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Mammalian allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tuomas Virtanen, Marja Rytkönen-Nissinen
Animal-allergic patients may have IgE antibodies against a number of serum albumins, such as Fel d 2, Can f 3, and Equ c 3. Inhibition experiments show that albumin-specific IgE is often cross-reactive, although patients exhibit individual variation in this respect [118,164]. As pointed out for Fel d 2, the primary sensitizer can be difficult to identify [59], but component-resolved diagnostics can help in this respect. A study with three tryptic peptides from horse serum albumin identified regions involved in IgE cross-reactivity with dog albumin [165]. Inhibition of a monoclonal anti–human albumin antibody with cat or dog albumin suggests that cat, dog, and human albumins have similar epitopes [55]. In another study, monoclonal antibodies specific to cat or dog albumin recognize the albumin of both species [166]. The study also suggests that the monoclonal antibodies and human IgE recognize identical or closely related epitopes on cat and dog albumin. Moreover, the IgE responses of animal-allergic subjects to Fel d 2, Can f 3, and Equ c 3 correlate significantly [163]. Although the clinical significance of albumins in respiratory allergy still needs further clarification, albumin allergy, particularly in an occupational exposure, can be a significant cause of disease. Moreover, respiratory sensitization to cat epithelium containing Fel d 2 may lead to pork-cat syndrome in which IgE cross-reactivity between albumins leads to hypersensitivity symptoms upon ingestion of pork meat containing pork albumin [167].
Mammalian Allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2014
Tuomas Virtanen, Tuure Kinnunen, Marja Rytkönen-Nissinen
Animal-allergic patients may have IgE antibodies against a number of serum albumins, such as Fel d 2, Can f 3, and Equ c 3. Inhibition experiments show that albumin-specific IgE is often cross-reactive although patients exhibit individual variation in this respect.82,116 As pointed out for Fel d 2, the primary sensitizer can be difficult to identify.41 A study with three tryptic peptides from horse serum albumin identified regions involved in IgE cross-reactivity with dog albumin.117 Inhibition of a monoclonal antihuman albumin antibody with cat or dog albumin indicates that cat, dog, and human albumins have similar epitopes.40 In another study, monoclonal antibodies specific to cat or dog albumin recognized the albumin of both species.118 The study also suggests that the monoclonal antibodies and human IgE recognize identical or closely related epitopes in cat and dog albumin. In all, it seems that although the clinical significance of albumins in respiratory allergy is unclear, they only occasionally (e.g., in an occupational exposure) can be a significant cause of allergy. Instead, respiratory sensitization to cat epithelium containing Fel d 2 may lead to pork-cat syndrome in which IgE cross-reactivity between albumins leads to hypersensitivity symptoms upon ingestion of pork meat.119
Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients
Published in Expert Review of Clinical Immunology, 2020
In terms of diagnosis, skin prick tests with extracts of mammalian meats (beef, pork, or lamb) were shown to be unreliable [1]. The majority of providers rely on commercially available blood testing for alpha-gal IgE that is widely available in the US (via Viracor-Eurofins) and Europe (via Phadia ThermoFisher). If skin testing is preferred, sensitization can be investigated using intradermal (ID) skin tests to the same diluted food extracts [1]; however, several reports suggest ID testing with gelatin may produce more consistent results [14,17,19]. One alternative is prick-prick skin testing using cooked meats – this approach has produced consistent, albeit small (5–7 mm), wheals, and should properly include a non-mammalian meat as well [1,19]. If beef is the only positive meat by prick-prick testing, a diagnosis of cow’s milk allergy must be ruled out since beef reactivity can occur in a minority of cow’s milk allergic patients [20]. Differentiating AGS from ‘traditional’ cow’s milk allergy can be accomplished efficiently with serum IgE testing for alpha-gal and cow’s milk components (e.g. casein, whey) [15]. There are no established criteria for the titer of alpha-gal IgE that confirms an AGS diagnosis and most clinical authorities report using the cutoff of >0.1 IU/mL as a positive test result, which has a reported specificity of 92.3% and sensitivity of 100% among patients with AGS [6,16,21]. Diagnosis is particularly challenging in patients with a history of reacting to mammalian products but whose blood test for alpha-gal IgE is negative. In our clinical experience, this occurs in approximately 2% of patients referred for AGS evaluation. Not uncommonly, we assess surrogate markers (beef, pork, lamb) by skin and serum IgE testing in these patients. When AGS diagnosis is in doubt due to negative IgE testing, it would be reasonable to test for IgE to cat serum albumin (Fel d 2) to identify patients who may have pork-cat syndrome. Similarly, clinicians could consider testing for IgE to gelatin – both porcine and bovine. As a referral center, we also perform skin testing to alpha-gal-containing biologics such as cetuximab and basophil activation testing. These approaches have led to diagnostic clarification in 41 of 52 (78%) patients with alpha-gal IgE seronegative testing who report compelling symptoms. For those remaining patients with uncertain diagnoses, we offer blinded food challenges using pork and emu sausages on two different occasions. Longitudinal data of patients with AGS suggest that alpha-gal IgE declines over time; additional tick bites, however, appear to lead to rises in alpha-gal IgE [7,16]. Thus, another possible reason for seronegative testing despite a history of symptoms is that a patient’s alpha-gal IgE has declined below the limit of test detection yet remains clinically relevant. Since IgE on the surface of mast cells may persist for months, it is conceivable that undetectable serum levels can occur in the setting of allergen-primed mast cells.