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首页> 外文期刊>Allergy >Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK
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Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK

机译：嗜碱性粒细胞的顺序过敏原脱敏是非特异性的，可能涉及p38 MAPK

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Background: Sequential 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.Methods: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63+ CD193+SSLow 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 3 min 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).Results: Desensitization 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 < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05).Conclusion: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation.
机译：背景：顺序过敏原脱敏为过敏患者提供了暂时的耐受性。我们采用临床方案对离体血液嗜碱性粒细胞进行脱敏，并研究了其机理和过敏原特异性。方法：我们纳入了28名成人，草类过敏性受试者。最佳的活化变应原浓度是通过在8种对数稀释度的草变应原的嗜碱性粒细胞活化试验中测量活化的CD63 + CD193 + SSLow嗜碱粒细胞来确定的。通过从最佳剂量的1：1000开始的10步中，以两倍至2.5倍的变应原剂量孵育，使全血中的嗜碱性粒细胞脱敏。在过敏原刺激3分钟后评估了p38丝裂原活化蛋白激酶（MAPK）的参与（n = 7）。通过用草过敏原对多变态反应对象的细胞脱敏，并以最适剂量的草，桦木，重组室内尘螨（rDer p2）过敏原或抗IgE（n = 10）进行挑战，研究了过敏原的特异性。结果：脱敏降低了分数最佳反应原剂量的嗜血性嗜碱性粒细胞从中位（IQR）从81.0％（66.3-88.8）增至35.4％（19.8-47.1，P <0.0001）。 CD63 MFI表达从68 248（29 336-92 001）降低至30 496（14 046-46 179，P <0.0001）。来自多变态反应受试者的嗜碱性粒细胞用草变应原脱敏。用草过敏原激发可激活39.6％（15.8-58.3）。无关的攻击（桦木，rDer p2或抗IgE）导致53.4％的激活（30.8-66.8，与草相比，P = 0.16）。脱敏作用将p38 MAPK磷酸化从中值48.1％（15.6-92.8）降至26.1％（7.4-71.2，P = 0.047），并与CD63上调的减少相关（n = 7，r> 0.79，P <0.05）。脱敏在p38 MAPK磷酸化之前的阶段迅速且非特异性地减弱了嗜碱性粒细胞的应答。

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