Predictive value of IgE/IgG4 antibody ratio in children with egg allergy

Allergy, Asthma & Clinical Immunology

Shindou Okamoto¹  Shoichiro Taniuchi¹  Kyoko Sudo¹  Yasuko Hatano¹  Keiji Nakano¹  Tomohiko Shimo¹  Kazunari Kaneko¹ 

[1] Department of Pediatrics, Kansai Medical University, Fumizonocho 10-15, Moriguchi, Osaka, 570-8506, Japan

关键词: Food challenge;    IgE;    egg white;    IgG₄;    Food allergy;   

Others  :  794820
DOI  :  10.1186/1710-1492-8-9

 received in 2012-01-04, accepted in 2012-05-18,  发布年份 2012

【 摘 要 】

Background

The aim of this study was to investigate the role of specific IgG₄ antibodies to hen’s egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen’s egg

Methods

The hen’s egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G₄ (IgG₄) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG₄, IgE, and the IgE/IgG₄ ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated.

Results

Sixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG₄, and IgE/IgG₄ for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG₄ ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG₄. The negative predictive value of the IgE/IgG₄ ratio was 90% at a value of 1.

Conclusions

We have demonstrated that the egg white-specific serum IgE/IgG₄ ratio is important for predicting reactivity to egg during food challenges.

【 授权许可】

   
2012 Okamoto et al.; licensee BioMed Central Ltd; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Ebisawa M: Management of food allergy in Japan food allergy management guideline 2008 (revision from 2005)”and “guide lines for the treatment of allergic diseases in schools. Allergol Int 2009, 58:475-483.
• [2]Sampson HA, Mendelson L, Rosen JP: Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992, 327:380-384.
• [3]Moneret-Vautrin DA, Kanny G: Update on threshold doses of food allergens: implications for patients and the food industry. Curr Opin Allergy Clin Immunol 2004, 4:215-219.
• [4]Sampson HA, Ho DG: Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. J Allergy Clin Immunol 1997, 100:444-451.
• [5]Sampson HA: Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001, 107:891-896.
• [6]Hill DJ, Hosking CS, Reyes-Benito LV: Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests. Clin Exp Allergy 2001, 31:1031-1035.
• [7]James JM, Sampson HA: Immunologic changes associated with the development of tolerance in children with cow milk allergy. J Pediatr 1992, 121:371-377.
• [8]Jenmalm MC, Björkstén B: Development of immunoglobulin G subclass antibodies to ovalbumin, birch and cat during the first eight years of life in atopic and non-atopic children. Pediatr Allergy Immunol 1999, 10:112-121.
• [9]Jenmalm MC, Björkstén B: Exposure to cow's milk during the first three months of life is associated with increased levels of IgG subclass antibodies to β-lactoglobulin up to eight years. J Allergy Clin Immunol 1998, 102:671-678.
• [10]Merrett J, Barnetson RS, Burr ML, Merrett TG: Total and specific IgG4 antibody levels in atopic eczema. Clin Exp Immunol 1984, 56:645-652.
• [11]Ishizaka A, Sakiyama Y, Nakanishi M, Tomizawa K, Oshika E, Kojima K: The inductive effect of interleukin 4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. Clin Exp Allergy 1990, 79:392-396.
• [12]Satoguina J, Weyand E, Larbi J, Hoerauf A: T regulatory-1 cells induce IgG4 production by B cells: role of IL-10. J Immunol 2005, 174:4718-4726.
• [13]Platts-Mills TAE, Vaughan J, Squillace S, Woodfolk J, Sporik R: Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 2001, 357:752-756.
• [14]Itoh N, Itagaki Y, Kurihara K: Rush specific oral tolerance induction in school-age children with severe egg allergy: one year follow up. Allergol Int 2010, 59:43-51.
• [15]Mousallem T, Burks AW: Immunology in the Clinic Review Series; focus on allergies: immunotherapy for food allergy. Clin Exp Immunol 2012, 167:26-31.
• [16]Savilahti EM, Rantanen V, Lin JS, Karinen S, Saarinen KM, Goldis M, Mäkelä MJ, Hautaniemi S, Savilahti E, Sampson HA: Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes. J Allergy Clin Immunol 2010, 125:1315-1321.
• [17]Tomicić S, Norrman G, Fälth-Magnusson K, Jenmalm MC, Devenney I, Böttcher MF: High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life. Pediatr Allergy Immunol 2009, 20:35-41.
• [18]Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M, Francis JM, Durham S, Vickery BP, Zhong X, Burks AW: Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 2009, 124:292-300.
• [19]May CD: Objective clinical and laboratory studies of immediate hypersensitivity reactions to foods in asthmatic children. J Allergy Clin Immunol 1976, 58:500-515.
• [20]Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M, Bush RK, Metcalfe DD: Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol 1988, 82:986-997.
• [21]Hill DJ, Hosking CS, Reyes-Benito LV: Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests. Clin Exp Allergy 2001, 31:1031-1035.
• [22]Sampson HA, Albergo R: Comparison of results of skin tests, RAST, and double-blind, placebo-controlled food challenges in children with atopic dermatitis. J Allergy Clin Immunol 1984, 74:26-33.
• [23]Boyano Martinez T, Garcia-Ara C, Diaz-Pena JM, Munoz FM, Garcia Sanchez G, Esteban MM: Validity of specific IgE antibodies in children with egg allergy. Clin Exp Allergy 2001, 31:1464-1469.
• [24]Osterballe M, Bindslev-Jensen C: Threshold levels in food challenge and specific IgE in patients with egg allergy: is there a relationship? J Allergy Clin Immunol 2003, 112:196-201.
• [25]Celik-Bilgili S, Mehl A, Verstege A, Staden U, Nocon M, Beyer K, Niggemann B: The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges. Clin Exp Allergy 2005, 35:268-273.
• [26]Ando H, Movérare R, Kondo Y, Tsuge I, Tanaka A, Borres MP, Urisu A: Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol 2008, 122:583-588.
• [27]Lue KH, Lin YH, Sun HL, Lu KH, Hsieh JC, Chou MC: Clinical and immunological effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study. Pediatr Allergy Immunol 2006, 17:408-415.
• [28]Ishizaka A, Sakiyama Y, Nakanishi M, Tomizawa K, Oshika E, Kojima K: The inductive effect of interleukin 4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. Clin Exp Allergy 1990, 79:392-396.
• [29]Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S, Vieths S, Kleine-Tebbe J: Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy 2008, 63:793-796.
• [30]Ruiter B, Knol EF, van Neerven RJ, Garssen J, Bruijnzeel-Koomen CA, Knulst AC, van Hoffen E: Maintenance of tolerance to cow’s milk in atopic individuals is characterized by high levels of specific immunoglobulin G4. Clin Exp Allergy 2007, 37:1103-1110.
• [31]Shek LP, Bardina L, Castro R, Sampson HA, Beyer K: Humoral and cellular responses to cow milk proteins in patients with milk-induced IgE-mediated and non-IgE-mediated disorders. Allergy 2005, 60:912-919.
• [32]Ahrens B, de Oliveira LC Lopes, Schulz G, Borres MP, Niggemann B, Wahn U, Beyer K: The role of hen’s egg-specific IgE, IgG and IgG4 in the diagnostic procedure of hen’s egg allergy. Allergy 2010, 65:1554-1557.
• [33]Oxelius VA: IgG subclass levels in infancy and childhood. Acta Paediatr Scand 1979, 68:23-27.