Murangi T, Mans B, Pienaar R, Botha M, Facey-Thomas H, et al.
The journal of allergy and clinical immunology. Global •
The presence of galactose-α-1,3-galactose (alpha-gal) in tick salivary antigens has been implicated to initiate host IgE responses resulting in sensitization to alpha-gal. We sought to investigate the presence of alpha-gal in different anatomic locations in native South African tick species at different feeding and developmental stages and the ability of sera from our allergic cohort to bind to these tick proteins. Alpha-gal-containing proteins in laboratory-reared ticks at different feeding and developmental stages were detected through Western blotting and immunohistochemical staining. IgE and IgG4 toward the tick proteins were analyzed via ELISA. There is differential expression of alpha-gal in endemic South African ticks and . Immunoblotting demonstrated an increase in the prominence of alpha-gal-containing protein bands in salivary glands to be proportional to feeding time. Alpha-gal in both fed and unfed ticks was localized in the salivary acini and testes. IgE and IgG4 to antigens were significantly raised in alpha-gal-allergic individuals. There was a correlation between anti- IgE and anti-alpha-gal IgE in the alpha-gal-allergic group. Inhibition of human serum anti-alpha-gal IgE to and proteins was significantly reduced by the addition of bovine thyroglobulin. We anticipate repeated exposure to differentially expressed and alpha-gal-containing salivary proteins during feeding to cause alpha-gal sensitization.
Alpha-gal syndrome (AGS) is caused by IgE antibodies against the alpha-gal oligosaccharide, which is structurally similar to the Group B antigen. Recent case reports of severe allergic transfusion reactions (ATRs) in Group O patients receiving Group B plasma and platelets raise the possibility of a new adverse event, herein called transfusion-related AGS (TRAGS). The primary goal of this study was to assess the frequency of Groups B and AB plasma and platelet transfusions to Group O patients. In this multi-site retrospective study, participating sites submitted the numbers of platelet and plasma transfusions administered during a 2-year period categorized by patient and product ABO group. Fourteen sites from 10 countries participated. Group O patients received Group AB for an average of 9.9% (range 2.8%-29.2%) of plasma transfusions and Group B for 3.2% (0%-12.8%). AB plasma transfusion to Group O patients represented 4.5% (0.9%-14.6%) of the total plasma transfused; Group B 1.4% (0%-5.1%). Group O patients received Group AB for an average of 1.5% (range 0%-5.9%) of platelet transfusions and Group B for 4.1% (0%-14.2%). AB platelet transfusion to Group O patients represented 0.6% (0%-2.7%) of the total platelets transfused; Group B platelets were 1.8% (0%-6.7%). Evidence supporting the possibility of a new adverse event, TRAGS, is accumulating. This study quantifies how often Group O patients may be exposed to Group B antigen in Group B or AB plasma and/or platelet transfusions, providing an estimate of the scope of potential risk for TRAGS.
Wilson JM, Erickson L, Levin M, Ailsworth SM, Commins SP, et al.
Allergy •
The recent recognition of a syndrome of tick-acquired mammalian meat allergy has transformed the previously held view that mammalian meat is an uncommon allergen. The syndrome, mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Thus, fittingly, this allergic disorder is now called the alpha-gal syndrome (AGS). The syndrome is strikingly regional, reflecting the important role of tick bites in sensitization, and is more common in demographic groups at risk of tick exposure. Reactions in AGS are delayed, often by 2-6 h after ingestion of mammalian meat. 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. The unusual link with tick bites may be explained by the fact that allergic cells and mediators are mobilized to the site of tick bites and play a role in resistance against ticks and tick-borne infections. IgE directed to alpha-gal is likely an incidental consequence of what is otherwise an adaptive immune strategy for host defense against endo- and ectoparasites, including ticks.
McGill SK, Levin ME, Shaheen NJ, Cotton CC, Platts-Mills TA, et al.
Journal of clinical gastroenterology •
Alpha-gal allergy causes a delayed reaction to mammalian meats and has been reported worldwide. Patients with the allergy may present with isolated gastrointestinal (GI) symptoms, but this phenotype is poorly understood. We pooled and analyzed symptoms and demographics of patients from two prospective cohorts of patients with a diagnosis of alpha-gal allergy who reacted after eating mammalian meat under observation. We compared the characteristics of patients who demonstrated GI-isolated symptoms on a challenge with those who exhibited symptoms outside the GI tract (skin, respiratory, and circulatory). Among the 91 children and adult alpha-gal allergic patients who exhibited symptoms after oral challenge with mammalian meat, 72.5% experienced GI distress with one or more GI symptoms, which was the most frequent class of symptoms, compared with skin changes in 57.1% and respiratory distress in 5.5%. The most common GI symptoms were abdominal pain (71%) and vomiting (22.0%). GI-isolated symptoms occurred in 37 patients (40.7%) who reacted, and those patients reacted more quickly than patients who exhibited systemic symptoms (median onset of symptoms in GI-isolated group 90 min vs 120 min) and were more likely to be children than adults (relative risk=1.94, 95% CI: 1.04-3.63). Isolated-GI distress occurred in 4 in every 10 alpha-gal allergic individuals who developed symptoms on oral food challenge with mammalian meat. Alpha-gal allergic patients, particularly children, may exhibit GI distress alone, and adult and pediatric gastroenterologists should be aware of the diagnosis and management of the allergy.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology •
The prevalence and awareness of food allergy (FA) among US adults is arguably at a historical high, both with respect to primary immunoglobulin E-mediated food hypersensitivity and other food-triggered conditions that operate through a variety of immunologic mechanisms (eg, pollen-FA syndrome, alpha-gal syndrome, food protein-induced enterocolitis syndrome, eosinophilic esophagitis). Worryingly, not only are many adults retaining childhood-onset food allergies as they age into adulthood, it seems that many adults are experiencing adult-onset allergies to previously tolerated foods, with correspondingly adverse physical, and psychological health impacts. Consequently, this review aims to summarize what is currently known about the epidemiology and population-level burden of FA among adult populations in North America and around the globe. This article also provides insights into the natural history of these conditions and what we need to know as we look to the future to support effective care and prevent FA.
Murangi T, Prakash P, Moreira BP, Basera W, Botha M, et al.
The Journal of allergy and clinical immunology •
IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied. Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal-containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model. Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system. Alpha-gal IgE level correlated with A lumbricoides-specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non-alpha-gal-containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome. We demonstrated the presence, relative abundances, and site of localization of alpha-gal-containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non-alpha-gal-containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity.
Mittermann I, Dzoro S, Gattinger P, Botha M, Basera W, et al.
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology •
Allergens can act as disease-triggering factors in atopic dermatitis (AD) patients. The aim of the study was to elucidate the molecular IgE sensitization profile in children with and without AD living in urban and rural areas of South Africa. Specific IgE reactivity was assessed in 166 Black South African children aged 9-38 months using a comprehensive panel of microarrayed allergens. According to clinical characterization children fell in four groups, urban AD cases (n = 32), urban controls (non-AD, n = 40), rural cases (n = 49) and rural controls (non-AD, n = 45). IgE reactivity to at least one of the allergens was detected in 94% of urban and 86% of rural AD children. House dust mite (HDM; 81% urban, 74% rural AD) and animal-derived allergens (50% urban, 31% rural AD) were the most frequently recognized respiratory allergens, whereas IgE to pollen allergens was almost absent. Urban AD children showed significantly higher frequency of IgE reactivity (50%) to mouse lipocalin, Mus m 1, than rural AD children (12%). The most frequently recognized food allergens were from egg (63% urban, 43% rural AD), peanut (31% vs 41%), and soybean (22% vs 27%), whereas milk sensitization was rare. α-gal-specific IgE almost exclusively occurred in rural children (AD: 14%, non-AD: 49%). Molecular allergy diagnosis detects frequent IgE sensitization to HDM, animal but not pollen allergens and to egg, peanut, and soy, but not milk allergens in African AD children. Urban AD children reacted more often to Mus m 1, whereas α-gal sensitization is more common in rural children likely due to parasite exposure.
Platts-Mills TAE, Commins SP, Biedermann T, van Hage M, Levin M, et al.
The Journal of allergy and clinical immunology •
The mammalian meat allergy known as the "α-Gal syndrome" relates to IgE specific for galactose-α-1,3-galactose (α-Gal), an oligosaccharide that is present in cells and tissues of nonprimate mammals. The recognition of delayed reactions to food derived from mammals in patients with IgE to α-Gal and also the association with tick bites have been increasing worldwide. In 2018, the National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology and Transplantation, sponsored a workshop on this emerging tick-related disease. International experts from the fields of tick biology, allergy, immunology, infectious disease, and dermatology discussed the current state of our understanding of this emerging medical condition. The participants provided suggestions for specific research priorities and for the development of resources to advance our knowledge of the mechanisms, diagnosis, management, and prevention of this allergic disease. This publication is a summary of the workshop and the panel's recommendations are presented herein.
Levin M, Apostolovic D, Biedermann T, Commins SP, Iweala OI, et al.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology •
To review published studies on galactose α-1,3-galactose (α-gal), a carbohydrate epitope found on proteins and lipids in nonprimate mammals and present in foods (particularly organ or fat-rich red meat) and medications, where it causes delayed-onset and immediate-onset anaphylaxis. A literature search for the terms galactose α-1,3-galactose and α-gal using PubMed and Embase was performed. Studies on α-gal were included in this review. Several species of ticks contain α-gal epitopes and possibly salivary adjuvants that promote high titer sensitization and clinical reactivity. Risk factors for α-gal syndrome include exposure to ticks of particular species. Age and sex differences seen in various cohorts possibly reflect the prevalence of these exposures that vary according to setting. The reason and mechanisms for delayed onset of food-related anaphylaxis and the preponderance of abdominal reactions are not clear but may involve the kinetics of allergen digestion and processing or immunologic presentation via a different mechanism from usual immediate-type food allergy.
African journal of primary health care & family medicine •
An allergic reaction to mammalian meat has recently been reported in rural parts of South Africa and throughout other parts of the world. The cause of this allergic reaction is because of an oligosaccharide antigen known as galactose-alpha-1, 3-galactose (alpha-gal) found in mammalian meat. Hard ticks in various parts of the world have been identified as a cause of sensitisation to the alpha-gal antigen. However, mechanisms of sensitisation in Africa are poorly understood. The aim of this article is to review current literature on the alpha-gal allergy and mammalian meat ingestion and the family physician's role in diagnosing and managing this condition. Indexes were searched using the keywords in the following electronic databases: Elsevier Science Direct, Google Scholar, Medline and PubMed. Clinical presentation of the alpha-gal allergy occurs typically as a delayed anaphylaxis occurring within 3-6 hours after the ingestion of mammalian meat. A subset of patients described in South Africa presented with a rapid onset of symptoms occurring within 45 minutes. Furthermore, some of these patients present with abdominal symptoms only, which may be mistaken as food poisoning. Diagnosis is based on a history of reaction to mammalian meats (especially to fatty portions or organs) and serum specific alpha-gal antibodies. The main management of the alpha-gal allergy is avoidance of red meat and in mild reactions treatment with oral H1 receptor antihistamines. Sensitisation to the alpha-gal allergy results in adverse reactions to red meat, with tolerance to turkey, chicken and fish. A family physician can safely manage this condition.
Mabelane T, Basera W, Botha M, Thomas HF, Ramjith J, et al.
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology •
Severe meat allergy with anaphylaxis may be caused by sensitization to alpha-gal. Levels of alpha-gal sensitization that correlate with high risk of meat allergy are currently unknown. We have identified an area with a high prevalence of reported red meat allergy which offered the opportunity to evaluate the diagnostic value of IgE antibody tests. To determine levels of alpha-gal IgE and alpha-gal:total IgE ratio in a large cohort of subjects with challenge-proven meat allergy compared with control subjects from the same environment, we conducted fieldwork assessing 131 participants who reported adverse reactions to meat, and 26 control subjects, by questionnaires, IgE sensitization to alpha-gal and oral food challenge to beef sausage. Eighty-four participants were diagnosed with alpha-gal allergy. Alpha-gal IgE ranged between 0.7 and 344.5Â kU/L. Alpha-gal:total IgE ratio ranged from 0.1% to 67.6%. Logistic regression analysis showed both alpha-gal IgE and alpha-gal:total IgE ratio strongly correlated with meat allergy, with AUC of 0.95. The values giving the best correct classification were IgE of 2.00Â kU/L and ratio of 0.75%. The value above which there is a 95% probability of meat allergy is IgE>5.5Â kU/L and ratio of 2.12%. Alpha-gal allergy in a population with a high prevalence of reported red meat allergy showed a more rapid onset of symptoms than previously described and a high prevalence of isolated subjective gastrointestinal manifestations. Cutoff values are described for levels of sensitization to alpha-gal IgE and alpha-gal:total IgE ratio that are highly likely to result in clinically significant meat allergy.
