Stockfelt Marit, Hong Mun-Gwan, Hesselmar Bill, Adlerberth Ingegerd, Wold Agnes E, Schwenk Jochen M, Lundell Anna-Carin, Rudin Anna
Institute of Medicine, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30, Göteborg, Sweden.
Affinity Proteomics, SciLifeLab, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
Clin Proteomics. 2021 Mar 15;18(1):11. doi: 10.1186/s12014-021-09318-w.
Protein profiles that can predict allergy development in children are lacking and the ideal sampling age is unknown. By applying an exploratory proteomics approach in the prospective FARMFLORA birth cohort, we sought to identify previously unknown circulating proteins in early life that associate to protection or risk for development of allergy up to 8 years of age.
We analyzed plasma prepared from umbilical cord blood (n = 38) and blood collected at 1 month (n = 42), 4 months (n = 39), 18 months (n = 42), 36 months (n = 42) and 8 years (n = 44) of age. We profiled 230 proteins with a multiplexed assay and evaluated the global structure of the data with principal component analysis (PCA). Protein profiles informative to allergic disease at 18 months, 36 months and/or 8 years were evaluated using Lasso logistic regression and random forest.
Two clusters emerged in the PCA analysis that separated samples obtained at birth and at 1 month of age from samples obtained later. Differences between the clusters were mostly driven by abundant plasma proteins. For the prediction of allergy, both Lasso logistic regression and random forest were most informative with samples collected at 1 month of age. A Lasso model with 27 proteins together with farm environment differentiated children who remained healthy from those developing allergy. This protein panel was primarily composed of antigen-presenting MHC class I molecules, interleukins and chemokines.
Sampled at one month of age, circulating proteins that reflect processes of the immune system may predict the development of allergic disease later in childhood.
目前缺乏能够预测儿童过敏症发展的蛋白质谱,且理想的采样年龄尚不清楚。通过在前瞻性FARMFLORA出生队列中应用探索性蛋白质组学方法,我们试图识别生命早期未知的循环蛋白,这些蛋白与8岁前过敏症发展的保护因素或风险因素相关。
我们分析了从脐带血(n = 38)以及1个月(n = 42)、4个月(n = 39)、18个月(n = 42)、36个月(n = 42)和8岁(n = 44)时采集的血液中制备的血浆。我们使用多重检测方法对230种蛋白质进行了分析,并通过主成分分析(PCA)评估了数据的整体结构。使用套索逻辑回归和随机森林评估了在18个月、36个月和/或8岁时对过敏性疾病有信息价值的蛋白质谱。
PCA分析中出现了两个聚类,将出生时和1个月大时采集的样本与之后采集的样本分开。聚类之间的差异主要由丰富的血浆蛋白驱动。对于过敏症的预测,套索逻辑回归和随机森林在1个月大时采集的样本中信息含量最高。一个包含27种蛋白质的套索模型与农场环境一起区分了保持健康的儿童和患过敏症的儿童。这个蛋白质组主要由抗原呈递的MHC I类分子、白细胞介素和趋化因子组成。
在1个月大时采样,反映免疫系统过程的循环蛋白可能预测儿童后期过敏性疾病的发展。