Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Karolinska Institutet, Department of Clinical Science and Education, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
Pediatr Allergy Immunol. 2019 Aug;30(5):522-530. doi: 10.1111/pai.13047. Epub 2019 Apr 14.
Immunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy-related cytokine and chemokine levels, as well as IgA-responses upon a 3-year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis.
From children included in the GRAZAX Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3 years of treatment, and 2 years after treatment ending. By means of Luminex and ELISA methodologies, allergy-related cytokines and chemokines were measured in plasma samples and allergen-stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1-specific salivary IgA antibodies were performed using the same methods.
GRAZAX -treated children exhibited significantly higher levels of Phl p 1-specific salivary IgA and serum IgG , along with significantly lower skin prick test positivity, after 3 years of treatment and 2 years after treatment cessation. Additionally, plasma levels of the Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points. Timothy-induced ratios of IL-5/IL-13 over IFN-γ were significantly decreased after 3 years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters.
Phleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically-by increasing Th1-responses, decreasing Th2-responses, and inducing immunoregulatory responses-all signs of tolerance induction.
舌下免疫疗法对过敏儿童的全身和黏膜介质的免疫调节作用在很大程度上尚未得到探索。本研究的目的是研究过敏性儿童在接受 3 年的豚草花粉舌下免疫治疗后，与过敏相关的细胞因子和趋化因子水平以及 IgA 反应。
从参与 Grazax 哮喘预防研究的儿童中，在纳入时、治疗 3 年后和治疗结束后 2 年分析了血液和唾液样本。通过 Luminex 和 ELISA 方法，测量了血浆样本和过敏原刺激的外周血单个核细胞上清液中的与过敏相关的细胞因子和趋化因子。此外，使用相同的方法进行了总、分泌和 Phl p 1 特异性唾液 IgA 抗体的研究。
经过 3 年的治疗和治疗结束后 2 年，Grazax 治疗的儿童表现出明显更高水平的 Phl p 1 特异性唾液 IgA 和血清 IgG，以及明显更低的皮肤点刺试验阳性率。此外，在这些时间点，治疗组儿童的血浆中 Th1 相关趋化因子 CXCL10 和 CXCL11 的水平明显高于未治疗组。在有活性治疗的 3 年后，Timothy 诱导的 IL-5/IL-13 与 IFN-γ的比值显著降低，过敏鼻炎的症状无论是严重程度还是视觉模拟评分也都显著降低。然而，临床结果和免疫参数之间没有发现一致的相关性。
在花粉过敏的儿童中，Phleum pratense 舌下免疫疗法可以调节口腔黏膜和全身的免疫反应，通过增加 Th1 反应、减少 Th2 反应和诱导免疫调节反应，所有这些都是诱导耐受的迹象。
