Abstract
Allergic reactions to foods are an important medical problem throughout the industrialized world. The occurrence of food allergy appears to be strongly in.uenced by genetics, but the basis of the genetic predisposition to food allergy has not been differentiated from that for atopy in general. In addition, genetic susceptibility alone does not explain the prevalence of food allergy satisfactorily, leaving ample room to consider the importance of environmental in.uences (external, maternal, and gastrointestinal environment) and interactions between the host and the environment. Several features of food allergy are highlighted in this review: 1) patients with severe food allergies are overwhelmingly atopic, but food allergy occurs only in approximately 10% of patients with other atopic diseases; 2) most patients are clinically reactive to a single food, and although a substantial minority have multiple food allergies, the variety of bonefide food allergies in a given individual is limited; 3) foods contain multiple proteins whereas only a small subset are allergenic; 4) there is likely an important contribution of the environment, becoming manifest in genetically susceptible individuals.
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References and Recommended Reading
Sampson HA: Update on food allergy. J Allergy Clin Immunol 2004, 113:805–819; quiz 820. An excellent update.
Sampson HA: Food allergy. JAMA 1997, 278:1888–1894.
Hourihane JB, Kilburn SA, Nordlee JA, et al.: An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: a randomized, doubleblind, placebo-controlled food challenge study. J Allergy Clin Immunol 1997, 100:596–600.
Kagan RS, Joseph L, Dufresne C, et al.: Prevalence of peanut allergy in primary-school children in Montreal, Canada. J Allergy Clin Immunol 2003, 112:1223–1228.
Lack G: New developments in food allergy: old questions remain. J Allergy Clin Immunol 2004, 114:127–130. Highlights the important clinical questions regarding food allergy.
Burks W, Bannon GA, Sicherer S, Sampson HA: Peanutinduced anaphylactic reactions. Int Arch Allergy Immunol 1999, 119:165–172.
Bock SA, Munoz-Furlong A, Sampson HA: Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 2001, 107:191–193.
Sicherer SH, Furlong TJ, Munoz-Furlong A, et al.: A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants. J Allergy Clin Immunol 2001, 108:128–132.
Tariq SM, Stevens M, Matthews S, et al.: Cohort study of peanut and tree nut sensitisation by age of 4 years. BMJ 1996, 313:514–517.
Grundy J, Matthews S, Bateman B, et al.: Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol 2002, 110:784–789.
Sicherer SH, Munoz-Furlong A, Sampson HA: Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol 2004, 114:159–165.
Hourihane JO, Kilburn SA, Dean P, Warner JO: Clinical characteristics of peanut allergy. Clin Exp Allergy 1997, 27:634–639.
Sicherer SH: Clinical update on peanut allergy. Ann Allergy Asthma Immunol 2002, 88:350–361; quiz 361–352, 394.
Hourihane JO: Recent advances in peanut allergy. Curr Opin Allergy Clin Immunol 2002, 2:227–231.
Lack G, Fox D, Northstone K, Golding J: Factors associated with the development of peanut allergy in childhood. N Engl J Med 2003, 348:977–985.
Vadas P, Wai Y, Burks W, Perelman B: Detection of peanut allergens in breast milk of lactating women. JAMA 2001, 285:1746–1748.
Warner JO: Peanut allergy: a major public health issue. Pediatr Allergy Immunol 1999, 10:14–20.
Sampson HA: Food allergy: when mucosal immunity goes wrong. J Allergy Clin Immunol 2005, 115:139–141. Excellent discussion of mucosal immunity and food allergy
Bjorksten B: Genetic and environmental risk factors for the development of food allergy. Curr Opin Allergy Clin Immunol 2005, 5:249–253. Thorough review of maternal and gastrointestinal factors and the development of food allergy.
Larsen JN, Lowenstein H: Allergen nomenclature. J Allergy Clin Immunol 1996, 97:577–578.
Chapman MD: Allergen nomenclature. In Allergens and Allergen Immunotherapy. Edited by Lockey RF, Bukantz SC, Bousquet J. Florence, KY: Marcel Dekker; 2004:51–64.
Breiteneder H, Radauer C: A classi.cation of plant food allergens. J Allergy Clin Immunol 2004, 113:821–830; quiz 831. Worthwhile review of the categories of food proteins that are allergenic
Bannon GA: What makes a food protein an allergen? Curr Allergy Asthma Rep 2004, 4:43–46. A thoughtful consideration of how food allergens are different from other food proteins.
Breiteneder H, Mills EN: Molecular properties of food allergens. J Allergy Clin Immunol 2005, 115:14–23; quiz 24. A companion to Breiteneder and Radauer [22].
Jenkins JA, Grif.ths-Jones S, Shewry PR, et al.: Structural relatedness of plant food allergens with speci.c reference to cross-reactive allergens: an in silico analysis. J Allergy Clin Immunol 2005, 115:163–170. A novel approach that may allow a better understanding of allergenic food proteins.
Bredehorst R, David K: What establishes a protein as an allergen? J Chromatogr B Biomed Sci Appl 2001, 756:33–40.
Shearer W, Fleischer T: The immune system. In Middleton’s Allergy: Principles & Practice, vol 1. Edited by Addinson N Jr, Yunginger J, Busse W, et al. St. Louis, MO: Mosby; 2003:1–14.
Acton R: The major histocompatibility complex. In Clinical Immunology: Principles and Practice, vol 1. Edited by Rich R, Fleisher T, Shearer W, et al. St. Louis, MO: Mosby; 2001:6.1–6.13.
Kapsenberg ML, Jansen HM: Antigen presentation and immunoregulation. In Middleton’s Allergy: Principles & Practice, vol 2. Edited by Addinson N Jr, Yunginger J, Busse W, et al. St. Louis, MO: Mosby; 2003:177–188.
Robinson JH, Delvig AA: Diversity in MHC class II antigen presentation. Immunology 2002, 105:252–262.
Gregersen PK, Silver J, Winchester RJ: The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987, 30:1205–1213.
Ou D, Mitchell LA, Tingle AJ: A new categorization of HLA DR alleles on a functional basis. Hum Immunol 1998, 59:665–676. This review discusses how disparate HLA alleles may have similar function.
Torres-Galvan MJ, Quiralte J, Blanco C, et al.: Pocket 4 in the HLA-DRB1 antigen-binding groove: an association with atopy. Allergy 2000, 55:398–401.
Blanco C, Sanchez-Garcia F, Torres-Galvan MJ, et al.: Genetic basis of the latex-fruit syndrome: association with HLA class II alleles in a Spanish population. J Allergy Clin Immunol 2004, 114:1070–1076. Successful application of the concepts discussed by Ou et al. [32] to the problem of food allergy.
Fontenot AP, Torres M, Marshall WH, et al.: Beryllium presentation to CD4+ T cells underlies disease-susceptibility HLA-DP alleles in chronic beryllium disease. Proc Natl Acad Sci U S A 2000, 97:12717–12722.
McCanlies EC, Kreiss K, Andrew M, Weston A: HLA-DPB1 and chronic beryllium disease: a HuGE review. Am J Epidemiol 2003, 157:388–398.
Klareskog L, Alfredsson L, Rantapaa-Dahlqvist S, et al.: What precedes development of rheumatoid arthritis? Ann Rheum Dis 2004, 63(Suppl 2):ii28-ii31.
Wang Z, Farris GM, Newman LS, et al.: Beryllium sensitivity is linked to HLA-DP genotype. Toxicology 2001, 165:27–38.
Halapi E, Hakonarson H: Recent development in genomic and proteomic research for asthma. Curr Opin Pulm Med 2004, 10:22–30.
Hopp RJ, Bewtra AK, Watt GD, et al.: Genetic analysis of allergic disease in twins. J Allergy Clin Immunol 1984, 73:265–270.
Lichtenstein P, Svartengren M: Genes, environments, and sex: factors of importance in atopic diseases in 7–9-yearold Swedish twins. Allergy 1997, 52:1079–1086.
Sicherer SH, Furlong TJ, Maes HH, et al.: Genetics of peanut allergy: a twin study. J Allergy Clin Immunol 2000, 106:53–56. Evidence that there is a strong genetic factor driving the phenotype of peanut allergy.
Liu AH: Endotoxin exposure in allergy and asthma: reconciling a paradox. J Allergy Clin Immunol 2002, 109:379–392.
Liu AH, Murphy JR: Hygiene hypothesis: fact orfiction? J Allergy Clin Immunol 2003, 111:471–478.
Eder W, von Mutius E: Hygiene hypothesis and endotoxin: What is the evidence? Curr Opin Allergy Clin Immunol 2004, 4:113–117.
Liu AH: Something old, something new: indoor endotoxin, allergens and asthma. Paediatr Respir Rev 2004, 5(Suppl A):S65-S71.
Holla AD, Roy SR, Liu AH: Endotoxin, atopy and asthma. Curr Opin Allergy Clin Immunol 2002, 2:141–145.
Roy SR, Schiltz AM, Marotta A, et al.: Bacterial DNA in house and farm barn dust. J Allergy Clin Immunol 2003, 112:571–578.
Bottcher MF, Nordin EK, Sandin A, et al.: Micro.oraassociated characteristics in faeces from allergic and nonallergic infants. Clin Exp Allergy 2000, 30:1590–1596.
Kalliomaki M, Salminen S, Poussa T, et al.: Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003, 361:1869–1871.
Gern JE, Reardon CL, Hoffjan S, et al.: Effects of dog ownership and genotype on immune development and atopy in infancy. J Allergy Clin Immunol 2004, 113:307–314.
Woo JG, Assa’ad A, Heizer AB, et al.: The -159 C-->T polymorphism of CD14 is associated with nonatopic asthma and food allergy. J Allergy Clin Immunol 2003, 112:438–444. The first hint that host response to endotoxin may be an important risk factor for the development of food allergy.
Bashir ME, Louie S, Shi HN, Nagler-Anderson C: Toll-like receptor 4 signaling by intestinal microbes in.uences susceptibility to food allergy. J Immunol 2004, 172:6978–6987. An excellent murine study reinforcing the importance of commensal organisms and the host response to bacterial products in susceptibility to food allergy.
Zambelli-Weiner A, Ehrlich E, Stockton ML, et al.: Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study. J Allergy Clin Immunol 2005, 115:1203–1209.
Arbour NC, Lorenz E, Schutte BC, et al.: TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000, 25:187–191.
Yang IA, Barton SJ, Rorke S, et al.: Toll-like receptor 4 polymorphism and severity of atopy in asthmatics. Genes Immun 2004, 5:41–45.
Fageras Bottcher M, Hmani-Aifa M, Lindstrom A, et al.: A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children. J Allergy Clin Immunol 2004, 114:561–567.
Raby BA, Klimecki WT, Laprise C, et al.: Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes. Am J Respir Crit Care Med 2002, 166:1449–1456.
Hourihane JO, Dean TP, Warner JO: Peanut allergy in relation to heredity, maternal diet, and other atopic diseases: results of a questionnaire survey, skin prick testing, and food challenges. BMJ 1996, 313:518–521.
Donovan GR, Manolios N, Weiner JM, et al.: A family study of allergy: segregation with HLA but not with T-cell receptor genes. J Allergy Clin Immunol 1996, 97:712–713.
Howell WM, Turner SJ, Hourihane JO, et al.: HLA class II DRB1, DQB1 and DPB1 genotypic associations with peanut allergy: evidence from a family-based and casecontrol study. Clin Exp Allergy 1998, 28:156–162. Important because this is the first report to look at HLA alleles and food allergy in a fairly large population. However, the data do not support an association.
Hand S, Darke C, Thompson J, et al.: Human leucocyte antigen polymorphisms in nut-allergic patients in South Wales. Clin Exp Allergy 2004, 34:720–724.
Rihs HP, Chen Z, Rueff F, et al.: HLA-DQ8 and the HLADQ8-DR4 haplotype are positively associated with the hevein-speci.c IgE immune response in health care workers with latex allergy. J Allergy Clin Immunol 2002, 110:507–514.
Mayer L: Mucosal immunity. Pediatrics 2003, 111:1595–1600.
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al.: Recognition of commensal micro.ora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118:229–241. A landmark murine study clearly demonstrating the power of microbial commensals and the host response to them.
LeVan TD, Bloom JW, Bailey TJ, et al.: A common single nucleotide polymorphism in the CD14 promoter decreases the af.nity of Sp protein binding and enhances transcriptional activity. J Immunol 2001, 167:5838–5844.
Baldini M, Lohman IC, Halonen M, et al.: A Polymorphism* in the 5′ fianking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol 1999, 20:976–983.
Koppelman GH, Reijmerink NE, Colin Stine O, et al.: Association of a promoter polymorphism of the CD14 gene and atopy. Am J Respir Crit Care Med 2001, 163:965–969.
Leung TF, Tang NL, Sung YM, et al.: The C-159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children. Pediatr Allergy Immunol 2003, 14:255–260.
Kabesch M, Hasemann K, Schickinger V, et al.: A promoter polymorphism in the CD14 gene is associated with elevated levels of soluble CD14 but not with IgE or atopic diseases. Allergy 2004, 59:520–525.
Sengler C, Haider A, Sommerfeld C, et al.: Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort. Clin Exp Allergy 2003, 33:166–169.
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Dreskin, S.C. Genetics of food allergy. Curr Allergy Asthma Rep 6, 58–64 (2006). https://doi.org/10.1007/s11882-006-0012-9
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DOI: https://doi.org/10.1007/s11882-006-0012-9