Levin ME

University of Cape Town

5
Publications
38
h-index
(6,474 citations, 227 total works)

Research Topics

Food Allergy and Anaphylaxis Research (88)Asthma and respiratory diseases (80)Allergic Rhinitis and Sensitization (69)Dermatology and Skin Diseases (27)Eosinophilic Esophagitis (18)

Alpha-gal Syndrome Publications

Differential alpha-gal expression during and tick feeding and development: A driver for the development of alpha-gal syndrome in South Africa.

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.

Tick bites, IgE to galactose-alpha-1,3-galactose and urticarial or anaphylactic reactions to mammalian meat: The alpha-gal syndrome.

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.

Gastrointestinal-isolated Distress is Common in Alpha-gal Allergic Patients on Mammalian Meat Challenge.

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.

The epidemiology of food allergy in adults.

Warren C, Nimmagadda SR, Gupta R, Levin M
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.

Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome.

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.