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1 5 7 Vol. 5 No Journal of Food Safety and Quality Jul., 2014 李兴永 1, 王巍 1, 孙宏治 1 1,, 杨平常 2, 刘志刚 (1., ; 2., ) 1, 2* 摘要 :, IgE( E) IgE,, IgE ( ) ( ),, 关键词 : ; ; ; ; Advances in pathogenesis, diagnosis and treatment strategies of food allergy LI Xing-Yong 1, WANG Wei 1, SUN Hong-Zhi 1, YANG Ping-Chang 1, 2 1, 2*, LIU Zhi-Gang (1. First Affiliated Hospital of Liaoning Medical University, Jinzhou , China; 2. Institute of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen , China) ABSTRACT: With the increasing diversity of food, food allergy incidence increased year by year and had become an increasingly concerned issue of the world public health. Food allergy may be IgE or non-ige mediated, including anaphylaxis, pollen food syndrome, food-protein induced enterocolitis syndrome, eosinophilic gastroenteropathies, and atopic dermatitis, which IgE-mediated hypersensitivity is most common in food allergy. Food allergens consist of major and minor allergens, which is usually protein or glycoprotein. Many complex body factors (such as immune tolerance, genetic and gastrointestinal factors) and properties of food allergens (such as epitope and thermal denaturation) are involved in the development of food allergy. With deepening research of how these factors interact and pathogenesis, several novel diagnostic and therapeutic strategies are underway and developing, which is significant for finding effectively induvidualized and standardized strategies of diagnosis, prevention and treatment. KEY WORDS: food allergy; immune tolerance; diagnosis; immunotherapy; advance 基金项目 : ( ) (2012gjhz0009) (GJHZ ) Fund: Supported by National Natural Science Foundation of China ( ), Project of Internation as well as Hongkong, Macao & Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province (2012gjhz0009), International Science and Technology Cooperation Project in Shenzhen (GJHZ ) * 通讯作者 :,,. lzg@szu.edu.cn *Corresponding author: LIU Zhi-Gang, Professor, Institute of Allergy and Immunology, Shenzhen University School of Medicine. No.3688, Nanhai Road, Nanshan, Shenzhen , China. lzg@szu.edu.cn

Ping-Chang 1, 2 1, 2*, LIU Zhi-Gang (1. First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China; 2.

2 引言, IgE IgE, IgE, 170 IgE, 90% [1],, 6.56%, 3.49%,, [2], [3],,,, 2 食物过敏发病机制的研究进展 2.1 食物过敏的免疫耐受机制 IgE ( ), IgE ( ),,, Th2,,, DC T T, DC T T, T [4], DC, T (Treg ) CD8 + Th3 Tr1 CD4 + CD25 + T T (NKT ), T IL-10 TGF-β Fas, FOXP3+ T γδ T NKT [5],, (TSLP) TSLP Th2,, [6], TSLP, Th2,, TSLP (EOE) [7], IgE IgE T 2.2 食物过敏患者的胃肠道因素,, Otani [8] IL-9, 10 [9] 4-6,, [10,11], (EOE) [12] ph 152 3, 25% [13],,,,, 2.3 食物过敏原因素食物过敏原的序列和构象表位因素,, ( ) [14] IgE IgE,,, IgE, IgE, IgA IgG,,

IL-10 TGF-β Fas, FOXP3+ T γδ T NKT [5],, (TSLP) TSLP Th2,, [6], TSLP, Th2,, TSLP (EOE) [7], IgE IgE T 2.

3 7, : 2135 [15] 食物过敏原的热变性 73% 80% [16,17],,, (OVA) [18] Arah1 Th2 DC Th2, IgE, Commins [19] -α-1, 3- (α- ), 2.4 其他因素, ( β ) [20], (PAF-AH), PAF-AH [21] 3 食物过敏诊治的研究进展 3.1 食物过敏的诊断 [22] IgE (SPT) IgE (sige),, IgE (APT), [23] (SPT sige), [24] [25] [26],, [27] 3.2 食物过敏的预防和治疗,,,, 过敏原特异性疗法, (SCIT) 1908 (OIT), Skripak [28] OIT, OIT, Jones [29] OIT, 93% IgE IgG4 OIT,, OIT 3.5% [30] ; OIT, 6, OIT [31] (SLIT), 5-6,, [32], OIT SLIT,, IgE,, Arah1-3, T, IgE T DNA,, 过敏原非特异性疗法 IgE, Omalizumab [33] IgE IgE FcεRI,, IgE,, I Omalizumab IgE FcεRI, IgE, I

1 食物过敏的诊断 [22] IgE (SPT) IgE (sige),, IgE (APT), [23] (SPT sige), [24] [25] [26],, [27] 3.2 食物过敏的预防和治疗,,,, 3.2.1 过敏原特异性疗法, (SCIT) 1908 (OIT), Skripak [28] OIT, OIT, Jones [29] OIT, 93% IgE IgG4 OIT,, OIT 3.

4 2136 5, Canakinumab [34] ( IL-1 ),, Formula-2(FAHF -2), 9,, FAHF-2, IgE, Th2 IL-4 IL-5 IL-13, IFN-γ CD8 + T [35] FAHF-2, FAHF-2 T, Th2, IFN-γ,, FAHF-2,, [36] Th1 Th2, Th1 4 总结,,, 参考文献 [1] Boyce JA, Assaad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel [J]. J Allergy Clin Immunol, 2011, 31(1): [2] McGowan EC, Keet CA. Prevalence of self-reported food allergy in the National Health and Nutrition Examination Survey (NHANES) [J]. J Allergy Clin Immunol, 2013, 132(5): [3] Gupta R, Holdford D, Bilaver L, et al. The economic impact of childhood food allergy in the United States [J]. JAMA Pediatr, 2013, 167(11): [4] Ilan Y. Oral tolerance: can we make it work? [J]. Hum Immunol, 2009, 70(10): [5] Bol-Schoenmakers M, Pieters RH, Smit JJ, et al. Regulation by intestinal gd T cells during establishment of food allergic sensitization in mice 2010 [J]. Allergy, 2011, 66(3): [6] Demehri S, Morimoto M, Holtzman MJ, et al. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma [J]. PLoS Biol, 2009, 7(5): e [7] Sherrill JD, Gao PS, Stucke EM, et al. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis [J]. J Allergy Clin Immunol, 2010, 126(1): [8] Otani IM, Anilkumar AA, Newbury RO, et al. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis [J]. J Allergy Clin Immunol, 2013, 131(6): [9] Du Toit G, Katz Y, Sasieni P, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy [J]. J Allergy Clin Immunol, 2008, 122(5): [10] Katz Y, Cohen A, Leshno M, et al. Early exposure to cow s milk protein is protective against IgE-mediated cow s milk protein allergy [J]. J Allergy Clin Immunol, 2010, 126(1): [11] Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study [J]. J Allergy Clin Immunol, 2010, 126(4): [12] Greenhawt M, Aceves SS, Spergel JM, et al. The management of eosinophilic esophagitis [J]. J Allergy Clin Immunol Pract, 2013, 1(4): [13] Untersmayr E, Bakos N, Kundi M, et al. Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients [J]. FASEB J, 2005, 19(6): [14] Sicherer SH, Sampson HA. Food allergy:epidemiology, pathogenesis, diagnosis, and treatment [J]. J Allergy Clin Immunol, 2010, 133(2): [15] Sicherer SH, Leung DY. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013 [J]. J Allergy Clin Immunol, 2014, 133(2): [16] Lemon-Mule H, Sampson HA, Sicherer SH, et al. Immunologic changes in children with egg allergy ingesting extensively heated egg [J]. J Allergy Clin Immunol, 2008, 122(5): [17] Leung J, Hundal NV, Katz AJ, et al. Tolerance of baked milk in patients with cow s milk-mediated eosinophilic esophagitis [J]. J Allergy Clin Immunol, 2013, 132(5): [18] Hilmenyuk T, Grabbe S, Saloga J, et al. Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells [J]. Immunology, 2010, 129(3): [19] Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema,or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose [J]. J Allergy Clin Immunol, 2009, 123(2): [20] Bock SA, Munoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, [J]. J Allergy Clin Immunol, 2007, 119(4): [21] Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase,and severe anaphylaxis [J]. N Engl J Med, 2008, 358(1): [22] Bergmann MM, Caubet JC, Boguniewicz M, et al. Evaluation of food allergy in patients with atopic dermatitis [J]. J Allergy Clin Immunol Pract, 2013, 1(1): [23] Turjanmaa K, Darsow U, Niggemann B, et al. EAACI/GA2LEN position paper: Present status of the atopy patch test[j]. Allergy, 2006, 61(12):

J Allergy Clin Immunol, 2011, 31(1): 61 75. [2] McGowan EC, Keet CA. Prevalence of self-reported food allergy in the National Health and Nutrition Examination Survey (NHANES) 2007-2010 [J].

5 7, : 2137 [24] Pahr S, Makela M, Pelkonen A, et al. Alpha-Purothionin, a new wheat allergen associated with severe allergy [J]. J Allergy Clin Immunol, 2013, 132(4): [25] Ebisawa M, Brostedt P, Sjolander S, et al. Gly m 2S albumin is a major allergen with a high diagnostic value in soybean-allergic children [J]. J Allergy Clin Immunol, 2013, 132(4): [26] Masthoff LJ, Mattsson L, Lidholm J, et al. Sensitization to Cor a 9 and Cor a 14 is highly specificfor a hazelnut allergy with objective symptoms in Dutch children and adults [J]. J Allergy Clin Immunol, 2013, 132(2): [27] Wanich N, Nowak-Wegrzyn A, Sampson HA, et al. Allergen-specific basophil suppression associated with clinical tolerance in patients with milk allergy [J]. J Allergy Clin Immunol, 2009, 123(4): [28] Skripak JM, Nash SD, Rowley H, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow s milk allergy [J]. J Allergy Clin Immunol, 2008, 122(6): [29] Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy [J]. J Allergy Clin Immunol, 2009, 124(2): [30] Varshney P, Steele PH, Vickery BP, et al. Adverse reactions during peanut oral immunotherapy home dosing [J]. J Allergy Clin Immunol, 2009, 124(6): [31] Narisety SD, Skripak JM, Steele P, et al. Open-label maintenance after milk oral immunotherapy for IgE-mediated cow s milk allergy [J]. J Allergy Clin Immunol, 2009, 124(3): [32] Fernandez-Rivas M, Rico P, Tabar AI, et al. Randomized doubleblind,placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract [J]. Allergy, 2009, 64(6): [33] Sampson HA, Leung DY, Burks AW, et al. A phase II, randomized, double-blind,parallel group, placebo-controlled oral food challenge trial of Xolair (omalizumab) in peanut allergy [J]. J Allergy Clin Immunol, 2010, 127(5): [34] Krause K, Mahamed A, Weller K, et al. Efficacy and safety of canakinumab in urticarial vasculitis: an open-label study [J]. J Allergy Clin Immunol, 2013, 132(3): [35] Srivastava KD, Qu C, Li XM, et al. Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-gammaproducing CD8+ T cells [J]. J Allergy Clin Immunol, 2009, 123(2): [36] Song Y, Dunkin D, Dahan S, et al. Anti-inflammatory effects of the Chinese herbal formula FAHF-2 in experimental and human IBD [J]. Inflamm Bowel Dis, 2014, 20(1): 作者简介 ( 责任编辑 : 张宏梁 ) 李兴永, 硕士生, 主要研究方向为消化道肿瘤与食物过敏的研究 lxylnmu@126.com 刘志刚, 教授, 博士生导师, 主要研究方向为过敏性疾病过敏原的基础研究和过敏原疫苗的研究 lzg@szu.edu.cn

[26] Masthoff LJ, Mattsson L, Lidholm J, et al. Sensitization to Cor a 9 and Cor a 14 is highly specificfor a hazelnut allergy with objective symptoms in Dutch children and adults [J].

by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (2

by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (2 论著临床研究 doi: 0.7499/j.issn.008-8830.204.2.007 郑州市城区儿童哮喘的流行病学调查及发病相关因素分析赵坤宋桂华古华倩 2 刘爽 3 张岩郭彦荣 (. 河南中医学院第一附属医院儿科医院, 河南郑州 450000; 2. 杭州市余杭区