True or pollen-associated fruit allergy?

Summer is calling - pollen-associated food allergy awaits many of us.

Molecular diagnosis is essential for the management and risk assessment of patients struggling with fruit allergy or pollen-related fruit allergy. The most important clinical task regarding fruit allergies is to identify the allergenic molecules and to screen out patients who are at high risk for systemic reactions.

Correct diagnosis of fruit allergies is not always easy and can be challenging. In fact, cross-reactive proteins can complicate the diagnosis of fruit allergy, as they can cause clinically irrelevant positive tests for cross-reactive foods. Therefore, molecular tests that include both cross-reactive components and primary food allergens are an important tool for precise diagnosis as well as dietary recommendations.

What comes first?

Depending on the sensitisation pathway, fruit allergy is either the result of a true primary food allergy or a secondary pollen-associated food allergy.

Primary food allergy often occurs in infancy. Sensitisation results from direct contact of the allergens with the gastrointestinal mucosa. This includes, above all, lipid transfer protein syndrome (LTP syndrome), which can trigger mild to severe systemic reactions and even anaphylaxis. Thaumatin-like protein (TLP) has also been identified as a true food allergen. This has been described in various fruits such as apple (Mal d 2) and kiwi (Act d 2) for instance. (1, 2) These allergens are very stable to heat and retain their structure in the gastrointestinal tract, a property that is essential for the potential to sensitise and trigger allergic reactions. In kiwifruit allergy, actinidin (Act d 1) and a glycoprotein (Act d 3) have been identified as potential marker allergens for severe symptoms. (3, 4)

Secondary food allergy mainly affects older children, adolescents and adults who are diagnosed with pollen allergy and consequently react to cross-reactive food allergens in fruits.

In pollen-fruit syndrome, the fruit allergy results from primary sensitisation to labile pollen allergens, such as profilins and PR-10 proteins (Bet v 1 homologues) and the resulting phenotype is usually mild and consists of local reactions, such as oral allergy syndrome (OAS). Symptoms typically include redness, mild swelling or itching of the lips, mouth, throat and ears. Occasionally, symptoms may also occur in the oesophagus or stomach, causing abdominal pain, nausea and even vomiting. Sneezing, runny nose or eye symptoms may also occur.

Although much less common, severe fruit allergies may also be associated with latex (latex-fruit syndrome). Cross-reactions to foods are also known to occur in latex allergy. Since some proteins in fruits or vegetables are similar in structure to pollen or latex allergens, affected patients can subsequently also react allergically when eating the corresponding foods. As a result of latex-fruit syndrome, up to 88% of latex-allergic adults have specific IgE to plant foods. Several homologous proteins are present in both allergenic plant foods and latex, including Hev b 2 (β-1,3-glucanase), Hev b 11 (class I chitinase) and Hev b 8 (profilin). Hev b 6 (prohevein) is the latex allergen that has received the most attention as a possible cause of latex fruit allergy syndrome.

Fruit allergens

Molecular allergy diagnostics using apple as an example: Mal d 1 is the related allergen to birch pollen Bet v 1. Mal d 1 is susceptible to heat and digestion. Those who only have IgE to Mal d 1 can tolerate cooked or baked apples and "only" have an oral allergy syndrome when eating raw apples. This is not the case with Mal d 3. Patients with IgE against Mal d 3 are "real" apple allergy sufferers. Here, severe systemic reactions are possible, even against heat-treated apples.

In general, food allergens are divided into class I and II allergens.

Class I proteins are very stable allergens that withstand thermal treatment and enzymatic digestion. They remain stable even in cooked as well as baked form, can sensitise the person via the gastrointestinal tract and are therefore considered true food allergens that can trigger primary (non-pollen related) sensitisation and cause clinical reactions up to anaphylaxis. These include the lipid transfer proteins (LTPs) in apple (Mal d 3), strawberry (Fra a 3), kiwi (Act d 10), peach (Pru p 3) and grape (Vit v 1). (5, 6) Pru p 3 has been identified as an important marker allergen of LTP allergy and therefore serves as a useful molecule in molecular allergy diagnostics. (7)

In contrast, class II food allergens are homologous proteins to other pollen proteins. Proteins that cause pollen-fruit syndrome are often altered by heating or stomach acid, are easily degraded, digestible, heat-labile and result in milder, local symptoms such as oral allergy syndrome. Class II food allergy develops as a result of primary sensitisation to respiratory allergens via cross-reactivity. Most sufferers of pollen-food syndrome experience allergy symptoms when they eat fruits raw, but can eat the same foods without problems when they are cooked. Primary sensitisation to profilins (e.g. Bet v 2 in birch or Phl p 12 in grass pollen) often results in cross-reactions with apple (Mal d 4), peach (Pru p 4), cherry (Pru av 4), grape (Vit v 4), melon (Cuc m 2) and strawberry (Fra a 4). PR-10 proteins (Bet v 1 homologues) are found in apple (Mal d 1), peach (Pru p 1), cherry (Pru av 1), grape (Vit v 8) and strawberry (Fra a 1). The Bet v 1 homologous proteins from hazelnut, celery and peanut/soybean were shown to be more heat resistant than the proteins from fruits of the Rosaceae family in some studies. This may explain why they sometimes cause more severe systemic reactions in Bet v 1-associated food allergy.

ALEX

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References

  1. doi: 10.1159/000144036
  2. doi: 10.1002/mnfr.200700167
  3. doi: 10.1111/j.1365-2222.2007.02927.x
  4. doi: 10.1097/ACI.0b013e3283464c74
  5. doi: 10.18176/jiaci.0110
  6. doi: 10.1111/cea.13053
  7. doi: 10.1111/all.13151