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Журнал "Гастроэнтерология" Том 57, №4, 2023

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Гастроінтестинальні прояви, спектр та частота сенсибілізації до харчових алергенів у дорослих жителів м. Києва з алергічним ринітом: крос-секційне дослідження

Гастроінтестинальні прояви, спектр та частота сенсибілізації до харчових алергенів у дорослих жителів м. Києва з алергічним ринітом: крос-секційне дослідження

Авторы: V.V. Tsaryk, A.V. Neverovskyi, V.Р. Shypulin
Bogomolets National Medical University, Kyiv, Ukraine

Рубрики: Гастроэнтерология

Разделы: Клинические исследования

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Резюме

Актуальність. Харчова алергія вражає 1–3 % дорослих у всьому світі. Понад 160 харчових продуктів можуть викликати алергічні реакції. Харчова алергія може передувати алергічному риніту і стимулювати його. Метою роботи було оцінити спектр та частоту сенсибілізації до харчових алергенів у пацієнтів із встановленим алергічним ринітом із м. Києва (Україна). Матеріали та методи. Дослідження проводилося як крос-секційне. У нього було залучено 175 дорослих мешканців м. Києва з алергічним ринітом. Сенсибілізацію до алергенів та їх компонентів визначали за допомогою шкірних прик-тестів та виявлення in vitro алергенспецифічних IgE в сироватці крові методом імуноферментного аналізу (багатокомпонентний тест Allergy Explorer2 ALEX2). Результати. Було виявлено, що переважає сенсибілізація до таких інгаляційних алергенів: тимофіївки — у 50,3 %, амброзії — у 48,6 %, берези — у 44 %, полину — у 24 %, плісняви Alternaria alternata — у 15,4 % хворих. Косенсибілізацію хоча б до одного харчового алергену зареєстровано в 131 (74,9 %) пацієнта, із них 77 (58,8 %) мали гастроінтестинальні симптоми. Переважала сенсибілізація до наступних харчових алергенів: фундука — 27,5 % випадків, яблука — 26,3 %, арахісу — 21,7 %, селери — 14,3 %, сої — 13,1 %, коропа — 11,4 %, ківі — 9,1 %, краба — 9,1 %, тріски — 8,6 %, устриці — 8,6 %, персику — 8 %, лобстера — 8 %, моркви — 7,4 %, анізакід — 6,3 %, креветки — 6,3 %, тигрової креветки — 5,7 %, яловичини — 5,1 %. Частота сенсибілізації до перехресно-реактивних білків PR-10 становила 20,5 % (95% довірчий інтервал (ДІ) 9,7–33,9 %) у пацієнтів з алергічним ринітом без харчової косенсибілізації порівняно з 51,1 % (95% ДІ 42,5–59,7 %) в учасників з алергічним ринітом і супутньою харчовою сенсибілізацією, p < 0.001; до nsLTP — відповідно 2,3 % (95% ДІ 0–8,9 %) і 19,8 % (95% ДІ 13,4–27,2 %), p = 0,011. Висновки. Серед дорослих пацієнтів з алергічним ринітом, які мешкають у м. Києві, приблизно три чверті мають харчову косенсибілізацію, що може бути причиною гастроінтестинальних симптомів і загострень алергічного риніту після вживання овочів, фруктів та горіхів через перехресну реакцію з інгаляційними алергенами. Це слід враховувати при лікуванні таких хворих.

Background. Food allergy affects 1–3 % of adults worldwide. More than 160 foods can cause allergic reactions. Food allergy may precede and stimulate allergic rhinitis. Aim of the study was to assess the spectrum and frequency of sensitization to food allergens in patients with allergic rhinitis from Kyiv, Ukraine. Materials and me­thods. The investigation was conducted as a cross-sectional study. One hundred and seventy-five Kyiv adult patients with allergic rhinitis were enrolled in the trial. Sensitization to allergens and their components was determined by skin prick tests and in vitro detection of allergen specific IgE by ELISA in blood serum — a multicomponent Allergy Explorer2 ALEX2 test. Results. It was shown that sensitization to following inhalant allergens was predominant: to timothy grass — in 50.3 %, to ragweed — in 48.6 %, to birch — in 44 %, to wormwood — in 24 %, to Alternaria alternata mold — in 15.4 % of patients. One hundred and thirty-one (74.9 %) participants have co-sensitization to at least one food allergen, among them 77 (58.8 %) had gastrointestinal symptoms. Sensitization to following food allergens was predominant: to hazelnut — 27.5 %, apple — 26.3 %, peanut — 21.7 %, celery — 14.3 %, soy — 13.1 %, carp — 11.4 %, kiwi — 9.1 %, crab — 9.1 %, codfish — 8.6 %, oyster — 8.6 %, peach — 8 %, lobster — 8 %, carrot — 7.4 %, anisakis — 6.3 %, prawn — 6.3 %, tiger prawn — 5.7 %, to beef — 5.1 % of cases. It was found that the frequency of sensitization to cross-reactive proteins PR-10 was 20.5 % (95% confidence interval (CI); 9.7–33.9 %) in patients with allergic rhinitis without food co-sensitization comparing to 51.1 % (95% CI; 42.5–59.7 %) in participants with both allergic rhinitis and food co-sensitization, p < 0.001; to nsLTP — 2.3 % (95% CI; 0–8.9 %) and 19.8 % (95% CI; 13.4–27.2 %), respectively, p = 0.011. Conclusions. Among Kyiv adult patients with allergic rhinitis, approximately three quarters have food co-sensitization that may be the cause of gastrointestinal symptoms and exacerbations of allergic rhinitis after consuming vegetables, fruits and nuts due to cross-reactivity with inhalant allergens. This should be considered when manage such patients.


Ключевые слова

харчова алергія; алергічний риніт; перехресна реактивність

food allergy; allergic rhinitis; cross-reactivity

doi: http://dx.doi.org/10.22141/2308-2097.57.4.2023.565

Introduction

Food allergy (FA) affects 1–3 % of adults and 4–6 % of children under 6 years. More than 160 foods can cause allergic reactions [1, 2]. IgE-mediated food allergy is a serious human health problem affecting 1 to 10 % of the population in developing countries, with variability depending on geographi–cal area and age range [3]. Allergic reactions can range from mild itching to anaphylactic shock. Typically, food allergies include both IgE- and non-IgE-mediated immune disorders that occur after exposure to a food allergen. Although non-IgE-mediated food allergies correspond to pathological conditions of specific tissues, involving antigen-specific T cell responses (e.g., celiac disease), IgE-mediated allergies have various manifestations, including mild itching, gastrointestinal symptoms, and dangerous systemic anaphylaxis reactions [4].
In most cases, allergies are caused by the so-called major food allergens — “big 8”: peanuts, milk, eggs, soy, wheat, fish, shellfish and nuts. These ingredients must be properly labeled in accordance with the Food and Drug Administration (FDA) [5], and the EU allergen labeling requirements provide for 14 allergens: wheat, crustaceans, eggs, fish, peanuts, soy, milk, nuts, celery, mustard, sesame seeds, lupines, mollusks, sulfites with a concentration of more than 10 mg/kg [6]. It is worth mentioning that allergens can be incorporated into food ingredients at the level of traces, provoking possible discrepancies between food content and labeling. In addition, a wide range of isoforms and posttranslational modifications (PTMs), as well as structural changes during processing can determine the allergenicity of proteins [7–9].
IgE-mediated FA affects approximately 3 % of the po–pulation and has a strong impact on the daily lives of patients — the manifestations occur not only in the gastrointestinal tract, but also in other systems and organs. Studies have shown that food allergies coexist and are associated with an increase in the severity of asthma, allergic rhinitis and atopic dermatitis, which indicates that FA contributes to the chroni–city and severity of allergic diseases. Eggs (2.7 %), fish (1.6 %), shellfish (1.3 %), peanuts (1.3 %) and tree nuts (1.2 %) are the most commonly reported food allergens [4, 10, 11].
Cohort studies have shown that sensitization to food allergens develops in early childhood. The term “allergic sensitization” describes the induction of an allergic immune response at the first encounter with an allergen. There are different ways of allergic sensitization for FA [12]. The first way (e.g., for milk, eggs), that is characteristic of oral allergens, in which sensitization occurs through the gastrointestinal tract. The second way (e.g., for the main allergen of birch pollen Bet v1), that is characteristic of aeroallergens, in which sensitization occurs in the respiratory tract and creates the preconditions for the development of cross-reactions with homologous food allergens (e.g., with the main allergen of apples Mal d1). As a result, symptoms are present in both the gastrointestinal tract and respiratory tract [13]. The third way (so far research has been conducted only for peanuts) is percutaneous [14].
The aim of the present study was to assess the spectrum and frequency of sensitization to different food allergens in patients with established allergic rhinitis from Kyiv, Ukraine.

Materials and methods

Present clinical trial was performed in accordance with the Ukrainian laws, the requirements of Good Clinical Practice, and ethical principles of the Declaration of Helsinki. Written informed consent for participation in the study was obtained from all participants before beginning of investigation. The trial protocol was approved by the Bioethical Committee of Bogomolets National Medical University, Kyiv, Ukraine.
Study population. Participants were of both sexes, aged 18–69 years, with diagnosed allergic rhinitis. The inclusion criteria were: men and women, age 18–70 years, confirmed allergic rhinitis according to recommendations of ICAR-Allergic Rhinitis 2018 [15], no previous intake of antihistamines and glucocorticoids more than 4 weeks before participation in the investigation, a negative pregnancy test for women of reproductive age and signed informed consent. The exclusion criteria were: administration of any antihistamines and/or glucocorticoids for 4 weeks before the study, pregnancy and lactation, any acute diseases within 4 weeks before the trial, alcohol abuse, participation in other investigations.
Study design. The investigation was conducted as a cross-sectional study. A total of 175 participants with allergic rhinitis were selected to the study between the February 2021 to January 2022 on the basis of Department of clinical immunology and allergology with the section of medical genetics and Department of internal medicine 1 of Bogomolets National Medical University, Kyiv, Ukraine. All participants were the Kyiv citizens. 
Sensitization to allergens and their components was determined by skin prick tests (SPT) (Inmunotek, Spain) and in vitro detection of allergen specific IgE (sIgE) by ELISA in serum of the blood — multicomponent Allergy Explorer2 ALEX2 test (MacroArray Diagnostics, Vienna) allowing to detect sIgE to 295 allergens. The patient is considered sensitized to allergen in case of exceeding reference level of sIgE to at least one allergen extract or component (for example, Bet v1 in birch allergy).
Statistical analysis of the data was performed using SPSS software (version 23, IBM Corp., Armonk, NY, USA). The chi-squared test was used to determine the differences between expected frequencies. The difference was considered statistically significant at p < 0.050.

Results

The average age of participants was 33 years, men were 94 (53.7 %), women were 81 (46.3 %). 85 patients (48.6 %) pointed out on at least one gastrointestinal (GI) symptom after consuming the different food allergens (nuts, fruits, vegetables, fish and seafood, meat). The most common GI symptoms were nausea, vomiting, abdominal pain and diarrhea (Table 1).
Rates of sensitization to inhalant and food allergens. It was shown that sensitization to following inhalant allergens was predominant: to timothy grass — in 50.3 % of patients, to ragweed — in 48.6 %, to birch — in 44 %, to wormwood — in 24 %, to Alternaria alternata mold — in 15.4 % of patients (Table 2, Fig. 1).
In present study we revealed that 131 (74.9 %) partici–pants have co-sensitization to at least one food allergen, while 44 (25.1 %) patients weren’t sensitized to any of the food allergens (from 154 food allergen extracts and components tested in this study). It was shown that sensitization to following food allergens was predominant: to hazelnut — in 27.5 % of patients, to apple — in 26.3 %, to peanut — in 21.7 %, to celery — in 14.3 %, to soy — in 13.1 %, to carp — in 11.4 %, to kiwi — in 9.1 %, to crab — in 9.1 %, to codfish — in 8.6 %, to oyster — in 8.6 %, to peach — in 8 %, to lobster — in 8 %, to carrot — in 7.4 %, to anisakis — in 6.3 %, to prawn — in 6.3 %, to tiger prawn — in 5.7 %, to beef — in 5.1 %, to others — less than 5 % (Table 3, Fig. 2).
Among the patients with co-sensitization to food allergens, 77 (58.8 %) had GI symptoms, while among the participants without it, only 8 (18.2 %) had GI complaints, p < 0.001.
Additionally, to look for the possible difference between sensitization profiles of patients with only allergic rhinitis and patients with allergic rhinitis and co-sensitization to food allergens, we assessed sensitization to cross-reactive proteins, that are present in different allergen extracts and components, both inhalant and food. The following cross-reactive proteins have been assessed: PR-10 and nsLTP (Table 4). It was found that the frequency of sensitization to:
— PR-10 was 20.5 % (95% CI; 9.7–33.9 %) in patients with allergic rhinitis without sensitization to any food allergen comparing to 51.1 % (95% CI; 42.5–59.7 %) in parti–cipants with both allergic rhinitis and food co-sensitization, p < 0.001;
— nsLTP was 2.3% (95% CI; 0–8.9 %) in patients with allergic rhinitis without sensitization to any food allergen comparing to 19.8 % (95% CI; 13.4–27.2 %) in participants with both allergic rhinitis and food co-sensitization, p = 0.011.

Discussion

The results of present study shown that in Kyiv adult population with allergic rhinitis the sensitization to timothy grass, ragweed, birch, wormwood and Alternaria alternata mold was predominant and probably play causative role in development of seasonal allergic rhinitis exacerbations with corresponding clinical symptoms and features. Moreover, it was revealed in our investigation, that approximately three quarters of patients with allergic rhinitis also had co-sensitization to food allergens. The sensitization to hazelnut, apple, peanut, celery, soy, carp was predominant. Additionally, we revealed higher rates of GI symptoms in patients with such co-sensitization to food allergens.
According to some authors, the prevalence of food sensitization among patients with allergic diseases is 37 % and it does not differ significantly depending on gender or allergic disease. And the most common allergic disease among adults is allergic rhinitis — 59 % [16]. It has also been shown that women are more prone to allergic rhinitis associated with food allergies than men [17].
In fact, allergic rhinitis is a rare manifestation of food allergies. It may be associated with a primary food allergy; however, it is more commonly associated with secondary food allergies, also known as pollen food syndrome (PFS) [18]. Thus, some vegetables and fruits can cause IgE-mediated food allergies (rice, citrus fruits, black lentils and bananas are identified as the main allergens that induce symptoms of allergic rhinitis), and others can cause symptoms of allergic rhinitis due to similarity in structure or homology with pollen. It has been shown that 17 % of patients with pollen allergy (ie trees, weeds and grasses) may have a type I allergic reaction to certain vegetarian foods containing fruits and vegetables [17, 18].
PFS is usually a mild type of food allergy that occurs when the mouth and throat come into contact with raw fruits or vegetables that contain epitopes that are also present in the pollen to which the subject is sensitized. Usually when these products are prepared or processed, they can be consumed without consequences in form of allergic symptoms. Common symptoms of PFS are redness, mild swelling or itching of the lips, tongue, inside of the mouth, soft palate and ears, itching and mild swelling of the throat. Sometimes people may experience symptoms in the esophagus or stomach: abdominal pain, nausea and even vomiting. Symptoms of allergic rhinitis may also include sneezing, runny nose, or, less commonly, allergic conjunctivitis [19]. The most typical example of PFS is the development of oral symptoms when eating apples, hazelnuts, celery, and so on in patients with allergic rhinitis caused by birch pollen due to cross-reacti–vity. Other examples include hypersensitivity to wormwood, accompanied by symptoms after eating vegetables such as cabbage, cumin, parsley, coriander, anise and carrots, as well as some spices such as anise, pepper, black pepper, onion, garlic, cauliflower and broccoli. Maple pollen, hazelnut, peanut, fruits such as kiwis and peaches, and vegetables such as corn and lettuce, provoke allergic rhinitis symptoms in sensitive people after ingestion. Hypersensitivity to herbs and their classes, as well as their homology with other fruits, has not been studied in detail, but people who are sensitive to herbs are also sensitive to foods such as potatoes, melons, oran–ges, tomatoes and peanuts [17]. The most common triggers of PFS in adults are apples (21.1 %), carrots (15.5 %) and peaches (15.5 %) [20]. In our present investigation we have compared the rates of sensitization to cross-reactive proteins PR-10 (containing in birch pollen, peanut, soy, apple, celery, carrot and hazelnut) and nsLTP (containing in wormwood, peanut, kiwi, apple, peach, grape, celery, tomato and hazelnut) in patients with only allergic rhinitis and patients with allergic rhinitis and co-sensitization to food allergens. We have revealed that rates of sensitization to PR-10 and nsLTP were significantly higher in patients with both allergic rhinitis and co-sensitization to food allergens comparing to patients with only allergic rhinitis. It should be noticed that these cross-reactive proteins are containing only in several allergen extracts and/or components of the allergen. So, patient may have allergy to birch, but may not have the sensitization to PR-10 protein, because it is included only in Bet v1 component of birch allergen. And this is why some patients may suffer from allergic rhinitis caused by birch and also have its exacerbations after consuming an apple (cross-reactive allergy due to presence of PR-10 in Bet v1 of birch and Mal d1 of apple), but other patients with birch allergy may eat apples without any consequences. So, such cross-reactive proteins may play role as a one of the causes of allergic rhinitis exacerbations and trigger symptoms after consuming some foods in patients with co-sensitization to several food allergens.

Conclusions

In Kyiv adult population with allergic rhinitis approximately three quarters of patients have co-sensitization to at least one food allergen. Occurrence of GI symptoms was higher in patients with co-sensitization to food allergens. The –higher rates of sensitization to cross-reactive proteins (presented in both inhalant and food allergens) were in patients with allergic rhinitis and food co-sensitization. So, presence of additional sensitization to several food allergens may be the reason of development of not only the GI manifestations, but also of symptoms and features of allergic rhinitis after consuming vegetables, fruits and nuts due to cross-reactivity with inhalant allergens, that should be considered by the physicians when manage and treat the patients with allergic rhinitis.
 
Received 04.10.2023
Revised 16.10.2023
Accepted 25.10.2023

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