Sublingual immunotherapy for peanut allergy: Clinical and immunologic evidence of desensitization

被引:280
作者
Kim, Edwin H. [1 ]
Bird, J. Andrew [1 ]
Kulis, Michael [1 ]
Laubach, Susan [1 ]
Pons, Laurent [1 ]
Shreffler, Wayne [2 ]
Steele, Pamela [1 ]
Kamilaris, Janet [1 ]
Vickery, Brian [1 ]
Burks, A. Wesley [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA
[2] Massachusetts Gen Hosp, Food Allergy Ctr MGH, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA
基金
美国国家卫生研究院;
关键词
Peanut allergy; sublingual immunotherapy; desensitization; food allergy; ANAPHYLACTIC REACTIONS; FOOD ALLERGY; DOUBLE-BLIND; KIWI FRUIT; FATALITIES;
D O I
10.1016/j.jaci.2010.12.1083
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: There are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy. Objective: We sought to investigate the safety, clinical effectiveness, and immunologic changes with SLIT in children with peanut allergy. Methods: In this double-blind, placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge. Results: Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median, 1,710 vs 85 mg; P = .011). Mechanistic studies demonstrated a decrease in skin prick test wheal size (P = .020) and decreased basophil responsiveness after stimulation with 10(-2) mu g/mL (P = .009) and 10(-3) mu g/mL (P = .009) of peanut. Peanut-specific IgE levels increased over the initial 4 months (P = .002) and then steadily decreased over the remaining 8 months (P = .003), whereas peanut-specific IgG4 levels increased during the 12 months (P = .014). Lastly, IL-5 levels decreased after 12 months (P = .015). No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-gamma production. Conclusion: Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy, with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance. (J Allergy Clin Immunol 2011;127:640-6.)
引用
收藏
页码:640 / U153
页数:8
相关论文
共 26 条
[1]   T regulatory cells in allergy: Novel concepts in the pathogenesis, prevention, and treatment of allergic diseases [J].
Akdis, M ;
Blaser, K ;
Akdis, CA .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 116 (05) :961-968
[2]   Mechanisms of allergen-specific immunotherapy [J].
Akdis, Muebeccel ;
Akdis, Cezmi A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (04) :780-789
[3]   Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells [J].
Allam, Jean-Pierre ;
Peng, Wen-Ming ;
Appel, Torsten ;
Wenghoefer, Matthias ;
Niederhagen, Bernd ;
Bieber, Thomas ;
Berg, Stefaan ;
Novak, Natalija .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 121 (02) :368-374
[4]   Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-β1 and IL-10-producing properties [J].
Allam, Jean-Pierre ;
Wuertzen, Peter A. ;
Reinartz, Markus ;
Winter, Jochen ;
Vrtala, Susanne ;
Chen, Kuan-Wei ;
Valenta, Rudolf ;
Wenghoefer, Matthias ;
Appel, Thorsten ;
Gros, Eva ;
Niederhagen, Bernd ;
Bieber, Thomas ;
Lund, Kaare ;
Novak, Natalija .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 126 (03) :638-U5
[5]   Oral rush desensitization to milk [J].
Bauer, A ;
Ekanayake-Mudiyanselage, S ;
Wigger-Alberti, W ;
Elsner, P .
ALLERGY, 1999, 54 (08) :894-895
[6]   Oral peanut immunotherapy in children with peanut anaphylaxis [J].
Blumchen, Katharina ;
Ulbricht, Helen ;
Staden, Ute ;
Dobberstein, Kerstin ;
Beschorner, John ;
de Oliveira, Lucila Camargo Lopes ;
Shreffler, Wayne G. ;
Sampson, Hugh A. ;
Niggemann, Bodo ;
Wahn, Ulrich ;
Beyer, Kirsten .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 126 (01) :83-91
[7]   Further fatalities caused by anaphylactic reactions to food, 2001-2006 [J].
Bock, S. Allan ;
Munoz-Furlong, Anne ;
Sampson, Hugh A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (04) :1016-1018
[8]   Fatalities due to anaphylactic reactions to foods [J].
Bock, SA ;
Muñoz-Furlong, A ;
Sampson, HA .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2001, 107 (01) :191-193
[9]  
Branum Amy M, 2008, NCHS Data Brief, P1
[10]   Successful oral tolerance induction in severe peanut allergy [J].
Clark, A. T. ;
Islam, S. ;
King, Y. ;
Deighton, J. ;
Anagnostou, K. ;
Ewan, P. W. .
ALLERGY, 2009, 64 (08) :1218-1220