Assessment of systemic genetic damage in pediatric inflammatory bowel disease.
Assessment of systemic genetic damage in pediatric inflammatory bowel disease.
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DOI：
10.1002/em.22403
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发表时间：
2020-11
影响因子：
2.8
通讯作者：
Dertinger SD
中科院分区：
文献类型：
--
作者：
Baig A;Avlasevich SL;Torous DK;Bemis JC;Saubermann LJ;Lovell DP;MacGregor JT;Dertinger SD
炎症性肠病（IBD）远端部位癌症的病因学尚未完全了解，需要进一步研究。我们通过测量突变表型（CD 59 −/CD 55 −）网织红细胞（MUT RET）的频率作为PIG-A突变的报告基因，以及微核网织红细胞（MN-RET）的频率作为染色体损伤的指标，研究了儿童IBD患者的血细胞是否表现出基因组损伤水平升高。将IBD患者（n = 18例新发疾病，46例确诊疾病）与年龄匹配的对照组（来自同一诊所的便秘或肠易激综合征患者，n = 30）和19-24岁的年轻健康成人（n = 25）进行比较。IBD患者未显示MUT RET相对于对照组升高的迹象（平均值± SD分别为3.1 ± 2.3 × 10−6 vs. 3.6 ± 5.6 × 10−6）。相比之下，获得%MN-RET测量值的59名IBD患者中，10名超过了来自对照受试者的上限90%容许区间（即，0.42%）。此外，10例MN-RET升高的IBD患者均已确诊疾病（10/42），无新发（0/17）（p = 0.049）。有趣的是，在采集血液时，染色体损伤增加的每例受试者均接受基于抗TNF的单药治疗（10/10，100%），而这种治疗在MN-RET ≤0.42%的患者中不太常见（20/32，63%）（p = 0.040）。结果清楚地表明，需要进一步的工作，以了解本文提供的结果是否是可重复的，如果是，以阐明在一些IBD患者中引起MN-RET频率升高的致病因素。
The etiology of distal site cancers in inflammatory bowel disease (IBD) is not well understood and requires further study. We investigated whether pediatric IBD patients' blood cells exhibit elevated levels of genomic damage by measuring the frequency of mutant phenotype (CD59−/CD55−) reticulocytes (MUT RET) as a reporter of PIG-A mutation, and the frequency of micronucleated reticulocytes (MN-RET) as an indicator of chromosomal damage. IBD patients (n = 18 new-onset disease, 46 established disease) were compared to age-matched controls (constipation or irritable bowel syndrome patients from the same clinic, n = 30) and young healthy adults age 19–24 (n = 25). IBD patients showed no indication of elevated MUT RET relative to controls (mean ± SD = 3.1 ± 2.3 × 10−6 vs. 3.6 ± 5.6 x 10−6, respectively). In contrast, 59 IBD patients where %MN-RET measurements were obtained, 10 exceeded the upper bound 90% tolerance interval derived from control subjects (i.e., 0.42%). Furthermore, each of the 10 IBD patients with elevated MN-RET had established disease (10/42), none were new-onset (0/17) (p = .049). Interestingly, each of the subjects with increased chromosomal damage was receiving anti-TNF based monotherapy at the time blood was collected (10/10, 100%), whereas this therapy was less common (20/32, 63%) among patients that exhibited ≤0.42% MN-RET (p = .040). The results clearly indicate the need for further work to understand whether the results presented herein are reproducible and if so, to elucidate the causative factor(s) responsible for elevated MN-RET frequencies in some IBD patients.
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DOI：
10.1016/0165-1161(93)90140-u
发表时间：
1993-10-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
TOMETSKO, AM;TOROUS, DK;DERTINGER, SD
通讯作者：
DERTINGER, SD
影响因子：
20.3
作者：
WARE, RE;ROSSE, WF;HALL, SE
通讯作者：
HALL, SE
影响因子：
29.4
作者：
Khan, Nabeel;Abbas, Ali M.;Bazzano, Lydia A.
通讯作者：
Bazzano, Lydia A.
DOI：
10.2147/phmt.s64943
发表时间：
2015
期刊：
Pediatric health, medicine and therapeutics
影响因子：
--
作者：
Kierkus J;Szymanska E;Oracz G;Wiernicka A;Dadalski M
通讯作者：
Dadalski M
影响因子：
2.8
作者：
Torous DK;Avlasevich SL;Khattab MG;Baig A;Saubermann LJ;Chen Y;Bemis JC;Lovell DP;Walker VE;MacGregor JT;Dertinger SD
通讯作者：
Dertinger SD