Lewis Kimberly, Butts Ryan, Antonio Quiros J, Hudspeth Michelle, Twombley Katherine, Savage Andrew, Self Sally, Burnette Ali, Sun Shaoli
Medical University of South Carolina - MUSC, Charleston, SC, USA.
Department of Pediatrics Cardiology, MUSC, Charleston, SC, USA.
Pediatr Transplant. 2017 Mar;21(2). doi: 10.1111/petr.12877. Epub 2017 Jan 17.
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis. Transition from tacrolimus to sirolimus successfully increased T regulatory cells and resolved enteritis and hepatitis symptoms. Data support that thymectomy at <1 year of age increases risk of autoimmune disease due to abnormal immune maturation. Studies suggest that the sirolimus promotes the upregulation of the FoxP3 protein that is classically associated with Tregs. In turn, Tregs prevent the maturation of autoreactive B cells that lead to autoimmune reactions.
自身免疫性肠病(AIE)是儿童罕见疾病,表现为严重腹泻和吸收不良,由免疫介导的肠黏膜损伤引起。AIE常与包括IPEX综合征(免疫失调、多内分泌病和肠病,X连锁)在内的各种免疫缺陷综合征相关。功能失调的调节性T细胞是IPEX综合征和AIE发病机制的根源,因为它们对于维持对自身抗原的耐受性和清除自身反应性B细胞至关重要。本病例报告描述了一名10岁接受心脏移植和全胸腺切除术的患者,长期使用他克莫司进行免疫抑制,出现了AIE和周期性肝炎的肠外表现。从他克莫司转换为西罗莫司成功增加了调节性T细胞数量,并缓解了肠炎和肝炎症状。数据支持1岁前进行胸腺切除术会因免疫成熟异常而增加自身免疫性疾病的风险。研究表明,西罗莫司可促进与调节性T细胞经典相关的FoxP3蛋白上调。反过来,调节性T细胞可阻止导致自身免疫反应的自身反应性B细胞成熟。