Assessment of systemic genetic damage in pediatric inflammatory bowel disease
| Autor: | David P. Lovell, Lawrence J. Saubermann, Ayesha Baig, Jeffrey C. Bemis, James T. MacGregor, Svetlana L. Avlasevich, Dorothea K. Torous, Stephen D. Dertinger |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Constipation Reticulocytes Adolescent Epidemiology Health Toxicology and Mutagenesis CD59 Antigens Disease 010501 environmental sciences medicine.disease_cause 01 natural sciences Inflammatory bowel disease Gastroenterology Article New onset 03 medical and health sciences Young Adult Antigens CD Internal medicine medicine Humans Child Genetics (clinical) Irritable bowel syndrome Micronuclei Chromosome-Defective 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Mutation Micronucleus Tests business.industry Membrane Proteins medicine.disease Control subjects Inflammatory Bowel Diseases Etiology Female medicine.symptom business Cell Adhesion Molecules |
| Zdroj: | Environ Mol Mutagen |
| ISSN: | 1098-2280 |
| Popis: | 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 ± std. dev. = 3.1 ± 2.3 x 10-6 versus 3.6 ± 5.6 x 10-6 , respectively). In contrast, of 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 = 0.049). 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 = 0.040). 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. |
| Databáze: | OpenAIRE |
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