Oct 11, 2023
Food allergy is defined as "unexpected effects that occur in the body after oral ingestion of food or food additives, triggered by immunological mechanisms, in which two different reactions occur, namely "IgE-mediated" and "non-IgE-mediated". These unexpected effects are classified as toxic and non-toxic reactions. The amount taken is important because the substance that causes toxic reactions can be seen in anyone when consumed in sufficient amounts. In non-toxic reactions, there is personal sensitivity (Karakılıç, M. et al., 2014).
What is the IL-10 Gene?
IL-10 is a pleiotropic immunoregulatory cytokine produced by T regulatory cells, B cells, monocytes, alveolar macrophages, mast cells, and pulmonary dendritic cells. Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays an important role in the development of allergy. In humans, the IL-10 gene is located on chromosome 1q31-32, a genomic region linked to asthma and related phenotypes (Hunninghake, G. M. et al., 2008).
What is the IL-13 Gene?
IL-13 is produced by various immune cell populations, including primarily Th2 cells but also mast cells, B cells, NK cells, innate lymphoid cells, and granulocytes. IL-13 promotes allergen-induced airway hyperreactivity, epithelial cell damage, goblet cell hyperplasia with mucus hyperproduction, and eosinophilia. IL-13 has an important role in allergic inflammation because it triggers airway hypersensitivity and increases inflammation (Vladich, F. D. et al., 2005).
What is the IL-4 Gene?
IL-4 is produced by T cells, basophils, and mast cells, where it induces the differentiation of T cells into the Th2 subtype. IL-4 is considered a master Th2 switch that also directs the production of other pro-allergic cytokines such as IL-5 and IL-13 by Th2 cells in allergic diseases. IL-4 promotes the development of myeloid dendritic cells and plays a role in the migration of Th2 cells and eosinophils to the inflammatory site. Both IL-4 and IL-13 activate B cells to synthesize IgE, induce goblet cell hyperplasia, trigger airway hyperresponsiveness and mucus hypersecretion (Nur Husna, S. M. et al., 2022).
What is the FLG Gene?
Among the variants studied in atopic diseases, loss-of-function null mutations in the FLG gene are the most commonly transcribed and are the major genetic risk factors for atopic dermatitis and also increase the risk of asthma and peanut allergy. Filaggrin plays a vital role in maintaining hydration levels in the epidermis and preventing the entry of potentially harmful chemical and biological antigens that can trigger immune responses (Saleh, N. M. et al., 2011).
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FOOD ALLERGY |
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|
Genes |
rs |
Minor Allele |
Minor Allele Description |
Reference |
|
IL-10 |
rs1800896 |
A |
High relative risk for food allergy. |
|
|
IL-13 |
rs20541 |
T |
High relative risk for shrimp allergy. |
|
|
IL-4 |
rs2243250 |
T |
High relative risk for food allergy. |
|
|
FLG |
rs61816761 |
A |
Increased relative risk for atopic dermatitis. |
|
The table above includes genes and their polymorphisms that play a role in food allergy. It has been shown that the -1082G→A (rs1800896) cytokine gene polymorphism of IL-10 may provide sensitivity to allergic patients as it can affect the expression of the protein (Gaddam SL. et al., 2012).
Strong associations between IL13 polymorphisms and allergic phenotypes have been identified. IL13 +2044G→A is strongly associated with increased total serum IgE, asthma, atopy, an atopic dermatitis phenotype (Vladich, F. D. et al., 2005).
Depending on the immunological status, IL-4 -589 C/T variation may contribute to susceptibility to various autoimmune diseases by altering IL4 expression levels and thereby modulating anti-inflammatory downregulation (Akkad, D. A. et al., 2007).
REFERENCES
Akkad, D. A., Arning, L., Ibrahim, S. M., & Epplen, J. T. (2007). Sex specifically associated promoter polymorphism in multiple sclerosis affects interleukin 4 expression levels. Genes & Immunity, 8(8), 703-706. https://doi.org/10.1038/sj.gene.6364429
Gaddam SL, Priya VH, Babu BM, Joshi L, Venkatasubramanian S, Valluri V. Association of interleukin-10 gene promoter polymorphism in allergic patients. Genet Test Mol Biomarkers. 2012 Jun;16(6):632-5. doi: 10.1089/gtmb.2011.0255. PMID: 22715992.
Hunninghake, G. M., Soto-Quiros, M. E., Lasky-Su, J., Avila, L., Ly, N. P., Liang, C., Klanderman, B. J., Raby, B. A., Gold, D. R., Weiss, S. T., & Celedon, J. C. (2008). Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations. The Journal of Allergy and Clinical Immunology, 122(1), 93. https://doi.org/10.1016/j.jaci.2008.03.015
Karakılıç, M., Senem, S. U. N. A., Tamer, C. E., & Çopur, Ö. U. (2014). Gıda alerjisi reaksiyonları. Uludağ Üniversitesi Ziraat Fakültesi Dergisi, 28(1), 73-82.
Nur Husna, S. M., Shukri, N. M., Mohd Ashari, N. S., & Wong, K. K. (2022). IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ, 10. https://doi.org/10.7717/peerj.13444
Saleh, N. M., Raj, S. M., Smyth, D. J., Wallace, C., M. Howson, J. M., Bell, L., Walker, N. M., Stevens, H. E., & Todd, J. A. (2011). Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes. Diabetes/Metabolism Research and Reviews, 27(8), 838-843. https://doi.org/10.1002/dmrr.1259
Vladich, F. D., Brazille, S. M., Stern, D., Peck, M. L., Ghittoni, R., & Vercelli, D. (2005). IL-13 R130Q, a common variant associated with allergy and asthma, enhances effector mechanisms essential for human allergic inflammation. Journal of Clinical Investigation, 115(3), 747-754. https://doi.org/10.1172/JCI22818