The relationship between IgE and allergic disease
- Jeff Stokes, MD, FAAAAI, FACAAI
Jeff Stokes, MD, FAAAAI, FACAAI
- Professor of Pediatrics
- Washington University in St. Louis School of Medicine
- Thomas B Casale, MD
Thomas B Casale, MD
- Executive Vice President, American Academy of Allergy Asthma and Immunology
- Professor of Medicine
- University of South Florida
Allergen-specific immunoglobulin E (IgE) is integral to the pathogenesis of allergic disorders. However, the utility of measuring total serum IgE or allergen-specific IgE for purposes of diagnosis and management is variable. It is important to recognize that levels of total IgE rarely provide information about IgE to specific allergens, and the presence of IgE to a specific allergen does not necessarily equate to a clinically meaningful allergic response to that substance. It is also necessary to demonstrate that the individual develops appropriate signs and symptoms upon exposure to the allergen in question.
This topic will review basic concepts concerning the generation of the allergic response and provide an overview of the roles of total and allergen-specific IgE in various allergic diseases. The biology of IgE and the diagnosis of specific allergic diseases are discussed separately. (See "The biology of IgE" and "Diagnosis of asthma in adolescents and adults" and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis" and "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)".)
The terms "atopy," "sensitization," and "allergy" are often used loosely in the medical literature, although each has a distinct definition.
Atopy — Atopy is the genetic predilection to produce specific IgE following exposure to allergens. At a cellular level, atopy appears to result, in part, from a predisposition toward a certain response on the part of CD4+ T helper cells called a T helper type 2 (Th2) response . The CD4 molecule is a coreceptor in the T cell receptor complex and also binds proteins of the major histocompatibility complex (MHC). Th2 cells secrete large quantities of interleukin-4 (IL-4) and interleukin-13 (IL-13), which promote the production of allergen-specific IgE by plasma cells. (See "T helper subsets: Differentiation and role in disease" and "The biology of IgE", section on 'Regulation of synthesis'.)
Sensitization — Sensitization refers to the production of allergen-specific IgE. Sensitization to an allergen is not synonymous with being allergic to that allergen, because individuals may produce IgE to allergens in a given substance, but not develop symptoms upon exposure to that substance. It is unclear why some individuals demonstrate only sensitization while others have active allergic disease.
- Borish L. Allergic rhinitis: systemic inflammation and implications for management. J Allergy Clin Immunol 2003; 112:1021.
- Salo PM, Calatroni A, Gergen PJ, et al. Allergy-related outcomes in relation to serum IgE: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol 2011; 127:1226.
- Nicolaou N, Poorafshar M, Murray C, et al. Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. J Allergy Clin Immunol 2010; 125:191.
- Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res 2011; 3:67.
- Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol 2010; 105:99.
- Ker J, Hartert TV. The atopic march: what's the evidence? Ann Allergy Asthma Immunol 2009; 103:282.
- von Kobyletzki LB, Bornehag CG, Hasselgren M, et al. Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort. BMC Dermatol 2012; 12:11.
- Leung DY, Nicklas RA, Li JT, et al. Disease management of atopic dermatitis: an updated practice parameter. Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol 2004; 93:S1.
- Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2010; 125:S73.
- Klink M, Cline MG, Halonen M, Burrows B. Problems in defining normal limits for serum IgE. J Allergy Clin Immunol 1990; 85:440.
- Omenaas E, Bakke P, Elsayed S, et al. Total and specific serum IgE levels in adults: relationship to sex, age and environmental factors. Clin Exp Allergy 1994; 24:530.
- Wittig HJ, Belloit J, De Fillippi I, Royal G. Age-related serum immunoglobulin E levels in healthy subjects and in patients with allergic disease. J Allergy Clin Immunol 1980; 66:305.
- Marsh DG, Bias WB, Ishizaka K. Genetic control of basal serum immunoglobulin E level and its effect on specific reaginic sensitivity. Proc Natl Acad Sci U S A 1974; 71:3588.
- Bønnelykke K, Pipper CB, Bisgaard H. Transfer of maternal IgE can be a common cause of increased IgE levels in cord blood. J Allergy Clin Immunol 2010; 126:657.
- Kaan A, Dimich-Ward H, Manfreda J, et al. Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months. Ann Allergy Asthma Immunol 2000; 84:37.
- Wen HJ, Wang YJ, Lin YC, et al. Prediction of atopic dermatitis in 2-yr-old children by cord blood IgE, genetic polymorphisms in cytokine genes, and maternal mentality during pregnancy. Pediatr Allergy Immunol 2011; 22:695.
- Ferguson A, Dimich-Ward H, Becker A, et al. Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort. Pediatr Allergy Immunol 2009; 20:710.
- Pesonen M, Kallio MJ, Siimes MA, et al. Cord serum immunoglobulin E as a risk factor for allergic symptoms and sensitization in children and young adults. Pediatr Allergy Immunol 2009; 20:12.
- Shah PS, Wegienka G, Havstad S, et al. The relationship between cord blood immunoglobulin E levels and allergy-related outcomes in young adults. Ann Allergy Asthma Immunol 2011; 106:245.
- Sherrill DL, Stein R, Halonen M, et al. Total serum IgE and its association with asthma symptoms and allergic sensitization among children. J Allergy Clin Immunol 1999; 104:28.
- Hagy GW, Settipane GA. Risk factors for developing asthma and allergic rhinitis. A 7-year follow-up study of college students. J Allergy Clin Immunol 1976; 58:330.
- Settipane RJ, Hagy GW, Settipane GA. Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow-up study of college students. Allergy Proc 1994; 15:21.
- Kartasamita CB, Rosmayudi O, Demedts M. Total serum IgE and eosinophil count in children with and without a history of asthma, wheezing, or atopy in an urban community in Indonesia. The Respiratory Disease Working Group. J Allergy Clin Immunol 1994; 94:981.
- Sunyer J, Antó JM, Castellsagué J, et al. Total serum IgE is associated with asthma independently of specific IgE levels. The Spanish Group of the European Study of Asthma. Eur Respir J 1996; 9:1880.
- Beeh KM, Ksoll M, Buhl R. Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals. Eur Respir J 2000; 16:609.
- Gergen PJ, Arbes SJ Jr, Calatroni A, et al. Total IgE levels and asthma prevalence in the US population: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol 2009; 124:447.
- Rajakulasingam K, Till S, Ying S, et al. Increased expression of high affinity IgE (FcepsilonRI) receptor-alpha chain mRNA and protein-bearing eosinophils in human allergen-induced atopic asthma. Am J Respir Crit Care Med 1998; 158:233.
- Humbert M, Grant JA, Taborda-Barata L, et al. High-affinity IgE receptor (FcepsilonRI)-bearing cells in bronchial biopsies from atopic and nonatopic asthma. Am J Respir Crit Care Med 1996; 153:1931.
- den Otter I, Silva LF, Carvalho AL, et al. High-affinity immunoglobulin E receptor expression is increased in large and small airways in fatal asthma. Clin Exp Allergy 2010; 40:1473.
- Zhou J, Zhou Y, Lin LH, et al. Association of polymorphisms in the promoter region of FCER1A gene with atopic dermatitis, chronic uticaria, asthma, and serum immunoglobulin E levels in a Han Chinese population. Hum Immunol 2012; 73:301.
- Anupama N, Vishnu Sharma M, Nagaraja HS, Ramesh Bhat M. The serum immunoglobulin E level reflects the severity of bronchial asthma. Thai Journal of Physiological Sciences 2005; 18:35.
- Wood RA, Phipatanakul W, Hamilton RG, Eggleston PA. A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy. J Allergy Clin Immunol 1999; 103:773.
- Sunyer J, Antó JM, Sabrià J, et al. Relationship between serum IgE and airway responsiveness in adults with asthma. J Allergy Clin Immunol 1995; 95:699.
- Sears MR, Burrows B, Flannery EM, et al. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991; 325:1067.
- Burrows B, Sears MR, Flannery EM, et al. Relations of bronchial responsiveness to allergy skin test reactivity, lung function, respiratory symptoms, and diagnoses in thirteen-year-old New Zealand children. J Allergy Clin Immunol 1995; 95:548.
- Sherrill DL, Halonen M, Burrows B. Relationships between total serum IgE, atopy, and smoking: a twenty-year follow-up analysis. J Allergy Clin Immunol 1994; 94:954.
- Sherrill DL, Lebowitz MD, Halonen M, et al. Longitudinal evaluation of the association between pulmonary function and total serum IgE. Am J Respir Crit Care Med 1995; 152:98.
- Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002; 110:685.
- Burrows B, Martinez FD, Halonen M, et al. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 1989; 320:271.
- Tschopp JM, Sistek D, Schindler C, et al. Current allergic asthma and rhinitis: diagnostic efficiency of three commonly used atopic markers (IgE, skin prick tests, and Phadiatop). Results from 8329 randomized adults from the SAPALDIA Study. Swiss Study on Air Pollution and Lung Diseases in Adults. Allergy 1998; 53:608.
- Bañuelos Arias Adel C, Montaño Velázquez BB, Campillo Navarrete MR, et al. [Skin tests, serum specific IgE and total IgE in the diagnosis of patients with perennial allergic rhinitis]. Rev Alerg Mex 2003; 50:147.
- Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 2008; 100:S1.
- Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol 2008; 122:S1.
- Schmid-Grendelmeier P, Simon D, Simon HU, et al. Epidemiology, clinical features, and immunology of the "intrinsic" (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis). Allergy 2001; 56:841.
- Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol 2011; 41:298.
- Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 1998; 101:E8.
- NIAID-Sponsored Expert Panel, Boyce JA, Assa'ad A, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010; 126:S1.
- Golden DB, Moffitt J, Nicklas RA, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J Allergy Clin Immunol 2011; 127:852.
- Golden DB, Kagey-Sobotka A, Norman PS, et al. Insect sting allergy with negative venom skin test responses. J Allergy Clin Immunol 2001; 107:897.
- Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010; 105:259.
- Macy E, Goldberg B, Poon KY. Use of commercial anti-penicillin IgE fluorometric enzyme immunoassays to diagnose penicillin allergy. Ann Allergy Asthma Immunol 2010; 105:136.
- Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med 2013; 368:924.
- Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol 2013; 132:101.
- Hamilton RG, MacGlashan DW Jr, Saini SS. IgE antibody-specific activity in human allergic disease. Immunol Res 2010; 47:273.
- Mehl A, Verstege A, Staden U, et al. Utility of the ratio of food-specific IgE/total IgE in predicting symptomatic food allergy in children. Allergy 2005; 60:1034.
- Johansson SG, Nopp A, Oman H, et al. The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment. Allergy 2009; 64:1472.
- The atopic march
- RELATIONSHIPS BETWEEN TOTAL IgE LEVELS AND ALLERGIC DISEASE
- Elevated total serum IgE
- Low or normal levels of total serum IgE
- Utility in predicting the development of allergic disease
- - Cord blood
- - Childhood IgE levels
- - Timeline of sensitization
- THE ROLE OF IgE IN SPECIFIC DISORDERS
- - Lung function correlates with IgE
- Allergic bronchopulmonary aspergillosis
- Allergic rhinitis
- Atopic dermatitis
- - Food allergy
- Venom allergy
- Drug allergy
- Chronic urticaria
- RATIO OF ALLERGEN-SPECIFIC IgE TO TOTAL IgE