Abstract
By analyzing 14 food allergen-specific IgG antibodies in 1299 children residing in Henan province of China, we aimed to gain a preliminary understanding of food intolerance in children living in this region. Specific IgG antibodies for 14 food allergens were semi-quantitatively detected in the sera of subjects using enzyme-linked immunosorbent assays. The total positive rate for food allergen IgG antibodies was 99.9%. Of the 14 food allergens tested, sera most frequently tested positive for specific IgG antibodies for the following five food allergens, listed from the highest positive rate to the lowest: egg, milk, soybean, cod, and crab. The total positive rate for each food allergen-specific IgG antibody showed no statistically significant gender-based differences (p > 0.05), nor did the total positive rate for IgG antibodies for all the types of food allergens (p > 0.05). The positive rates of allergen-specific IgG antibodies for milk, beef, chicken, pork, mushrooms, and eggs (p < 0.05) showed a statistically significant difference between the 0- to 3-year-old and 4- to 11-year-old groups. Food intolerance is prevalent in children.
INTRODUCTION
Food allergy refers to an abnormal reaction that some individuals experience after they eat foods that are typically harmless to the human body. Its pathogenesis involves an immune-mediated reaction induced by antigen substances contained in food. In recent allergy studies, researchers have primarily focused on type I allergic reactions mediated by IgE, whereas research pertaining to IgG is limited. IgE and IgG function in the reactions of the immediate- and late-phase responses, respectively. While IgE is the main antibody involved in type I allergic reactions, IgG is associated with type III allergic reactions, which are referred to as food intolerances. A correlative statistical analysis of patients (Erlangen University Hospital, Germany) with food allergy symptoms showed that 15–20% experienced non-IgE-mediated immune responses (i.e., food intolerances).[Citation1] Food intolerance is becoming more common and has become the focus of research worldwide.[Citation2] Food intolerance is a complex allergic disease in which the immune system of the human body treats one or various types of food as harmful substances, resulting in an excessive protective immune response and the production of food-specific IgG antibodies. Food-specific IgG antibodies combine with food particles to form immune complexes that cause inflammation in tissues, which manifest as symptoms and systemic diseases.[Citation3] Food intolerance is typically caused by a variety of foods rather than by a single food and can cause multi-system discomfort,[Citation4] including gastrointestinal irritation, eczema, dermatitis, and migraines.[Citation5–Citation9] Allergic reactions caused by food mainly occur in the skin and mucosa. Respiratory and gastrointestinal symptoms, and allergic skin diseases such as eczema, urticaria, allergic purpura, and atopic dermatitis are related to food allergies.[Citation10] Food intolerance can occur in individuals of all ages, but infants and children may have a higher incidence than adults. A series of symptoms caused by food intolerance generally appear in a few hours to several days after the allergen is consumed. If the offending food is consumed for a long period, these symptoms can be aggravated or become chronic. Because the symptoms lack specificity, patient self-diagnosis is difficult. Statistics show that up to 45% of people has some degree of intolerance to certain foods.[Citation11] Clinical symptoms of food intolerance vary in different individuals; thus, an accurate and timely diagnosis is very important to treat the reaction. A diagnosis can be made using several means and may involve taking a detailed history and performing related laboratory tests.[Citation12–Citation14] Food intolerance is produced by the over-protective immune response of the human immune system toward one or various foods that enter the human body, generating food-specific IgG antibodies. Therefore, detection of specific IgG antibodies could determine whether the symptoms or diseases are due to food intolerance. A method for the in vitro detection of specific IgG antibodies in serum is applicable to various individuals, including children. Fourteen food allergen-specific IgG antibodies were analyzed in 1299 children living in Henan province. We aimed to garner a preliminary understanding of food intolerance in children living in this region.
MATERIALS AND METHODS
Subjects
The test subjects were 1299 children (0–11 years of age) with food allergen-specific IgG antibodies who were patients in Children’s Hospital of Zhengzhou City between January and May 2012. Of the 1299 patients, 846 were 0–3 years of age, while 453 were 4–11 years of age. Of these, 854 patients were boys and 445 were girls. This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Children’s Hospital of Zhengzhou City. Written informed consent was obtained from all participants.
Enzyme-Linked Immunosorbent Assay (ELISA)
An ELISA kit for the detection of food allergen-specific IgG antibodies (Biomerica Inc, USA) was used for semi-quantitative detection of 14 food allergen-specific IgG antibodies in the serum of the study subjects. The assay was performed in strict accordance with the kit instructions. Results were scored as follows: IgG < 50 U/mL, grade 0 (negative; i.e., food tolerance); IgG 50–100 U/mL, grade +1 (mildly sensitive; i.e., mild intolerance), IgG 100–200 U/mL, grade +2 (moderately sensitive; i.e., moderate intolerance), IgG > 200 U/mL, grade +3 (severe sensitivity; i.e., severe intolerance).
Statistical Analysis
The results were statistically analyzed using the SPSS 17.0 software. To compare the rates, Chi-squared tests were performed. p < 0.05 was considered statistically significant.
RESULTS
Rates of Positive Detection
The total positive rate for the 14 tested food allergen IgG antibodies was 99.9% (1298). The positive rates of the food allergen-specific IgG antibodies, listed from highest to lowest rate, were as follows: egg (84.1%, 1092), milk (79.8%, 1036), cod (48.7%, 633), soybean (28.3%, 367), crab (22.6%, 294), tomato (19%, 247), beef (15.5%, 201), rice (14.5%, 189), wheat (13.5%, 176), chicken (9.9%, 129), corn (8%, 104), shrimp (7.7%, 100), pork (4.8%, 63), and mushroom (3.7%, 48).
Grading of IgG Antibodies
Grading of the 14 food allergen-specific IgG antibodies is shown in . Statistically significant differences existed between the 4 grades of the 14 food allergen IgG antibodies (p < 0.05). IgG antibody levels were graded between +1 and +3. Milk and egg allergen-specific IgG antibodies generally received a grade of +2, while the other 12 food allergen-specific IgG antibodies were mainly scored with a grade of +1.
TABLE 1 Grading analysis of 14 kinds of food allergen specific IgG antibody [n, (%)]
Intergroup Analysis of Gender
In the serum samples, the positive rate for IgG antibodies for food allergens was 99.9% (853) for boys and 100% for girls (445; ). The total positive rate had no statistically significant gender-based difference (p > 0.05). The positive rates for each of the 14 food allergen-specific IgG antibodies also did not differ significantly with respect to gender (p > 0.05).
TABLE 2 Analysis of positive rate of food allergen specific IgG antibody in different gender [n, (%)]
Intergroup Analysis of Age
The positive rates for IgG antibodies in the two age groups are shown in . The positive rates for allergen IgG antibodies to beef, milk, chicken, pork, and mushroom were higher in children 0–3 years of age than in those who were 4–11 years of age. Conversely, the positive rate for allergen-specific IgG antibodies to egg was lower in 0- to 3-year-old than in 4- to 11-year-old children. These differences were statistically significant (p < 0.05). The differences in the positive rates for allergen-specific IgG antibodies to cod, rice, corn, shrimp, crab, tomato, soybean, and wheat were not statistically significant between children of the two age groups (p > 0.05).
TABLE 3 Analysis of positive rate of food IgG antibody between different age groups [n, (%)]
DISCUSSION
Because food intolerance is a new field of study in terms of allergic diseases, its mechanism has not been fully elucidated, but its existence and consequences are generally recognized.[Citation15,Citation16] For complete absorption, food in the digestive tract should be decomposed into amino acids, glycerol, or monosaccharides; however, according to the widely recognized mechanism of food intolerance, the lack of required enzymes causes food to enter the intestine as peptides or other molecular forms that are identified as foreign substances by the body, leading to the production of food-specific IgG antibodies. IgG antibodies and food particles can form immune complexes that cause inflammation in all tissues, including the vascular system, thus leading to development of symptoms and systemic diseases.
In this study, we used an ELISA for semi-quantitative detection of 14 food allergen-specific IgG antibodies in the sera of subjects. Food intolerance was observed in 99.9% of the children examined. This elevated positive rate might be attributed to the fact that all the investigated subjects were children in our hospital with clinical symptoms suspected to be related to food intolerance. The patients that were deemed food tolerant may have experienced diseases not related to food intolerance or their food intolerance was not attributed to the 14 foods tested. In order from the highest to the lowest, the positive rates for the 14 food allergen-specific IgG antibodies were as follows: egg, milk, soybean, cod, crab, tomato, beef, rice, wheat, corn, chicken, shrimp, pork, and mushrooms. This order may be related to the fact that eggs, milk, and cod are animal-derived high-protein foods, and soybean is a plant-derived high-protein food. Glycoproteins with an acidic isoelectric point can usually tolerate food processing, heating, and cooking, but they also resist the intestinal digestive functions. Digestive system function in children is not perfect; thus, they are susceptible to forming IgG antibodies to foreign proteins in their intestinal tracts. Although chicken, shrimp, and pork are animal-derived high-protein foods, the positive rates for IgG antibodies were low. The former may be because it can induce an immediate IgE-mediated hypersensitivity reaction, whereas we focused on the delayed type of hypersensitivity mediated by IgG. The latter may be related to their different protein compositions. Grading of these food allergen-specific IgG antibodies showed that only specific IgG antibodies to milk and eggs received grades of +2, suggesting that subjects showed moderate intolerance to these foods. These data were in partial accordance with that of other reports. The food intolerances in our subjects showed no statistically significant gender differences. These data differed from those reported by Zhuo et al.[Citation17] for a study in Hangzhou city that showed the incidence of food intolerance in boys is generally higher than that in girls. These differences may be attributed to population, geographical, or dietary differences. Detection of food allergen-specific IgG antibodies can help in the preliminarily determination of the presence of food intolerance symptoms, thus providing a novel method for diagnosis. For food-intolerant children, a targeted meal plan should be made by using methods such as food restriction or fasting, alternating foods, and changing cooking habits to avoid the offending food that inflicts damage to the body and to control the continuous development of the disease.[Citation18–Citation21] According some research, food manufacturers need more careful management of allergenic food ingredients and our parents must stay on the alert, questioning the place where they are going to have their meals in terms of the ingredients used, verifying whether the food is really free of allergens, thus reducing the health hazard.[Citation22–Citation25] More research should focus on food allergens. Schulzit found that activation of the aryl hydrocarbon receptor by dioxin-like compounds suppresses allergic sensitizations.[Citation26,Citation27] Vera Medeiros found a new way using bromelain as a proteolytic enzyme for the production of a partially hydrolyzed bovine milk formula, without changing the milk’s organoleptic and nutritional properties to get better digestibility. Detection of food intolerance provides a new direction for disease diagnosis and prevention, and a new avenue for clinical treatment.
Related Research Data
REFERENCES
- Zopf, Y.; Baenkler, H.W.; Silbermann, A.; Hahn, E.G.; Raithel, M. The differential diagnosis of food intolerance. Deutsches Ärzteblatt International 2009, 106 (21), 359–369.
- Ho, M.H.; Wong, W.H.; Chang, C. Clinical spectrum of food allergies: A comprehensive review. Clinical Reviews in Allergy & Immunology 2014, 46 (3), 225–240.
- Pirer, M.A.; Hoskmg, C.S.; Hill, D.J. Cow’s milk allergy and eczema: Patterns of the antibody response to cow’s milk in allergic skin disease. Clinical Allergy 1982, 12 (4), 385–390.
- Patel, N.J.; Jenzarli, A. Does food intolerance play a role in recurrent respiratory papillomatosis? International Forum of Allergy & Rhinology 2012, 2 (1), 85–88.
- Morfin-Maciel, B.; Medina, A.; Espinosa Rosales, F.; Berrón, R.; Huerta López, J. Central net-VOUS system involvement in a child with polyartefitis nodosa and severe atopic dermatitis. Revista Alergia Mexico 2002, 49 (6), 189–195.
- Ogden, J.; Leftwich, J.; Nelson, M. The development and evaluation of a nurse led food intolerance clinic in primary care. Patient Education and Counseling 2011, 85 (2), e1–5.
- Sheab-Min, Y.; Choon-Kook, S. The relevance of specific serum IgG, IsG4, and IgE in the determination of shrimp and crab allergies in Malaysian allergic rhinitis patients. Asian Pacific Journal of Cancer Prevention 2001, 19 (1), 7–10.
- Zar, S.; Kurnar, D. Role of food hypersensitivity in irritable bowel syndrome. Minerva Medica 2002, 93 (5), 403–412.
- Zigich, S.; Heuberger, R. The relationship of food intolerance and irritable bowel syndrome in adults. Gastroenterology Nursing 2013, 36 (4), 275–282.
- Potel, T.; Gawkrodger, D.J. Food allergy in patients with eczema: Immediate symptoms are usual, with nuts and tomatoes the major allergens. Journal of the European Academy of Dermatology and Venereology 2011, 25 (7), 865–867.
- Saeed, S.A.; Ali, R.; Ali, S.S.; Ahmad, N.; Basit, A.; Urfy, M.Z. A closer look at food allergy and intolerance. JCPSP-journal of the College of Physicians and Surgeons Pakistan 2004, 14 (6), 376–380.
- Baldacci, S.; Omenaas, E.; Oryszezyn, M.P. Allergy markers in respiratory epidemiology. European Respiratory Journal 2001, 17 (4), 773–790.
- Lavine, E. Blood testing for sensitivity, allergy, or intolerance to food. Canadian Medical Association Journal 2012, 184 (6), 666–668.
- Palmieri, B.; Esposito, A.; Capone, S.; Fistetto, G.; Iannitti, T. Food intolerance: Reliability and characteristics of different diagnostic alternative tests. Minerva Gastroenterologicae Dietologica 2011, 57 ( 1 Suppl 1), 1–10.
- Liew, W.K.; Williamson, E.; Tang, M.L. Anaphylaxis fatalities and admissions in Australia. Journal of Allergy and Clinical Immunology 2009, 123 (2), 434–442.
- Poulos, L.M.; Waters, A.M.; Correll, P.K.; Loblay, R.H.; Marks, G.B. Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993–1994 to 2004–2005. Journal of Allergy and Clinical Immunology 2007, 120 (4), 878–884.
- Zhuo, G.; Wang, H.; Zheng, H. Food hypersensitivity in Hangzhou children. Chinese Journal of Health Laboratory Technology 2009, 19 (10), 2402–2404.
- Anderson, J. Food-chemical intolerance in the breastfed infant. Breastfeed Review 2013, 21 (1), 17–20.
- Garzon, D.L.; Kempker, T.; Piel, P. Primary care management of food allergy and food intolerance. The Nurse Practitioner: The American Journal of Primary Health Care 2011, 36 (12), 34–40.
- Gupta, R.S.; Dyer, A.A.; Jain, N.; Greenhawt, M.J. Childhood food allergies: Current diagnosis, treatment, and management strategies. Mayo Clinic Proceedings 2013, 88 (5), 512–526.
- Host, A.; Halkell, S.; Muraro, A.; et al. Dietary prevention of allergic diseases in infants and small children. Pediatric Allergy and Immunology 2008, 19 (1), 1–4.
- Waisarayutt, C.; Surojanametakul, V.; Kaewpradub, S.; Shoji, M.; Ito, T.; Tamura, H. Investigation on the understanding and implementation of food allergen management among Thai food manufacturers. Food Control 2014, 46,182–188.
- Marambe, H.K.; Mclntosh, T.C.; Cheng, B.; Wanasundara, J.P.D. Quantification of major 2S allergen protein of yellow mustard using anti-Sin a 1 epitope antibody. Food Control 2014, 44, 233–241.
- Ajala, A.R.; Cruz, A.G.; Faria, J.A.F.; Walter, E.H.M.; Granato, D.; Ana, A.S.S. Food allergens: Knowledge and practices of food handlers in restaurants. Food Control 2010, 21 (10), 1318–1321.
- Surojanametakul, V.; Khaiprapai, P.; Jithan, P.; et al. Investigation of undeclared food allergens in commercial Thai food products. Food Control 2012, 23 (1), 1–6.
- Schulz, V.J.; Smit, J.J.; Pieters, R.H.H. The aryl hydrocarbon receptor and food allergy. Veterinary Quarterly 2013, 33 (2), 94–107.
- Medeiros, V.; Rainha, N.; Paiva, L.; Lima, E.; Baptista, J. Bovine milk formula based on partial hydrolysis of caseins by bromelain enzyme: Better digestibility and angiotensin-converting enzyme-inhibitory properties. International Journal of Food Properties 2014, 17 (4), 806.