Division of Gastroenterology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA.
Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
Sci Adv. 2019 Aug 7;5(8):eaaw7756. doi: 10.1126/sciadv.aaw7756. eCollection 2019 Aug.
Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4 T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.
乳糜泻（CeD）是由对谷物麸质的免疫反应引起的，其治疗方法是采用无麸质饮食。在食用麸质后的数小时内，无论是经口摄入还是通过皮内注射摄入，接受治疗的患者都会出现胃肠道症状。为了测试麸质暴露是否会导致与症状相关的全身性细胞因子产生，在麸质挑战后对 CeD 患者进行了一系列多重细胞因子测量。肽注射至少升高了 15 种血浆细胞因子，其中 IL-2、IL-8 和 IL-10 最为突出（4 小时时的倍数增加分别为 272、11 和 1.2）。IL-2 和 IL-8 是仅在 2 小时升高的细胞因子，早于症状发作。在摄入麸质后，IL-2 是最早和最突出的细胞因子（4 小时时增加 15 倍）。这些观察结果得到了患者来源的麸质特异性 T 细胞克隆和原代淋巴细胞研究的支持，表明麸质特异性 CD4 T 细胞可能通过抗原暴露而被迅速重新激活，从而导致 CeD 相关的胃肠道症状。
