由于 IL10、IL10 受体 alpha 或 beta 基因突变导致的极早发性 IBD 的表型特征： Genius 工作组的一项调查。

Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group.

机构信息

*Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France; †Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France; ‡Department of Pediatric Gastroenterology, ErasmusMC-Sophia Children's Hospital, Rotterdam, the Netherlands; §Department of Gastroenterology, Great Ormond Street Hospital for Sick Children and Institute of Child Health, London, United Kingdom; ‖Pediatric Gastroenterology Unit, Centro Hospitalar do Porto, Porto, Portugal; ¶Marienhospital, Bonn, Germany; **Department of Gastroenterology, Hepatology and Feeding Disorders, The Children's Memorial Health Institute, Warsaw, Poland; ††Gastroenterologia, Endoscopia Digestiva, Epatologia e Cura del Bambino con Trapianto di Fegato, Dipartimento Salute della Donna e del Bambino, Padova, Italy; ‡‡Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service d'anatomopathologie, Paris, France; §§Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de radiologie, Paris, France; ‖‖INSERM U989, Paris, France; and ¶¶INSERM U768, Paris, France.

出版信息

Inflamm Bowel Dis. 2013 Dec;19(13):2820-8. doi: 10.1097/01.MIB.0000435439.22484.d3.

DOI:10.1097/01.MIB.0000435439.22484.d3

PMID:24216686

Abstract

OBJECTIVE

Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution.

DESIGN

Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic-histological, immunobiological, and radiological findings. Functional assays to confirm defective responses to IL10 were performed on peripheral blood mononuclear cells.

RESULTS

A functional defect in IL10 signaling was confirmed in all IL10R patients tested. Disease started with severe diarrhea within the first 12 weeks in all patients. All infants showed Crohn's disease-like ulcerations limited to the colon with marked perianal inflammation (fissures, abscess, and fistula); disease progression to the small bowel occurred in only 1 patient. Four of the 10 patients had granulomata on histology, and all patients showed Crohn's disease-like mesenteric infiltration on imaging. Disease pattern was indistinguishable between IL10R alpha or beta chain or IL10 defects; autoimmunity was not observed. Mutations in IL10 were more frequently associated with bacterial and viral infections. Patients responded partially to treatment with steroids or anti-tumor necrosis factor drugs, whereas hematopoietic stem cell transplantation proved efficacious.

CONCLUSION

The importance of the IL10 pathway within the colonic mucosa is highlighted by the development of severe colitis within a few weeks in infants with mutations in IL10, IL10RA, or IL10RB. Immunosuppression failed to correct the defect in this pathway, which seems to be a key to controlling inflammation in the colon.

摘要

目的

发病于生命最初几个月的早发性炎症性肠病可能与特定的遗传缺陷有关。我们建立了 GENetically determined ImmUne-mediated enteropathieS（GENIUS）网络，并收集了 IL10 轴有明确缺陷的婴儿，以准确表型分析疾病的表现和演变。

设计

对 10 名 IL10、IL10RA 或 IL10RB 基因突变导致的早发性炎症性肠病患者的临床、内镜-组织学、免疫生物学和影像学表现进行了特征描述。对外周血单个核细胞进行了确认 IL10 反应缺陷的功能检测。

结果

所有接受检测的 IL10R 患者均证实存在 IL10 信号传导功能缺陷。所有患者均在出生后 12 周内出现严重腹泻。所有婴儿均表现为局限于结肠的克罗恩病样溃疡，伴有明显肛周炎症（裂隙、脓肿和瘘管）；仅 1 例患者疾病进展至小肠。10 例患者中有 4 例组织学上有肉芽肿，所有患者影像学上均有克罗恩病样肠系膜浸润。IL10Rα或β链或 IL10 缺陷的疾病模式无明显差异；未观察到自身免疫。IL10 突变与细菌和病毒感染的关系更为密切。患者对皮质类固醇或抗肿瘤坏死因子药物治疗有部分反应，而造血干细胞移植证明有效。