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,危及生命的婴儿发作性结肠炎。我们试图基于大量已证实的IL10信号缺陷的患者来准确地表现这种疾病,并阐明异基因造血干细胞移植(HSCT)的作用。
我们分析了61例患者的表型,并回顾了78例以前报道的其他病例,这些病例在编码IL10或IL10R的基因中发现了突变。我们还比较了白细胞介素10受体B(IL10RB)患者的临床特征,白细胞介素-10受体A(IL10RA),和IL10突变。评估同种异体HSCT的治疗效果。
我们发现疾病发病时间非常早:70.3%在出生后30天内,94.9%在出生后的头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(33.8%和51.8%,分别)。发病时间差异无统计学意义,肛周病变受累,或IL10RB患者的死亡率,IL10RA,或IL10缺乏。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缺乏症相比,更高的百分比(32%,28例患者中有9例具有IL10RB突变的患者发展为B细胞淋巴瘤(P<0.01)。与其他地区相比,在东亚国家的患者中检测到更高的IL10RA突变百分比(98.7%)(P<0.01),具有c.C301T和c.G537A的热点突变位点。同种异体造血干细胞移植是有效的,但死亡率很高(17.5%,7of40)。
我们的研究扩展了目前关于具有IL10信号缺陷的基因型相关表型的知识。在具有IL10RB突变的患者中,B细胞淋巴瘤的频率高于预期。与其他人群相比,东亚可能有独特的遗传结构。尽管同种异体HSCT代表了IL10和IL10R缺陷患者的因果治疗方法,一句谨慎的话是有道理的。
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.