Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.
目的： 探讨过敏原皮下特异性免疫治疗（subcutaneous immunotherapy，SCIT）在治疗早期对患者免疫指标和代谢水平的影响，深入了解SCIT治疗在调节免疫反应和代谢水平方面的作用，为进一步发现潜在生物标志物提供参考数据。 方法： 采用纵向研究方法，纳入2017年11月至2022年2月期间于广州医科大学附属第一医院儿科接受尘螨过敏原SCIT的受试者40例，其中单螨制剂治疗（single mite subcutaneous immunotherapy，SM-SCIT）和双螨制剂（double mite subcutaneous immunotherapy，DM-SCIT）治疗受试者各20例。本研究检测了受试者治疗前和治疗12个月后的尘螨过敏原特异性抗体和多元不饱和脂肪酸代谢水平，同时进行了肺功能检查，并通过症状视觉模拟量表（visual analogue scale，VAS）、哮喘控制测试问卷（asthma control test，ACT）和用药总评分（total medication scores，TMS）对患者的疗效进行随访，采用t检验、Mann-Whitney U检验等方法进行结果统计分析。 结果： 经SCIT治疗12个月后，两组的VAS总分（SM-SCIT：Z=-2.298，P<0.05；DM-SCIT：Z=-3.411，P<0.001）显著下降；ACT总分（SM-SCIT：Z=-2.054，P<0.05；DM-SCIT：Z=-2.014，P<0.05）和总用药评分（SM-SCIT：Z=-3.799，P<0.000 1；DM-SCIT：Z=-3.474，P<0.001）显著升高，此外，双螨治疗组MMEF75/25值显著升高（t=-2.253，P<0.05）。单螨治疗组的sIgE无明显变化（P>0.05），Der p、Der f、p 1、p 2、f 2和p 21组分sIgG4水平均显著升高（Z分别为-2.651、-3.771、-2.949、-2.912、-2.725、-2.128、-3.285，P均<0.05）；双螨治疗组的 Der p 2、f 2、p 7和p 23 组分sIgE（Z分别为-1.965、-2.028、-2.406、-2.134，P均<0.05）和Der p、Der f、p 1、p 2、f 1、f 2、p 10、p 21和p 23组分sIgG4水平均显著升高（Z分别为-3.808、-3.845、-3.061、-2.688、-2.464、-3.211、-2.371、-2.091、-2.427，P均<0.05）。代谢组学分析显示，在治疗初期，SM-SCIT治疗后花生四烯酸、二十二碳六烯酸、二十二碳五烯酸、二十碳五烯酸、5，9，12-十八碳三烯酸、5（S）-羟化二十烷四烯酸、二高-γ-亚麻酸显著升高（Z分别为-2.191、-2.497、-1.988、-2.090、-2.19、-2.803、-2.073，P均<0.05）；DM-SCIT组治疗后5（S）-羟化二十烷四烯酸显示升高，α-亚麻酸、二十碳二烯酸、二十碳一烯酸显著下降（Z分别-1.988、-2.090、-2.497、-1.988，P均<0.05）。相关性分析表明，花生四烯酸与尘螨特异性IgG4的变化呈显著负相关（r=-0.499，P<0.05），α-亚麻酸、5，9，12-十八碳三烯酸、二十碳五烯酸与尘螨der p 2的ΔsIgG4（r分别为0.451、0.420、0.474，P均<0.05）呈正相关。 结论： SCIT期间过敏原特异性抗体水平和多不饱和脂肪酸代谢水平发生显著变化，并且两者之间可能相互影响、相互作用。.