Your allergist cannot perform skin-prick tests (SPT) directly for alpha-Gal sensitization, making specific IgE blood testing for the alpha-Gal component the preferred diagnostic method.

• #2 Health: Infectious Disease Epidemiology & Prevention Division: Alpha-gal Syndrome

  https://www.in.gov/health/idepd/zoonotic-and-vectorborne-epidemiology-entomology/vector-borne-diseases/alpha-gal-syndrome/

  Alpha-gal syndrome (AGS) is a serious, potentially life-threatening allergic condition that can occur after a tick bite. […] AGS is not caused by an infection. AGS symptoms occur after people eat red meat or are exposed to other products containing alpha-gal. […] AGS is associated with tick bites. Evidence suggests that AGS is primarily associated with the bite of a lone star tick in the United States, but other kinds of ticks have not been ruled out. […] More research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. […] A diagnosis of alpha-gal syndrome is multi-faceted. […] Most healthcare providers recommend patients diagnosed with AGS stop eating meat from mammals. […] Preventing tick bites is important and may reduce your chances of developing AGS or other tick-borne illnesses.

• #2 Alpha-gal Syndrome (AGS) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/alpha-gal-syndrome-ags

  Alpha-gal syndrome (AGS) is an allergic condition in which people are allergic to alpha-gal, a sugar found in the tissues of all mammals except humans and other primates. […] When a lone star tick bites someone, it can pass alpha-gal to the person in its saliva. This can trigger the individuals immune system to respond by producing antibodies (known as immunoglobulin E, or IgE) against alpha-gal. This is known as sensitization because the immune system is now sensitive to alpha-gal. […] Over time, the level of IgE antibodies against alpha-gal decreases, and, as a result, some people with AGS may again be able to eat beef, pork, and other mammalian meats and other products that contain alpha-gal without having an allergic reaction. […] The lone star tick can transmit alpha-gal to people through its saliva, which can trigger the immune system to produce antibodies against alpha-gal, causing AGS.

• #2 Alpha-gal Information – Alpha-gal Information

  https://alphagalinformation.org/

  Alpha-gal syndrome (AGS), or mammalian meat allergy, is a tick-induced allergy to galactose-α-1,3-galactose. This sugar, commonly known as alpha-gal, is found in all mammals except for humans and some primates. […] In the U.S., lone star tick bites are thought to be the primary source of sensitization. Many other ticks in other parts of the world are also associated with alpha-gal syndrome. […] While it is a growing epidemic, there is still lack of awareness about the alpha-gal syndrome leading to delay in diagnosis and misdiagnosis. […] In geographic areas where tick bites are common, AGS is likely under-recognized and under-diagnosed. We suggest testing for alpha-gal IgE in tick-endemic areas as part of the evaluation for cases of idiopathic anaphylaxis, recurrent urticaria and/or angioedema, as well as recurrent, episodic gastrointestinal cramping of unestablished cause. […] The role and mechanism of galactose-alpha-1,3-galactose in the elicitation of delayed anaphylactic reactions to red meat is significant.

• #3 The α-Gal Syndrome and Potential Mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8974695/

  The delayed onset of symptoms about 36 h after red meat consumption is indeed remarkable, since IgE-mediated hypersensitivity reactions to foods are usually of rapid onset and symptoms appear within minutes but generally within 2 h after eating the offending food. […] The delay in the occurrence of symptoms after meat consumption was proven in food challenge studies, whereas it was shown that patients’ basophils could be activated immediately upon in vitro exposure to -Gal. […] These findings suggested that the delay in the symptoms is neither caused by an intrinsic property of the carbohydrate nor by a delay in basophil responsiveness, but rather by the time taken by -Gal molecules from the ingestion until the appearance in the circulation. […] Owing to the slower digestion and absorption of lipids as compared to proteins, it was suggested that -Gal bound to lipids, and not to proteins, could be behind the late response of -Gal allergic patients.

• #3 The α-Gal Syndrome and Potential Mechanisms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35386980/

  Allergic sensitization to -Gal occurs after repeated tick bites. Among immunomodulatory molecules, tick saliva contains proteins glycosylated with -Gal and most likely also -Gal containing glycolipids. -Gal on proteins is recognized by memory B cells expressing anti–Gal B cell receptors. In contrast, glycolipids might be recognized by iNKT cells, which can then produce IL-4. B cells process the glycoproteins and present the peptides to naT cells. In the IL-4 rich milieu, T cells then induce the class switch recombination of B cells leading to the production of IgE to -Gal, which then bind to basophils and mast cells. […] Dietary lipids are broken down into small droplets, which are coated by bile salts and phospholipids to form lipid micelles that are absorbed by the enterocytes. -Gal glycolipids are most likely incorporated into these lipid micelles. In the enterocytes, lipids are packaged into lipoprotein particles, called chylomicrons. In this form, lipids are transported into the lymph via the lacteal vein, reaching the blood stream in the subclavian vein 3 to 4 h after a meal. -Gal molecules would be exposed on the surface of the chylomicrons, allowing the cross-linking of IgE antibodies directed against -Gal. This could explain the delay in the allergic reactions of -Gal allergic individuals after eating red meat. In contrast, glycoproteins carrying -Gal are digested into small peptides and -Gal bound to them into monosaccharides. The postprandial peak of these digestion products, that would be incapable of binding or cross-linking anti–Gal antibodies, occurs approximately 1 or 2 h after ingestion.

• #3 Diagnosis and treatment of the alpha-Gal syndrome | JAA

  https://www.dovepress.com/current-and-future-strategies-for-the-diagnosis-and-treatment-of-the-a-peer-reviewed-fulltext-article-JAA

  Nevertheless, clinical observations in AGS patients are widely variable, showing proof of individual sensitivity. […] Augmenting factors, also called cofactors, such as exercise and alcohol intake, have been reported to play an important role in modulation of this individual susceptibility between patients. […] The sIgE values tend to increase according to the number of tick bites per year and on how recent those bites are. […] The mechanisms behind tick -Gal induction of sensitization are still unknown, but besides the -Gal moiety, tick sialome components may play an important role in the chained immune reaction activation. […] The current diagnostic methods lack specificity or are too risky for routinary appliance, creating the need to overcome these limitations with more precise methods.

• #3 Could ticks and worms both cause red meat allergy?

  https://www.aaaai.org/tools-for-the-public/latest-research-summaries/the-journal-of-allergy-and-clinical-immunology/2021/ticks

  Alpha-gal allergy or alpha-gal syndrome (AGS) allergy is a type of meat allergy with a delayed onset of symptoms (3-8 hours) after ingesting mammalian meat. […] but the exact mechanism of how a tick bite causes human sensitization against alpha-gal and leads to the development of AGS, is poorly understood. […] The authors demonstrate the presence of alpha-gal containing proteins in two new tick species, and unexpectedly showed an extremely high concentration of an alpha-gal containing protein in the common intestinal parasite Ascaris lumbricoides. […] Moreover, the authors found that the worm extracts and pure worm proteins, are able to induce an allergic reaction in allergy cells that have been primed with serum from patients with alpha-gal allergy, implying that A. lumbricoides infection may cause sensitization to alpha-gal and even lead to meat allergy.

• #3

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  The -1,3-galactosyltransferase (1,3GT) gene named GGTA1 is present in all mammals, but in humans, apes, and Old World Monkeys, it is inactivated by frame-shift mutations that truncate the expressed protein and abolish its catalytic activity. […] It has indeed been shown that enveloped viruses produced in animal cells or human cells engineered to contain active 1,3GT contain multiple -Gal epitopes on their surface, rendering them more sensitive to lysis by human anti–Gal antibodies and complement. […] The -Gal epitope is also present on other pharmaceuticals and products of animal origin such as gelatin, antivenoms, and bioprosthetic heart valves. […] The -Gal syndrome has been evoked in three cases of cattle workers who presented with allergic symptoms after assisting the veterinarian during calving, representing the first report on -Gal as occupational and respiratory allergen.

• #3

  https://link.springer.com/article/10.1007/s11882-019-0835-9

  Angiotensin I-converting enzyme (ACE I) and aminopeptidase N (AP-N), both highly glycosylated proteins of urogenital tissues, were identified as major IgE-binding molecules in pork kidney. […] The presence of -Gal in ticks could be demonstrated by ELISA, immunoblotting techniques, and immunohistochemical staining in various tick species. […] Therefore, it is commonly assumed that tick bites are the most frequent and most important primary sensitization source to -Gal and -Gal syndrome is the first allergy classified as tick-borne disease. […] The geographic outlined accumulation of hypersensitivity in the southeastern US federal states, and the fact that patients developed anaphylaxis on first contact with cetuximab indicated that the patients were presensitized and inducing environmental factors were searched for.

• #3 Alpha-gal Syndrome: Causes, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/24493-alpha-gal-syndrome

  Alpha-gal syndrome (AGS) occurs due to bites from ticks that carry alpha-gal in their saliva. […] Healthcare providers don’t know the exact reason why alpha-gal triggers sensitivity to red meat or the cancer treatment cetuximab (Erbitux). Researchers also don’t know why some people develop AGS, and others don’t. […] Symptoms occur two to six hours after eating meat or dairy. In some cases, symptoms can occur immediately after exposure to certain products, such as medications containing alpha-gal. […] Treatment for alpha-gal (AGS) syndrome typically involves avoiding foods with alpha-gal and taking medications to manage symptoms that may occur with accidental exposure. Your healthcare provider can work with you to help you avoid products and medications containing alpha-gal.

• #3 Genetic and Immunological Insights into Tick-Bite Hypersensitivity and Alpha-Gal Syndrome: A Case Study Approach

  https://www.mdpi.com/1422-0067/26/2/680

  This fact supports the hypothesis that α-Gal-sensitization in humans may be part of acquired tick resistance (ATR) given that humans are not natural hosts for ticks. […] The disease-escaping ability that is achieved through hypersensitivity toward a specific allergen is defined as allergic klenducity, and it is described in several animal species. […] Accordingly, AGS can be observed as a dysbalance of a non-specific immune response against ticks and α-Gal-expressing microorganisms. […] The AGS diagnosis in Patient II is supported by the fact that complete remission was reached (including the resolution of recall urticaria) after the introduction of a restrictive diet, where all mammalian-based food was omitted. […] Our findings provide preliminary evidence that HLA class II loci could serve as AGS susceptibility genetic markers, warranting further investigation into the possible association of AGS with HLA-B27.

• #3 Health: Infectious Disease Epidemiology & Prevention Division: Alpha-gal Syndrome

  https://www.in.gov/health/idepd/zoonotic-and-vectorborne-epidemiology-entomology/vector-borne-diseases/alpha-gal-syndrome/

  Alpha-gal syndrome (AGS) is a serious, potentially life-threatening allergic condition that can occur after a tick bite. […] AGS is not caused by an infection. AGS symptoms occur after people eat red meat or are exposed to other products containing alpha-gal. […] AGS is associated with tick bites. Evidence suggests that AGS is primarily associated with the bite of a lone star tick in the United States, but other kinds of ticks have not been ruled out. […] More research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. […] A diagnosis of alpha-gal syndrome is multi-faceted. […] Most healthcare providers recommend patients diagnosed with AGS stop eating meat from mammals. […] Preventing tick bites is important and may reduce your chances of developing AGS or other tick-borne illnesses.

• #4 Alpha-gal syndrome: Recognizing and managing a tick-bite–related meat allergy | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/92/5/311

  Alpha-gal, the allergen identified in alpha-gal syndrome, is an oligosaccharide found in the cells and tissues of all nonprimate mammals. Sensitization to alpha-gal is thought to occur through parasitic infections, most commonly tick bites, when the immune system produces IgE antibodies directed against alpha-gal present in the parasites saliva. According to Commins et al, 80% of patients with suspected alpha-gal syndrome report being bitten by ticks, and these individuals have higher alpha-gal IgE levels than those who have not been bitten. […] Although the exact pathogenesis of alpha-gal syndrome is unknown, it involves IgE-mediated activation of mast cells after mammalian meat is consumed. The current glycolipid hypothesis describes the mechanism for the delay in response to ingestion of meat products containing alpha-gal and subsequent development of symptoms.

• #4 Mysterious Allergy Caused by Tick Bite: Alpha-Gal Syndrome – Turkish Journal of Parasitology

  https://turkiyeparazitolderg.org/articles/mysterious-allergy-caused-by-tick-bite-alpha-gal-syndrome/doi/tpd.galenos.2024.97720

  Several recent studies have shown a strong association between AGS and tick bites. […] The amount of meat consumed and the presence of cofactors (alcohol, activity, use of spices, menstrual cycles) affect the delay before the reaction and the subsequent clinical signs. […] Specific to AGS, recent tick bites sensitise patients to previously tolerated exposures and even lower the reactivity threshold. […] The -1.3-galactosyltransferase gene (1.3 GT or GGTA1), which has distinctive evolutionary features, has played a crucial role in the evolutionary process of mammalian species. […] The unique distribution and functionality of the -1.3 GT gene across various mammalian taxa underscore its evolutionary significance and potential implications for understanding immunological responses to the -Gal epitope in the context of AGS.

• #4 Alpha-Gal Allergy – with Dr. Scott Commins | Department of Medicine

  https://www.med.unc.edu/medicine/news/chairs-corner/podcast/alpha-gal/

  We essentially called back our patients we had been enrolling in our meat allergy study, and this was largely my role—and began asking them questions related to their tick bite history, exposure, settings where they were, and began to piece the puzzle together. […] Ultimately, we’re working on a mouse model where we can inject tick extract into a certain type of mouse. These mice produce the same allergic response to alpha-gal that our patients do. That so far has been the best indication. […] We think it takes on the order of four to six weeks. […] The test is quite sensitive. […] It is not very specific. […] In some ways, I think it’s a marker for tick bites, and perhaps other bites as well, but only a small fraction of people who test positive truly develop allergic responses after eating mammalian meat.

• #4 Alpha-gal Syndrome (AGS) 2022 Case Definition | CDC

  https://ndc.services.cdc.gov/case-definitions/alpha-gal-syndrome-ags-2022/

  Alpha-gal Syndrome (AGS) is a hypersensitivity reaction to galactose–1,3-galactose (alpha-gal), found in non-primate mammalian meat and certain derivative products. […] Evidence suggests that the bite of some tick species induces immunoglobulin E (IgE) antibodies to alpha-gal, sensitizing patients to subsequent alpha-gal exposures. […] Research has suggested that other tick species, including Ixodes spp., may also be associated with AGS development. […] Preventing tick bites is the main strategy for AGS intervention; disease surveillance could, therefore, inform activities to strengthen occupational health protocols of suspected risk groups and public health messaging regarding tick bite prevention behaviors, with the goal of reducing tick borne disease risk.

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