Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Sci Rep. 2017 Dec 15;7(1):17687. doi: 10.1038/s41598-017-17798-w.
Food allergy is immediate hypersensitive reactions to ingested foods. Since early diagnosis is effective for disease control, development of an objective diagnostic index is required. Using mediator-lipidomics, we found that levels of the urinary prostaglandin D (PGD) metabolite, tetranor-PGDM, reflected the severity of the allergic symptoms and intestinal mast cell hyperplasia in mice. Repeated oral challenges with ovalbumin promoted allergic symptoms in sensitized mice. Particularly, the allergic mice presented with increased numbers of intestinal mast cells, which strongly expressed hematopoietic PGD synthase (H-PGDS). The levels of urinary tetranor-PGDM increased as the disease progressed. Treatment with a mast cell inactivator or an anti-inflammatory steroid attenuated these symptoms and decreased the tetranor-PGDM urinary levels. The levels of urinary tetranor-PGDM did not correlate with the disease severity in murine models of colitis, asthma, or allergic dermatitis. Furthermore, we have shown that urinary levels of tetranor-PGDM were significantly higher in patients with food allergy than those in healthy volunteers and patients with other types of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. These findings suggest that urinary tetranor-PGDM is a useful diagnostic index of food allergy in both mice and humans.
食物过敏是对摄入食物的即刻超敏反应。由于早期诊断对疾病控制有效,因此需要开发客观的诊断指标。使用介质脂质组学,我们发现尿前列腺素 D(PGD)代谢物四氢基-PGDM 的水平反映了小鼠过敏症状和肠道肥大细胞增生的严重程度。用卵清蛋白反复口服挑战可促进致敏小鼠发生过敏症状。特别是,过敏小鼠的肠道肥大细胞数量增加,这些细胞强烈表达造血 PGD 合酶(H-PGDS)。随着疾病的进展,尿中四氢基-PGDM 的水平增加。用肥大细胞失活剂或抗炎类固醇治疗可减轻这些症状并降低尿中四氢基-PGDM 的水平。尿中四氢基-PGDM 的水平与结肠炎、哮喘或过敏性皮炎等其他类型过敏疾病的小鼠模型中的疾病严重程度无关。此外,我们已经表明,与健康志愿者和哮喘、过敏性鼻炎和特应性皮炎等其他类型过敏疾病的患者相比,食物过敏患者的尿中四氢基-PGDM 水平明显更高。这些发现表明,尿中四氢基-PGDM 是一种在小鼠和人类中均有用的食物过敏诊断指标。