Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China.
Department of Hematology & Oncology, Children's Hospital of Fudan University, Shanghai, China.
Inflamm Bowel Dis. 2019 Mar 14;25(4):756-766. doi: 10.1093/ibd/izy289.
Interleukin-10 (IL10)/interleukin-10 receptor (IL10R) deficiency is a rare disease with life-threatening infantile-onset colitis. We sought to accurately phenotype this disorder based on a large cohort of patients with a proven defect of IL10 signaling and to clarify the effects of allogeneic hematopoietic stem cell transplantation (HSCT).
We analyzed the phenotypes of our 61 patients and reviewed 78 other previously reported cases with identified mutations in the genes encoding IL10 or IL10R. We also compared the clinical features of patients with interleukin-10 receptor B (IL10RB), interleukin-10 receptor A (IL10RA), and IL10 mutations. The therapeutic effects of allogeneic HSCT were evaluated.
We found that the disease onset time was extremely early: 70.3% within 30 days postnatal and 94.9% within the first 6 months of life. In addition, 94.2% of patients typically presented with perianal lesions. Oral ulcers and skin rash were common extra-intestinal manifestations (33.8% and 51.8%, respectively). There was no statistically significant difference in disease onset time, perianal lesion involvement, or mortality rate among patients with IL10RB, IL10RA, or IL10 deficiency. However, the surgery rate was higher in patients with IL10RB mutations than in those with IL10 or IL10RA mutations (P < 0.05). Compared with those with IL10RA deficiency, a higher percentage (32%, 9 of 28) of patients with IL10RB mutations developed B-cell lymphoma (P < 0.01). Compared with other regions, a higher percentage (98.7%) of IL10RA mutations was detected among patients in East Asia countries (P < 0.01), with hot-spot mutation sites of c.C301T and c.G537A. Allogeneic HSCT is efficacious but has a high mortality rate (17.5%, 7 of 40).
Our study expands the current knowledge on the genotype-correlated phenotypes with a defect of IL10 signaling. B-cell lymphoma was more frequent than would be expected in patients with IL10RB mutations. There may be a unique genetic architecture among Eastern Asia compared with other populations. Although allogeneic HSCT represents a causal therapeutic approach for IL10-and IL10R-deficient patients, a word of caution is warranted.
白细胞介素-10（IL10）/白细胞介素-10 受体（IL10R）缺乏症是一种罕见的疾病，具有危及生命的婴儿期发作性结肠炎。我们试图根据一大群具有 IL10 信号缺陷的患者，并阐明同种异体造血干细胞移植（HSCT）的效果，准确表型这种疾病。
我们分析了 61 名患者的表型，并回顾了 78 例其他先前报道的具有 IL10 或 IL10R 编码基因突变的病例。我们还比较了白细胞介素-10 受体 B（IL10RB）、白细胞介素-10 受体 A（IL10RA）和 IL10 突变患者的临床特征。评估了同种异体 HSCT 的治疗效果。
我们发现疾病发病时间极早：70.3%在出生后 30 天内，94.9%在生命的前 6 个月内。此外，94.2%的患者通常表现为肛周病变。口腔溃疡和皮疹是常见的肠外表现（分别为 33.8%和 51.8%）。IL10RB、IL10RA 或 IL10 缺乏症患者的发病时间、肛周病变受累或死亡率无统计学差异。然而，IL10RB 突变患者的手术率高于 IL10 或 IL10RA 突变患者（P<0.05）。与 IL10RA 缺乏症患者相比，IL10RB 突变患者中发生 B 细胞淋巴瘤的比例更高（32%，28 例中有 9 例，P<0.01）。与其他地区相比，东亚国家 IL10RA 突变患者的比例（98.7%，P<0.01）更高，热点突变位点为 c.C301T 和 c.G537A。同种异体 HSCT 有效，但死亡率较高（17.5%，40 例中有 7 例）。
本研究扩展了当前关于 IL10 信号缺陷相关表型的基因型相关性知识。与预期相比，IL10RB 突变患者中 B 细胞淋巴瘤更为常见。与其他人群相比，东亚人群可能存在独特的遗传结构。虽然同种异体 HSCT 是 IL10 和 IL10R 缺乏症患者的因果治疗方法，但需要谨慎对待。
