A:

Thank you for your question.



Galactose-alpha-1-3 galactose may be present in products derived from non-primate mammals, including cows, pigs and sheep. Gelatin can stimulate a separate specific-IgE response but galactose-alpha-1-3 galactose also may be found in gelatin products, which may create confusion for patients (1). High fat foods derived from hoofed mammals, such as cream from cow’s milk, may be a problem. In addition, albumin and immunoglobulin sensitivity may explain reactions to both cow’s milk and beef. There are also reports of individuals who react to kidney or intestine ingestion but can tolerate meat. This is due to sensitivity to allergens other than gelatin or alpha-gal (2,3).



I have referred your question to Dr. Scott Commins, Associate Professor of the University of North Carolina at Chapel Hill. Dr. Commins has published many of the sentinel papers related to alpha-gal sensitivity.



Dr. Commins provided information that a variety of products with animal sources may contain alpha-gal in sufficient quantities to result in reactions. These products include tissue from animals such as porcine heart valves and bovine cartilage. Gelatin products may contain alpha-gal depending on process of producing. Foods made from high fat content milk, such as ice cream and whole cream, also may contain alpha-gal. Plasma expanders used in Europe and other parts of the world, such as polygeline (Haemaccel) and succinylated gelatin (Gelofusine) are also potential, albeit unlikely, sources of alpha-gal. The likelihood of reactions to such products is very remote but possible. Dr. Commins stressed the importance of animal fat content and indicated that most alpha-gal allergic individuals in his practice tolerate moderate, lean dairy exposure as well as gelatin capsules.



In summary, I think you can reassure your patients that the risk of reacting to the products mentioned is extremely unlikely but nevertheless possible. Informing your patient without creating increased anxiety is a challenge. However, I would not dismiss the possibility and if your patients are highly sensitive to alpha-gal, I would strongly encourage having self-administered epinephrine available.



1. Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose.

Mullins RJ, James H, Platts-Mills TA, Commins S

J Allergy Clin Immunol. 2012;129(5):1334. Epub 2012 Apr 3.

Background: We have observed patients clinically allergic to red meat and meat-derived gelatin.

Objective: We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test result, and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and galactose-α-1,3-galactose (α-Gal).

Methods: Adult patients evaluated in the 1997-2011 period for suspected allergy/anaphylaxis to medication, insect venom, or food were skin tested with gelatin colloid. In vitro (ImmunoCAP) testing was undertaken where possible.

Results: Positive gelatin test results were observed in 40 of 1335 subjects: 30 of 40 patients with red meat allergy (12 also clinically allergic to gelatin), 2 of 2 patients with gelatin colloid-induced anaphylaxis, 4 of 172 patients with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02-0.4 g), and 4 of 368 patients with drug allergy. Test results were negative in all patients with venom allergy (n = 241), nonmeat food allergy (n = 222), and miscellaneous disorders (n = 290). ImmunoCAP results were positive toα-Gal in 20 of 24 patients with meat allergy and in 20 of 22 patients with positive gelatin skin test results. The results of gelatin skin testing and anti-α-Gal IgE measurements were strongly correlated (r = 0.46, P<.01).α-Gal was detected in bovine gelatin colloids at concentrations of approximately 0.44 to 0.52μg/g gelatin by means of inhibition RIA.

Conclusion: Most patients allergic to red meat were sensitized to gelatin, and a subset was clinically allergic to both. The detection ofα-Gal in gelatin and correlation between the results ofα-Gal and gelatin testing raise the possibility thatα-Gal IgE might be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat,α-Gal, and gelatin (with or without clinical reactivity) remains uncertain.



2. Alimentary allergy to pork. Crossreactivity among pork kidney and pork and lamb gut.

Llátser R, Polo F, De La Hoz F, Guillaumet B

Clin Exp Allergy. 1998;28(8):1021.

Background: A patient suffered from anaphylaxis after the ingestion of pork gut and kidney, but she tolerated pork meat. Clinical symptoms were also triggered upon intake of lamb gut.

Objective: To demonstrate an IgE-mediated hypersensitivity and identify the pork proteins involved. And also, to study the possible cross-allergenicity among proteins from lamb gut and pork.

Methods and Results: The patient had strong positive skin-prick test responses to pork kidney, gut and liver, and lamb gut and kidney. RAST technique showed specific IgE to pork kidney, gut and meat. Immunoblotting after SDS-PAGE disclosed the presence of four prominent IgE-binding polypeptides in pork kidney (200, 90, 57, and 47 kDa), two in gut (57 and 27 kDa), and three in meat (51, 40, and 28-30 kDa), apart from other weaker radiostained bands in each extract. The binding of IgE to 200 and 90 kDa allergens from pork kidney was inhibited by gut from pork and lamb in immunoblotting inhibition assays. No inhibition was produced by pork meat.

Conclusions: A mechanism of IgE-mediated hypersensitivity has been demonstrated in this case of anaphylaxis provoked by pork products. Four main allergens were detected in pork kidney, two of which (200 and 90 kDa) share allergenic epitopes with proteins from pork and lamb gut. On the other hand, pork meat does not seem to have allergenic epitopes in common with pork kidney.



3. TIgE antibody response to vertebrate meat proteins including tropomyosinAyuso R, Lehrer SB, Tanaka L, Ibañez MD, Pascual C, Burks AW, Sussman GL, Goldberg B, Lopez M, Reese G

Ann Allergy Asthma Immunol. 1999;83(5):399.

Background: Although meat is a main source of proteins in western diets, little information is available regarding allergy to vertebrate meats or the allergens implicated in these reactions.

Objective: To evaluate the in vitro IgE antibody response to different vertebrate meats in suspected meat-allergic subjects, as well as the possible role of tropomyosin in meat allergy and to analyze the cross-reactivity between vertebrate meats and the effect of heating on the IgE-binding to meat proteins.

Methods: Fifty-seven sera from suspected meat-allergic subjects were tested by grid blot to extracts of beef, lamb, pork, venison, chicken, and turkey and to four mammalian tropomyosins of different origins.

Results: Meat-allergic subjects have IgE antibodies to proteins in different mammalian meats (43/57 subjects); cross-reactivity with avian meat was limited: less than 50% (19/43) of meat positive sera reacted to chicken. In contrast, most of the poultry-positive sera also reacted to different mammalian meats. In general, there was stronger IgE reactivity to raw meats in comparison to cooked meats; an exception was six cases in which IgE reactivity to cooked poultry was stronger. Weak IgE reactivity to tropomyosin was detected in only 2/57 sera tested.

Conclusions: Suspected meat-allergic subjects have serum IgE directed to meat proteins. In vitro cross-reactivity among mammalian meats appears to be important, while cross-reactivity to poultry is limited indicating mammalian-specific proteins. Although cooking in general denatures meat proteins rendering them less allergenic, in some cases the process of cooking may result in the formation of new allergenic moieties. The muscle protein tropomyosin is not an important vertebrate meat allergen.



I hope this information is of help to you and your patient.



All my best.

Dennis K. Ledford, MD, FAAAAI

