Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK

Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK
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DOI:
10.1111/all.12482
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发表时间:
2014-10-01
期刊:
影响因子:
12.4
通讯作者:
Hoffmann, H. J. H.
Hoffmann, H. J. H.
中科院分区:
医学1区
文献类型:
--
作者:
Christensen, S. K. Witting;Krohn, I. Kortekaas;Hoffmann, H. J. H.

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研究背景序贯变应原脱敏治疗可使过敏患者获得暂时的耐受。我们适应了一个临床协议,脱敏人血嗜碱性粒细胞体外和研究的机制和过敏原specificity.MethodsWe包括28名成人,草过敏的科目。通过在嗜碱性粒细胞活化试验中用8个对数稀释的草变应原测量活化的CD 63(+)CD 193(+)SS(低)嗜碱性粒细胞来确定最佳活化变应原浓度。全血中的嗜碱性粒细胞通过以1:1000的最佳剂量开始的10个步骤与2倍至2.5倍增加的过敏原剂量孵育而脱敏。在变应原刺激3 min后评估p38丝裂原活化蛋白激酶(MAPK)的参与(n=7)。通过用草过敏原使来自多过敏受试者的细胞脱敏并用最佳剂量的草、桦树、结果脱敏治疗使最佳变应原剂量激发的血液嗜碱性粒细胞应答率从中位值(IQR)的81.0%下降到最佳变应原剂量激发的81.0%,(66.3-88.8)~ 35.4%(19.8-47.1,P
BackgroundSequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.MethodsWe included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+)SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3min of allergen stimulation (n=7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n=10).ResultsDesensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P