变应原特异性免疫治疗的研究进展
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摘要
变应原特异性免疫治疗(Allergen-specific immunotherapy, ASIT)是现阶段唯一针对病因治疗且能长时间持续减轻过敏症状,改变自然病程的治疗方法。目前已在过敏性疾病的临床治疗中广泛应用,并取得良好的治疗效果。随着治疗药物和治疗途径的不断改良,ASIT在过敏性疾病的治疗中显示出不可比拟的优势。本文对ASIT作用机制、应用药物、给药途径和禁忌症方面进行综述,旨在为ASIT的临床治疗提供参考。
Allergen-specific immunotherapy(ASIT) is the only treatment that causes a long-lasting relief of symptoms and change the natural course at this stage. This treatment has been widely applied in allergic diseases and achieved successful clinical outcomes. With the development of treatment, ASIT demonstrated unparalleled advantages of allergic diseases. This review summarizes the advances in the mechanisms of ASIT, the application of drug and route of administration to provide a reference for ASIT.
Allergen-specific immunotherapy(ASIT) is the only treatment that causes a long-lasting relief of symptoms and change the natural course at this stage. This treatment has been widely applied in allergic diseases and achieved successful clinical outcomes. With the development of treatment, ASIT demonstrated unparalleled advantages of allergic diseases. This review summarizes the advances in the mechanisms of ASIT, the application of drug and route of administration to provide a reference for ASIT.
引文
[1] Beasley R.The burden of asthma with specific reference to the United States[J].J Allergy Clin Immunol,2002,109(5 Suppl):S482-489.DOI:10.1067/mai.2002.122716
[2] Asher MI,Montefort S,Bjorksten B,et al.Worldwide time trends in the prevalence of symptoms of asthma,allergic rhinoconjunctivitis,and eczema in childhood:ISAAC Phases One and Three repeat multicountry cross-sectional surveys[J].Lancet,2006,368(9537):733-743.DOI:10.1016/S0140-6736(06)69283-0
[3] Lewkowich IP,Lajoie S,Clark JR,et al.Allergen uptake,activation,and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice[J].PLoS One,2008,3(12):e3879.DOI:10.1371/journal.pone.0003879
[4] Vargas MH,Diaz-Mejia GS,Furuya ME,et al.Trends of asthma in Mexico:an 11-year analysis in a nationwide institution[J].Chest,2004,125(6):1993-1997.DOI:10.1378/chest.125.6.1993
[5] Galli SJ,Tsai M,Piliponsky AM.The development of allergic inflammation[J].Nature,2008,454(7203):445-454.DOI:10.1038/nature07204
[6] Rachmiel M,Bloch O,Bistritzer T,et al.TH1/TH2 cytokine balance in patients with both type 1 diabetes mellitus and asthma[J].Cytokine,2006,34(3-4):170-176.DOI:10.1016/j.cyto.2006.04.012
[7] Ying L,Fu Z,Luo J,et al.Cytotoxic T lymphocyte antigen 4 immunoglobulin modified dendritic cells attenuate allergic airway inflammation and hyperresponsiveness by regulating the development of T helper type 1 (Th1)/Th2 and Th2/regulatory T cell subsets in a murine model of asthma[J].Clin Exp Immunol,2011,165(1):130-139.DOI:10.1111/j.1365-2249.2011.04405.x
[8] Siwiec J,Zaborowski T,Jankowska O,et al.Evaluation of Th1/Th2 lymphocyte balance and lipopolysaccharide receptor expression in asthma patients[J].Pneumonol Alergol Pol,2009,77(2):123-130.
[9] Simoes DC,Psarra AM,Mauad T,et al.Glucocorticoid and estrogen receptors are reduced in mitochondria of lung epithelial cells in asthma[J].PLoS One,2012,7(6):e39183.DOI:10.1371/journal.pone.0039183
[10] Keenan CR,Salem S,Fietz ER,et al.Glucocorticoid-resistant asthma and novel anti-inflammatory drugs[J].Drug Discov Today,2012,17(17-18):1031-1038.DOI:10.1016/j.drudis.2012.05.011
[11] Benedictis FM,Carloni I.Safety of long-acting beta2-agonists in asthma[J].Thorax,2012,67(11):1014-1015.DOI:10.1136/thoraxjnl-2012-201991
[12] Castro-Rodriguez JA,Rodrigo GJ.A systematic review of long-acting beta2-agonists versus higher doses of inhaled corticosteroids in asthma[J].Pediatrics,2012,130(3):e650-657.DOI:10.1542/peds.2012-0162
[13] Imai K,Munehisa Y,Yoshikuni Y,et al.Influences of pyrexia and age on theophylline clearance in young children with asthma[J].Hiroshima J Med Sci,2012,61(1):15-18.
[14] Wang Y,Lin K,Wang C,et al.Addition of theophylline or increasing the dose of inhaled corticosteroid in symptomatic asthma:a meta-analysis of randomized controlled trials[J].Yonsei Med J,2011,52(2):268-275.DOI:10.3349/ymj.2011.52.2.268
[15] Jacobsen L,Wahn U,Bilo MB.Allergen-specific immunotherapy provides immediate,long-term and preventive clinical effects in children and adults:the effects of immunotherapy can be categorised by level of benefit-the centenary of allergen specific subcutaneous immunotherapy[J].Clin Transl Allergy,2012,2 (13):8-19.DOI:10.1186/2045-7022-2-8
[16] Till SJ,Francis JN,Nouri-Aria K,et al.Mechanisms of immunotherapy[J].J Allergy Clin Immunol,2004,113(6):1025-1034.DOI:10.1016/j.jaci.2004.03.024
[17] Bousquet J,Lockey R,Malling HJ.Allergen immunotherapy:therapeutic vaccines for allergic diseases.A WHO position paper[J].J Allergy Clin Immunol,1998,102(4 Pt 1):558-562.DOI:10.1111/j.1398-9995.1998.tb04930.x
[18] Rael E.Allergen Immunotherapy[J].Prim Care,2016,43(3):487-494.DOI:10.1016/j.pop.2016.04.004.
[19] Fujita H,Soyka MB,Akdis M,et al.Mechanisms of allergen-specific immunotherapy[J].Clin Transl Allergy,2012,2(1):2.DOI:10.1186/2045-7022-2-2
[20] Mitsias DI,Savvatianos S,Papadopoulos NG.An insight into the early mechanisms of allergen-specific immunotherapy[J].Immunotherapy,2011,3(3):333-336.DOI:10.2217/imt.10.112
[21] Larche M,Akdis CA,Valenta R.Immunological mechanisms of allergen-specific immunotherapy[J].Nat Rev Immunol,2006,6(10):761-771.DOI:10.1038/nri1934
[22] 陶绮蕾,程雷.儿童变应性鼻炎的特异性免疫治疗[J].中华耳鼻咽喉头颈外科杂志,2012,47(8):694-698.DOI:10.3760/cma.j.issn.1673-0860.2012.08.022
[23] Focke-Tejkl M,Valenta R.Safety of engineered allergen-specific immunotherapy vaccines[J].Curr Opin Allergy Clin Immunol,2012,12(5):555-563.DOI:10.1097/ACI.0b013e328357ca53
[24] Moote W,Kim H.Allergen-specific immunotherapy[J].Allergy Asthma Clin Immunol,2011,7 Suppl 1:S5.DOI:10.1186/1710-1492-7-S1-S5
[25] El S-C,Poelt P,Aberer W,et al.Progressive circumscribed sclerosis--a novel side-effect of immunotherapy with aluminium-adsorbed allergen extracts[J].Allergy,2009,64(6):965-967.DOI:10.1111/j.1398-9995.2009.01999.x
[26] Ball T,Sperr WR,Valent P,et al.Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy[J].Eur J Immunol,1999,29(6):2026-2036.DOI:10.1002/(SICI)1521-4141(199906)29:06<2026::AID-IMMU2026>3.0.CO;2-2
[27] Moverare R,Elfman L,Vesterinen E,et al.Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP System[J].Allergy,2002,57(5):423-430.DOI:10.1034/j.1398-9995.2002.13248.x
[28] Govindaraj D,Gaur SN,Arora N.Characterization of recombinant Per a 10,from Periplaneta americana[J].Clin Vaccine Immunol,2013,20(2):262-268.DOI:10.1128/CVI.00461-12
[29] Myrset HR,Barletta B,Di Felice G,et al.Structural and Immunological Characterization of Recombinant Pan b 1,a Major Allergen of Northern Shrimp,Pandalus borealis[J].Int Arch Allergy Immunol,2012,160(3):221-232.DOI:10.1159/000339740
[30] Bordas-Le Floch V,Bussieres L,Airouche S,et al.Expression and characterization of natural-like recombinant Der p 2 for sublingual immunotherapy[J].Int Arch Allergy Immunol,2012,158(2):157-167.DOI:10.1159/000331143
[31] 郭伟,姜玉新,李朝品.两种尘螨1类变应原嵌合基因的原核表达及生物活性鉴定[J].中国寄生虫学与寄生虫病杂志,2012,30(4):274-278.
[32] Gafvelin G,Parmley S,Neimert-Andersson T,et al.Hypoallergens for allergen-specific immunotherapy by directed molecular evolution of mite group 2 allergens[J].J Biol Chem,2007,282(6):3778-3787.DOI:10.1074/jbc.M607938200
[33] Wallner M,Stocklinger A,Thalhamer T,et al.Allergy multivaccines created by DNA shuffling of tree pollen allergens[J].J Allergy Clin Immunol,2007,120(2):374-380.DOI:10.1016/j.jaci.2007.05.021
[34] Scheiblhofer S,Stoecklinger A,Gruber C,et al.Gene gun immunization with clinically relevant allergens aggravates allergen induced pathology and is contraindicated for allergen immunotherapy[J].Mol Immunol,2007,44(8):1879-1887.DOI:10.1016/j.molimm.2006.09.023
[35] Li G,Liu Z,Zhong N,et al.Therapeutic effects of DNA vaccine on allergen-induced allergic airway inflammation in mouse model[J].Cell Mol Immunol,2006,3(5):379-384.DOI:10.1016/j.cellimm.2006.05.009
[36] Hartl A,Hochreiter R,Stepanoska T,et al.Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a[J].Allergy,2004,59(1):65-73.DOI:10.1046/j.1398-9995.2003.00335.x
[37] Wang Y,Qian G,Wang G,et al.Potential therapy of Fc-antigen combination-encoding DNA vaccination in mouse allergic airway inflammation[J].Clin Exp Immunol,2008,154(1):115-122.DOI:10.1111/j.1365-2249.2008.03736.x
[38] Larche M.Immunoregulation by targeting T cells in the treatment of allergy and asthma[J].Curr Opin Immunol,2006,18(6):745-750.DOI:10.1016/j.coi.2006.09.013
[39] Niederberger V,Horak F,Vrtala S,et al.Vaccination with genetically engineered allergens prevents progression of allergic disease[J].Proc Natl Acad Sci U S A,2004,101 Suppl 2:14677-14682.DOI:10.1073/pnas.0404735101
[40] Jutel M,Jaeger L,Suck R,et al.Allergen-specific immunotherapy with recombinant grass pollen allergens[J].J Allergy Clin Immunol,2005,116(3):608-613.DOI:10.1016/j.jaci.2005.06.004
[41] Kundig TM,Senti G,Schnetzler G,et al.Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults[J].J Allergy Clin Immunol,2006,117(6):1470-1476.DOI:10.1016/j.jaci.2006.01.040
[42] Rotiroti G,Shamji M,Durham SR,et al.Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses[J].J Allergy Clin Immunol,2012,130(4):918-924.DOI:10.1016/j.jaci.2012.06.052
[43] Esposito S,Daleno C,Picciolli I,et al.Immunogenicity and safety of intradermal influenza vaccine in children[J].Vaccine,2011,29(44):7606-7610.DOI:10.1016/j.vaccine.2011.08.021
[44] Fleischer DM,Burks AW,Vickery BP,et al.Sublingual immunotherapy for peanut allergy:A randomized,double-blind,placebo-controlled multicenter trial[J].J Allergy Clin Immunol,2013,131(1):119-127.DOI:10.1016/j.jaci.2012.11.011
[45] Yamada T,Tongu M,Goda K,et al.Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4(+)CD25(+)Foxp3(+) T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model[J].J Allergy (Cairo),2012,2012:490905.DOI:10.1155/2012/490905
[46] Toda M,Kasai M,Hosokawa H,et al.DNA vaccine using invariant chain gene for delivery of CD4+ T cell epitope peptide derived from Japanese cedar pollen allergen inhibits allergen-specific IgE response[J].Eur J Immunol,2002,32(6):1631-1639.DOI:10.1002/1521-4141(200206)32:6<1631::AID-IMMU1631>3.0.CO;2-O
[47] Johansen P,Haffner AC,Koch F,et al.Direct intralymphatic injection of peptide vaccines enhances immunogenicity[J].Eur J Immunol,2005,35(2):568-574.DOI:10.1002/eji.200425599
[48] Cox L,Nelson H,Lockey R,et al.Allergen immunotherapy:a practice parameter third update[J].J Allergy Clin Immunol,2011,127(1 Suppl):S1-55.DOI:10.1016/j.jaci.2010.09.034
[49] Lang DM,Alpern MB,Visintainer PF,et al.Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders[J].Arch Intern Med,1993,153(17):2033-2040.DOI:10.1001/archinte.1993.00410170119012
[2] Asher MI,Montefort S,Bjorksten B,et al.Worldwide time trends in the prevalence of symptoms of asthma,allergic rhinoconjunctivitis,and eczema in childhood:ISAAC Phases One and Three repeat multicountry cross-sectional surveys[J].Lancet,2006,368(9537):733-743.DOI:10.1016/S0140-6736(06)69283-0
[3] Lewkowich IP,Lajoie S,Clark JR,et al.Allergen uptake,activation,and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice[J].PLoS One,2008,3(12):e3879.DOI:10.1371/journal.pone.0003879
[4] Vargas MH,Diaz-Mejia GS,Furuya ME,et al.Trends of asthma in Mexico:an 11-year analysis in a nationwide institution[J].Chest,2004,125(6):1993-1997.DOI:10.1378/chest.125.6.1993
[5] Galli SJ,Tsai M,Piliponsky AM.The development of allergic inflammation[J].Nature,2008,454(7203):445-454.DOI:10.1038/nature07204
[6] Rachmiel M,Bloch O,Bistritzer T,et al.TH1/TH2 cytokine balance in patients with both type 1 diabetes mellitus and asthma[J].Cytokine,2006,34(3-4):170-176.DOI:10.1016/j.cyto.2006.04.012
[7] Ying L,Fu Z,Luo J,et al.Cytotoxic T lymphocyte antigen 4 immunoglobulin modified dendritic cells attenuate allergic airway inflammation and hyperresponsiveness by regulating the development of T helper type 1 (Th1)/Th2 and Th2/regulatory T cell subsets in a murine model of asthma[J].Clin Exp Immunol,2011,165(1):130-139.DOI:10.1111/j.1365-2249.2011.04405.x
[8] Siwiec J,Zaborowski T,Jankowska O,et al.Evaluation of Th1/Th2 lymphocyte balance and lipopolysaccharide receptor expression in asthma patients[J].Pneumonol Alergol Pol,2009,77(2):123-130.
[9] Simoes DC,Psarra AM,Mauad T,et al.Glucocorticoid and estrogen receptors are reduced in mitochondria of lung epithelial cells in asthma[J].PLoS One,2012,7(6):e39183.DOI:10.1371/journal.pone.0039183
[10] Keenan CR,Salem S,Fietz ER,et al.Glucocorticoid-resistant asthma and novel anti-inflammatory drugs[J].Drug Discov Today,2012,17(17-18):1031-1038.DOI:10.1016/j.drudis.2012.05.011
[11] Benedictis FM,Carloni I.Safety of long-acting beta2-agonists in asthma[J].Thorax,2012,67(11):1014-1015.DOI:10.1136/thoraxjnl-2012-201991
[12] Castro-Rodriguez JA,Rodrigo GJ.A systematic review of long-acting beta2-agonists versus higher doses of inhaled corticosteroids in asthma[J].Pediatrics,2012,130(3):e650-657.DOI:10.1542/peds.2012-0162
[13] Imai K,Munehisa Y,Yoshikuni Y,et al.Influences of pyrexia and age on theophylline clearance in young children with asthma[J].Hiroshima J Med Sci,2012,61(1):15-18.
[14] Wang Y,Lin K,Wang C,et al.Addition of theophylline or increasing the dose of inhaled corticosteroid in symptomatic asthma:a meta-analysis of randomized controlled trials[J].Yonsei Med J,2011,52(2):268-275.DOI:10.3349/ymj.2011.52.2.268
[15] Jacobsen L,Wahn U,Bilo MB.Allergen-specific immunotherapy provides immediate,long-term and preventive clinical effects in children and adults:the effects of immunotherapy can be categorised by level of benefit-the centenary of allergen specific subcutaneous immunotherapy[J].Clin Transl Allergy,2012,2 (13):8-19.DOI:10.1186/2045-7022-2-8
[16] Till SJ,Francis JN,Nouri-Aria K,et al.Mechanisms of immunotherapy[J].J Allergy Clin Immunol,2004,113(6):1025-1034.DOI:10.1016/j.jaci.2004.03.024
[17] Bousquet J,Lockey R,Malling HJ.Allergen immunotherapy:therapeutic vaccines for allergic diseases.A WHO position paper[J].J Allergy Clin Immunol,1998,102(4 Pt 1):558-562.DOI:10.1111/j.1398-9995.1998.tb04930.x
[18] Rael E.Allergen Immunotherapy[J].Prim Care,2016,43(3):487-494.DOI:10.1016/j.pop.2016.04.004.
[19] Fujita H,Soyka MB,Akdis M,et al.Mechanisms of allergen-specific immunotherapy[J].Clin Transl Allergy,2012,2(1):2.DOI:10.1186/2045-7022-2-2
[20] Mitsias DI,Savvatianos S,Papadopoulos NG.An insight into the early mechanisms of allergen-specific immunotherapy[J].Immunotherapy,2011,3(3):333-336.DOI:10.2217/imt.10.112
[21] Larche M,Akdis CA,Valenta R.Immunological mechanisms of allergen-specific immunotherapy[J].Nat Rev Immunol,2006,6(10):761-771.DOI:10.1038/nri1934
[22] 陶绮蕾,程雷.儿童变应性鼻炎的特异性免疫治疗[J].中华耳鼻咽喉头颈外科杂志,2012,47(8):694-698.DOI:10.3760/cma.j.issn.1673-0860.2012.08.022
[23] Focke-Tejkl M,Valenta R.Safety of engineered allergen-specific immunotherapy vaccines[J].Curr Opin Allergy Clin Immunol,2012,12(5):555-563.DOI:10.1097/ACI.0b013e328357ca53
[24] Moote W,Kim H.Allergen-specific immunotherapy[J].Allergy Asthma Clin Immunol,2011,7 Suppl 1:S5.DOI:10.1186/1710-1492-7-S1-S5
[25] El S-C,Poelt P,Aberer W,et al.Progressive circumscribed sclerosis--a novel side-effect of immunotherapy with aluminium-adsorbed allergen extracts[J].Allergy,2009,64(6):965-967.DOI:10.1111/j.1398-9995.2009.01999.x
[26] Ball T,Sperr WR,Valent P,et al.Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy[J].Eur J Immunol,1999,29(6):2026-2036.DOI:10.1002/(SICI)1521-4141(199906)29:06<2026::AID-IMMU2026>3.0.CO;2-2
[27] Moverare R,Elfman L,Vesterinen E,et al.Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP System[J].Allergy,2002,57(5):423-430.DOI:10.1034/j.1398-9995.2002.13248.x
[28] Govindaraj D,Gaur SN,Arora N.Characterization of recombinant Per a 10,from Periplaneta americana[J].Clin Vaccine Immunol,2013,20(2):262-268.DOI:10.1128/CVI.00461-12
[29] Myrset HR,Barletta B,Di Felice G,et al.Structural and Immunological Characterization of Recombinant Pan b 1,a Major Allergen of Northern Shrimp,Pandalus borealis[J].Int Arch Allergy Immunol,2012,160(3):221-232.DOI:10.1159/000339740
[30] Bordas-Le Floch V,Bussieres L,Airouche S,et al.Expression and characterization of natural-like recombinant Der p 2 for sublingual immunotherapy[J].Int Arch Allergy Immunol,2012,158(2):157-167.DOI:10.1159/000331143
[31] 郭伟,姜玉新,李朝品.两种尘螨1类变应原嵌合基因的原核表达及生物活性鉴定[J].中国寄生虫学与寄生虫病杂志,2012,30(4):274-278.
[32] Gafvelin G,Parmley S,Neimert-Andersson T,et al.Hypoallergens for allergen-specific immunotherapy by directed molecular evolution of mite group 2 allergens[J].J Biol Chem,2007,282(6):3778-3787.DOI:10.1074/jbc.M607938200
[33] Wallner M,Stocklinger A,Thalhamer T,et al.Allergy multivaccines created by DNA shuffling of tree pollen allergens[J].J Allergy Clin Immunol,2007,120(2):374-380.DOI:10.1016/j.jaci.2007.05.021
[34] Scheiblhofer S,Stoecklinger A,Gruber C,et al.Gene gun immunization with clinically relevant allergens aggravates allergen induced pathology and is contraindicated for allergen immunotherapy[J].Mol Immunol,2007,44(8):1879-1887.DOI:10.1016/j.molimm.2006.09.023
[35] Li G,Liu Z,Zhong N,et al.Therapeutic effects of DNA vaccine on allergen-induced allergic airway inflammation in mouse model[J].Cell Mol Immunol,2006,3(5):379-384.DOI:10.1016/j.cellimm.2006.05.009
[36] Hartl A,Hochreiter R,Stepanoska T,et al.Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a[J].Allergy,2004,59(1):65-73.DOI:10.1046/j.1398-9995.2003.00335.x
[37] Wang Y,Qian G,Wang G,et al.Potential therapy of Fc-antigen combination-encoding DNA vaccination in mouse allergic airway inflammation[J].Clin Exp Immunol,2008,154(1):115-122.DOI:10.1111/j.1365-2249.2008.03736.x
[38] Larche M.Immunoregulation by targeting T cells in the treatment of allergy and asthma[J].Curr Opin Immunol,2006,18(6):745-750.DOI:10.1016/j.coi.2006.09.013
[39] Niederberger V,Horak F,Vrtala S,et al.Vaccination with genetically engineered allergens prevents progression of allergic disease[J].Proc Natl Acad Sci U S A,2004,101 Suppl 2:14677-14682.DOI:10.1073/pnas.0404735101
[40] Jutel M,Jaeger L,Suck R,et al.Allergen-specific immunotherapy with recombinant grass pollen allergens[J].J Allergy Clin Immunol,2005,116(3):608-613.DOI:10.1016/j.jaci.2005.06.004
[41] Kundig TM,Senti G,Schnetzler G,et al.Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults[J].J Allergy Clin Immunol,2006,117(6):1470-1476.DOI:10.1016/j.jaci.2006.01.040
[42] Rotiroti G,Shamji M,Durham SR,et al.Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses[J].J Allergy Clin Immunol,2012,130(4):918-924.DOI:10.1016/j.jaci.2012.06.052
[43] Esposito S,Daleno C,Picciolli I,et al.Immunogenicity and safety of intradermal influenza vaccine in children[J].Vaccine,2011,29(44):7606-7610.DOI:10.1016/j.vaccine.2011.08.021
[44] Fleischer DM,Burks AW,Vickery BP,et al.Sublingual immunotherapy for peanut allergy:A randomized,double-blind,placebo-controlled multicenter trial[J].J Allergy Clin Immunol,2013,131(1):119-127.DOI:10.1016/j.jaci.2012.11.011
[45] Yamada T,Tongu M,Goda K,et al.Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4(+)CD25(+)Foxp3(+) T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model[J].J Allergy (Cairo),2012,2012:490905.DOI:10.1155/2012/490905
[46] Toda M,Kasai M,Hosokawa H,et al.DNA vaccine using invariant chain gene for delivery of CD4+ T cell epitope peptide derived from Japanese cedar pollen allergen inhibits allergen-specific IgE response[J].Eur J Immunol,2002,32(6):1631-1639.DOI:10.1002/1521-4141(200206)32:6<1631::AID-IMMU1631>3.0.CO;2-O
[47] Johansen P,Haffner AC,Koch F,et al.Direct intralymphatic injection of peptide vaccines enhances immunogenicity[J].Eur J Immunol,2005,35(2):568-574.DOI:10.1002/eji.200425599
[48] Cox L,Nelson H,Lockey R,et al.Allergen immunotherapy:a practice parameter third update[J].J Allergy Clin Immunol,2011,127(1 Suppl):S1-55.DOI:10.1016/j.jaci.2010.09.034
[49] Lang DM,Alpern MB,Visintainer PF,et al.Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders[J].Arch Intern Med,1993,153(17):2033-2040.DOI:10.1001/archinte.1993.00410170119012