Corn allergy is one form of food allergy that appears more prevalent than originally thought. Reports from the late 1950s suggested that corn allergy occurred in 0.16-30% of food allergy patients and were thought to be due to the sugars in corn.¹ Surveys in countries such as Pakistan and Mexico revealed that corn allergies may be as high as 1% of their populations.² A 2012 Milan study found that corn proteins, prolamins, contain amino acid sequence similar to those of wheat proteins and that some corn-allergic patients developed symptoms reminiscent of those of celiac disease.³

Despite the global prevalence of corn-allergy, very little research is currently available to address this class of food allergies.

Corn allergy vs. other common allergies

*Source: Prevalence and Severity of Food Allergies Among US Adults 

How does corn allergy develop?

Like other food allergies, corn allergy is manifested as an immune response when the body detects a harmful foreign substance or organism. Upon first encounter with the allergy-causing food such as corn, the body produces antibodies called immunoglobulins E (IgE). Interactions of these antibodies with the allergen (corn) releases pro-inflammatory mediators such as leukotrienes, histamines, and prostaglandins. Subsequent exposure causes the body to respond aggressively by intensely and rapidly producing allergy symptoms immediately or hours later after eating or just touching corn-containing foods or other consumer products.

Patients with corn allergy can immediately experience symptoms such as:

• Erythema (redness, flushing)
• Pruritis (itching)
• Uticaria (hives)
• Itching and blistering (oral cavity)
• Throat tightening
•  Atropic dermatitis (eczema)
• Abdominal pain

As the body’s immune system continues to react, corn allergy patients can encounter some delayed manifestations and may be felt several hours later. Examples are:

• Headache
• Migraine
• Fatigue
• Mood disturbances
• Joint and muscle pain
• Upper respiratory symptoms

Characteristics of corn allergens⁴

• They’re proteins bound to lipids and possibly to glycans.
• They can structurally mimic lipids, glycans or glycolipids.
• They can pose a risk at very low concentrations (accurate dose is not yet confirmed).
• They behave like pathogen-associated microbial patterns favoring receptor binding.

The three protein fractions suspected to be involved in corn allergy include:

• 16 k Dalton protein which has the potential to induce IgE antibodies and is often found in grass, wheat, barley and rice.
• 50 kD salt-unextractable protein that has been shown to be heat and peptic/pancreatic enzyme resistant.
• 9 kD protein lipid transfer protein (LTP) is cited often as the main culprit in corn allergy. It is found in other foods and is responsible for most food allergies. It is heat resistant and survives stomach acids and digestive enzymes. It can trigger immunological response when it encounters immune cells in the intestines. It cross-reacts with other allergens such as those in peach but not with those in barley or wheat (protein allergens from the same botanic family rarely cross-react and if they do are very hard to diagnose. Those that are structurally identical in unrelated plants may trigger allergy in individuals who are sensitized to only one of them).

Critical considerations for assessing the underlying causes of corn allergenicity:

Grain crops cultivation and handling
Grain crops have a complex supply chain. Soybeans and corn, for example, are often cultivated on same US Midwestern farms and at the same time of year. Harvesting both crops is done using the same equipment, transportation, storage, etc. which may cause cross-contamination.

Grain processing methods
Since food allergens are proteins, it is conceivable that their activity (allergenicity and binding to IgE antibodies) will be impacted by processing conditions such as heat, pressure, enzymes, presence of solutes, etc.

Dry milling of genetically modified corn, StarlinkTM (currently approved only for animal feed) can significantly reduce the concentration of Cry 9 protein (confers insecticidal activity on the corn plant) by 40%. Further processing to simulate tortilla chips production was reported to decrease the protein concentration to undetectable levels.⁵ Glycation or Maillard reaction can decrease the proteins’ IgE binding i.e. reduce its allergenicity potential.⁶

Diagnosis methods to confirm corn allergies include: 1) Detection of corn specific IgE antibodies in blood using skin prick test or immunoassays, 2) Double-blind, placebo-controlled food challenge (DBPCFC), and 3) Subjective skin test.

1. Detection of corn specific IgE levels in blood serum ⁷

Blood samples taken from allergy patients are tested in-vitro using enzyme-linked immunosorbent assays (ELIZA) or radioallergosorbent tests. The presence/absence of allergic reactions or their intensity are evaluated using the following standardized reference values:⁸

Class 1 or greater level of IgE antibodies in serum indicates an increased likelihood of allergenicity.

2. Double-blind, placebo-controlled food challenge (DBPCFC)

This is the most reliable food allergy test. According to the Utrecht Center for Food Allergy,9 the DBPCFC test is conducted in a hospital setting with trained nurses and available emergency staff. The patient is exposed to gradually increasing doses of the suspected food that is hidden in a matrix. The placebo is formulated using an identical matrix. The allergen-containing and placebo doses are given randomly to the patient and the challenge is discontinued when objective symptoms (urticaria, facial swelling, rhinoconjunctivitis, vomiting, diarrhea, dyspnea, bronchoconstriction) or subjective symptoms (oropharyngeal pain, nausea, and abdominal pain) are confirmed on at least 3 subsequent doses. The lowest dose that induces allergic reactions is called eliciting dose (ED). These symptoms are graded according to a scale adapted from the Mueller score for insect venom allergy.¹⁰

3. Subjective skin tests

This group of tests involves exposing the skin to the suspected allergen to assess signs of allergic reactions. Although they are widely used in identifying food allergies, they lack accuracy and allergen specificity. Skin testing is usually done at a doctor’s office and takes 20-40 minutes and may detect immediate or delayed allergic reactions.

Skin prick test: A skin prick test, also called a puncture or scratch test, checks for immediate allergic reactions to as many as 50 different substances at once. In adults, the test is usually done on the forearm while children are typically tested on the upper back. Small marks are drawn on the skin where a drop of the allergen extract is placed next to each mark using needles (lancets) to prick the extracts into the skin’s surface. About 15 minutes later, the skin is checked for signs of allergic reactions such as raised, red, itchy bumps (wheals). The size of the bump is considered an indication of the extent of allergenicity.

Skin patch test: Patch tests are conducted to check whether a particular substance is causing allergic skin inflammation (contact dermatitis). They can detect delayed allergic reactions, which can take several days to develop. The allergens are applied to patches, which are then placed on the skin. The patch is left on the arm or back for 48 hours. The development of skin irritation may indicate allergy.

It should be noted that skin tests are not always accurate and sometimes result in a false- positive. In other cases, skin testing may not trigger a reaction upon exposure to the allergen, i.e. a false-negative. Allergy patients may also react positively to a substance during a test but not react to it in everyday life.

Corn allergy treatment

Based on the patient’s diagnosis, the allergist or immunologist can design a treatment plan which may include:

•  Medications
•  Immunotherapy
• Dietary or environmental changes.

References

1. Howard, W.A., Todd, R. and Dalton, G. Studies on the allergenicity of corn products.  J. Allergy, 1959, 30, 5, pp 381-387.
2. Inam, M., Hamid, R., Roohi, N.,Irfan, M., Abbas, S. and Ismail, M. Prevalence of sensitization to food allergens and challenge proven food allergy in patients visiting allergy centers in Rawalpindi and Islamabad, Pakistan, 2016. Springerplus 5, 1, pp 1330. doi: 10.1186/s40064-016-2980-0.
3. Mickowska, B., Socha, P., Urminska, D. and Cieslik, E. 2012, the comparison of prolamins extracted from different varieties of wheat, barley, rye, and triticale species: amino acid composition, electrophoresis, and immunodetection. J. Microbiol. Biotechnol. Food Sci., 1, 4, pp 742-752.
4. Pastorello, E.A., Pompei, C., Pravettoni, V., Farioli, L., Calamari, A., Scibilia, J., Robino, A.M., Conti, A., Lametti, S., Fortunato, D., Bonomi, S. and Ortolani, C. Lipid-transfer protein is the major maize allergen maintaining IgE-binding activity after cooking at 100°C, as demonstrated in anaphylactic patients and patients with positive double-blind, placebo-controlled food challenge results, 2003. J. Allergy Clin. Immunol. 112, 4, pp 775-783.
5. Vissers, Y.M., Blanc, F., Skov, P.S., Johnson, P.E., Rigby, N.M., Pryzbylski-Nicaise, L., Bernard, H., Wal, J.-M., Ballmer-weber, B., Zuidmeer, L., Szepfalusi, Z., Ruinemans, J., Jansen, A., Savelkoul, H., Wichers, H., Mackie, A., Mills, C. and Adel-Patient, K. effect of heating and glycation on the allergenicity of 2S albumins (Ara h 2/6) from peanut. 2011.PLoS One, 6(8): e23998. doi: 10.1371/journal.pone.0023998.Di
6. az, C., Fernandez, C., McDonald, R. and Yeung, J.M. Determination of Cry9C protein in processed foods made with StarLink corn. JAOAC Int. 2002, 85, 5, pp 1070-1076.
7. Mayo Clinic, test ID: Corn-food, IgE, serum. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/82705. Accessed on July 29, 2021.
8. Homburger, H.A. and Hamilton, R.G. Chapter 55: Allergic Diseases. In Henry’s Clinical Diagnosis and Management by Laboratory methods, 23rd edition, RA McPherson and MR Pincus (Eds). Elsevier, 2017, pp 1057-1070.
9. Utrecht Center for Food Allergies. https://ucfa.nl/food-allergy/diagnostics/dbpcfc/
10. Mueller, H.L. Diagnosis, and treatment of insect sensitivity. J. Asthma Res. 1966, 3, pp 331-333. Doi:10.3109/02770906609106941.