Allergenicity of Carbohydrates and Their Role in Anaphylactic Events
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The IgE response to pollen allergens often includes IgE antibodies specific for glycosylation motifs on the pollen proteins. These oligosaccharides are present on many different species and are known as cross-reactive carbohydrate determinants. However, IgE antibodies to plant-derived cross-reactive carbohydrate determinants seem to have only minor clinical significance and have not been related to anaphylaxis. Recently, two novel forms of anaphylaxis have become apparent in the southeastern United States: 1) reactions during the first infusion of the monoclonal antibody cetuximab and 2) adult-onset delayed anaphylaxis to red meat. Detailed investigation of serum antibodies established that in both cases, the patients had IgE antibodies specific for the mammalian oligosaccharide galactose alpha-1, 3-galactose. Identification of these cases is helpful in avoiding infusion reactions to cetuximab or recommending specific avoidance of meat derived from mammals. However, the current evidence does not fully resolve why these IgE antibodies are so common in the Southeast or why the anaphylactic or urticarial reactions to red meat are delayed.
KeywordsAnaphylaxis Oligosaccharides Cross-reactive Carbohydrate Determinants Red Meat IgE to Alpha-Gal
Dr. Platts-Mills has received grant support from the National Institutes of Health (A120565).
Dr. Platts-Mills has received grant support from Phadia AB. No other potential conflicts of interest relevant to this article were reported.
Papers of particular interest, published recently, have been highlighted as follows: •Of importance ••Of major importance
- 3.• Jefferis R: Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov 2009, 8:226–234. This is an excellent account of the mechanisms of glycosylation of proteins and recombinant proteins. This article provides a background for understanding that these therapeutic molecules can include an antigenic/allergenic epitope that was not predicted by the amino acid sequence. CrossRefPubMedGoogle Scholar
- 5.•• Chung CH, Mirakhur B, Chan E, et al.: Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 2008, 358:1109–1117. These studies defined for the first time IgE antibodies specific for a mammalian oligosaccharide that was previously well known as a transplantation barrier: alpha-gal. These IgE antibodies were first identified in sera from patients who had a severe hypersensitivity reaction to the monoclonal antibody cetuximab. The evidence argues that these reactions occur because the monoclonal antibody has alpha-gal on the Fab portion of the heavy chains. CrossRefPubMedGoogle Scholar
- 7.•• Commins SP, Satinover SM, Hosen J, et al.: Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2009, 123:426–433. This article reports on 24 patients with delayed anaphylaxis to red meat. There are several striking features of these patients. First, they are predominantly in the Southeast; second, the patients have very weak reactions to skin tests with beef or pork but are positive to intradermal skin tests. In most cases, the specificity of their serum IgE antibodies correlates with the species of meat to which they react (ie, beef, pork, and lamb but not chicken, turkey, or fish). CrossRefPubMedGoogle Scholar
- 8.•• O’Neil BH, Allen R, Spigel DR, et al.: High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol 2007, 25:3644–3648. O’Neil and colleagues documented a remarkable prevalence of acute hypersensitivity reactions to the monoclonal antibody cetuximab. They collaborated with colleagues in Tennessee, and the prevalence was about 20% in both states. They also reported that reactions to the same monoclonal were not occurring or were rare in northern states (ie, ≤ 1%). CrossRefPubMedGoogle Scholar
- 9.Owera R, Gill A, Haddadin R, et al.: High incidence of hypersensitivity reactions to cetuximab infusions in mid-Missouri: association with prior history of atopy [abstract]. 2008 American Society of Clinical Oncology Annual Meeting Proceedings. Columbia, MO: American Society of Clinical Oncology; 2008:20747.Google Scholar
- 10.Qian J, Liu T, Yang L, et al.: Structural characterization of n-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption/ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzymatic digestion. Anal Biochem 2007, 364:8–18.CrossRefPubMedGoogle Scholar
- 14.Ishihara H, Takahashi N, Oguri S, Tejima S: Complete structure of the carbohydrate moiety of stem bromelain. An application of the almond glycopeptidase for structural studies of glycopeptides. J Biol Chem 1979, 254:10715–10719.Google Scholar
- 18.•• Jacquenet S, Moneret-Vautrin DA, Bihain BE: Mammalian meat-induced anaphylaxis: clinical relevance of anti-galactose-alpha-1,3-galactose IgE confirmed by means of skin tests to cetuximab. J Allergy Clin Immunol 2009, 124:603–605. This brief report provides detailed documentation of three cases seen in the Lorraine region of France. What is important is that they define the specificity very clearly and show that the pork-cat syndrome is distinct from delayed anaphylaxis in patients with IgE to alpha-gal. The pork-cat syndrome is related to IgE antibodies to cat albumin that cross-react with pork albumin. CrossRefPubMedGoogle Scholar
- 29.Mortimer BC, Beveridge DJ, Martins IJ, Redgrave TG: Intracellular localization and metabolism of chylomicron remnants in the livers of low density lipoprotein receptor-deficient mice and apoE-deficient mice. Evidence for slow metabolism via an alternative apoE-dependent pathway. J Biol Chem 1995, 270:28767–28776.CrossRefPubMedGoogle Scholar
- 31.Greenberger PA: Idiopathic anaphylaxis. Immunol Allergy Clin North Am 2007, 27:273–293, vii–viii.Google Scholar
- 34.Boodman SG: Was it a sudden seafood allergy? No. Washington Post. October 20, 2009:1E, 6E.Google Scholar