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中国循证儿科杂志

中国循证儿科杂志 ›› 2016, Vol. 11 ›› Issue (3): 171-176.

• 论著 • 上一篇    下一篇

脐血干细胞移植治疗白介素10受体A基因突变导致的极早发型炎症性肠病1例病例报告并文献复习

彭凯玥1,4，钱晓文2,4，吴冰冰3，黄志恒1，芦军萍1，翟晓文2，王慧君3，郑翠芳1，黄瑛1   

  1. 复旦大学附属儿科医院 1 消化科，2 血液科，3 分子诊断中心上海，201102；4 共同第一作者
  • 收稿日期:2016-06-25 修回日期:2016-06-25 出版日期:2016-06-25 发布日期:2016-06-25
  • 通讯作者: 黄瑛

Umbilical cord blood stem cell transplantation treatment for very early onset inflammatory bowel disease due to IL-10RA mutation: A case report and literature review

PENG Kai-yue1,4, QIAN Xiao-wen2,4, WU Bin-bin3, HUANG Zhi-heng1, LU Jun-ping1, ZHAI Xiao-wen2, WANG Hui-jun3, ZHENG Cui-fang1, HUANG Ying1   

  1. 1 Department of Gastroenterology, 2 Department of Hematology, 3 Molecular Diagnostic Center, Children′s Hospital, Fudan University, Shanghai 201102, China；4 Co-first author
  • Received:2016-06-25 Revised:2016-06-25 Online:2016-06-25 Published:2016-06-25
  • Contact: HUANG Ying

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1984

被引次数

6

摘要：

目的通过IL-10RA基因突变导致的炎症性肠病 (IBD)病例，进一步深化认识极早发型IBD (VEO-IBD)的特点。方法 报告1例VEO-IBD临床诊断（症状、体征和肠镜），全外显子组测序（WES）明确病因，脐血干细胞移植精准治疗的过程。结果患儿，女，44 d，足月，生后8 d始腹泻呈进行性加重（多至每天10~20次），持续间断发热，重度营养不良。患儿姐姐1月龄反复发热、腹泻和鹅口疮，5月龄时疑尿道瘘不治死亡。入复旦大学附属儿科医院4 d外阴皮肤红肿，渐形成肛瘘，体重2.6 kg。肠镜示直肠黏膜增生性病变，乙状结肠、降结肠可见纵行溃疡和鹅卵石样增生。予抗感染、沙利度胺6 mg·d-1和美沙拉秦150 mg·d-1控制肠道炎症反应，肠道内外营养支持等对症治疗。行WES明确为IL-10RA基因缺陷，获得同性别无关供者HLA基因位点8/10的脐血行干细胞移植。移植后12周嵌合体率95.7%，Sanger测序及蛋白功能验证IL-10RA基因突变点被修复，IL-10信号通路轴功能恢复正常。患儿大便逐渐成型，体重5.2 kg，结肠镜显示肠黏膜愈合，仅见少量增生和疤痕，移植后10个月大便钙卫蛋白72 μg·g-1。结论脐血干细胞移植作为治疗IL-10RA基因突变导致的VEO-IBD方法，值得积累更多的病例。

Abstract:

ObjectiveTo deepen the understanding of the characteristics of very early onset inflammatory bowel disease (VEO-IBD) , an infant diagnosed as VEO-IBD due to IL-10RA mutation was reported. MethodsAn infant was dianosed as VEO-IBD based on her clinical manifestations and colonoscopy character. The whole exome sequencing (WES) was performed to confirm the gene deficiency, and the patient was treated by umbilical cord blood stem cell transplantation (UCBT).ResultsA 44-day-old, full-term, female infant remained healthy until developing diarrhea(up to 10 to 20 times per day) on postnatal day 8 with recurrent fever and severe malnutrition. The patient's older sister presented the similar manifestations (recurrent fever, diarrhea and thrush) at one month after birth and died of suspected urethral fistula at the age of 5 months. The patient displayed the perianal abscess which progressed to a fistula with the body weight going down to 2.6 kg 4 days after admission to Children's Hospital of Fudan University. Colonoscopy showed hyperplastic lesions in rectum, straight ulcerations and cobblestone-like appearance in sigmoid colon and descending colon. Thalidomide 6 mg, qd and mesalazine 150mg, qd were used to control intestinal inflammation with enteral and parenteral nutrition support. IL-10RA gene deficiency was confirmed by Sanger sequencing, and umbilical cord blood stem cell transplantation was performed. The stem cells were obtained from an unrelated sex-matched and 8/10 HLA allele-matched UCB. Chimerism was 95.7% 12 weeks after transplantation. IL-10RA gene deficiency and malfunction returning to normal were confirmed by Sanger sequencing and western blotting. The patient's formed stool appeared gradually with the body weigh increasing to 5.2 kg. Colonoscopy showed mucosal healing. At 10 months after transplantation, stool calprotectin was normal (72 μg·g-1).ConclusionThe umbilical cord blood stem cell transplantation is a promising treatment for VEO-IBD due to IL-10RA mutation. It is worth to gather more experiences.