Sex Differences in Blood Transcriptional Profiles and Clinical Phenotypes in Pediatric Patients with Eosinophilic Esophagitis
Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized, chronic inflammatory disease. Recent reports suggest clinical differences between males and females.
OBJECTIVE: To define the relevant molecular pathways that could be related to clinical phenotypes in children with EoE.
METHODS: We performed blood RNA expression analysis in children with newly diagnosed EoE and matched, healthy controls, and applied bioinformatics tools to define EoE host immune biosignatures. Questionnaires and medical records were used to characterize symptoms, esophagogastroduodenoscopy results, and treatment response.
RESULTS: Forty-one subjects (aged 2-17 years) were enrolled; the cohort consisted of 27 males and 14 females. Patients were randomly divided into a discovery cohort (21 EoE patients and 12 controls) that identified 544 significant differentially expressed transcripts (P ≤ .01; 1.25-fold change). Those 544 transcripts correctly classified most EoE patients in the validation cohort (n = 20) from healthy controls. Global transcriptional perturbation relative to healthy controls, Molecular Distance to Health scores were greater in EoE patients than controls (P = .003). When we analyzed subjects based on age and sex, males 13 years of age and older were more likely to have food impactions (P = .033) and to have higher endoscopic severity scores (P = .036). Separate group comparisons according to sex identified 294 differentially expressed transcripts in males and 643 transcripts in female EoE patients. Of those, 37 genes were shared and similarly expressed irrespective of sex.
CONCLUSIONS: Whole blood transcriptional analysis represents a promising noninvasive tool to assess activity of the immune/inflammatory response in children with EoE. Male and female EoE patients showed robust differences in gene expression suggesting distinct pathogenic endotypes.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
The journal of allergy and clinical immunology. In practice - 9(2021), 9 vom: 06. Sept., Seite 3350-3358.e8 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Erwin, Elizabeth A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.10.2021 Date Revised 27.10.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jaip.2021.06.043 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM328109363 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM328109363 | ||
| 003 | DE-627 | ||
| 005 | 20231225202243.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jaip.2021.06.043 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1093.xml |
| 035 | |a (DE-627)NLM328109363 | ||
| 035 | |a (NLM)34265446 | ||
| 035 | |a (PII)S2213-2198(21)00774-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Erwin, Elizabeth A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sex Differences in Blood Transcriptional Profiles and Clinical Phenotypes in Pediatric Patients with Eosinophilic Esophagitis |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.10.2021 | ||
| 500 | |a Date Revised 27.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized, chronic inflammatory disease. Recent reports suggest clinical differences between males and females | ||
| 520 | |a OBJECTIVE: To define the relevant molecular pathways that could be related to clinical phenotypes in children with EoE | ||
| 520 | |a METHODS: We performed blood RNA expression analysis in children with newly diagnosed EoE and matched, healthy controls, and applied bioinformatics tools to define EoE host immune biosignatures. Questionnaires and medical records were used to characterize symptoms, esophagogastroduodenoscopy results, and treatment response | ||
| 520 | |a RESULTS: Forty-one subjects (aged 2-17 years) were enrolled; the cohort consisted of 27 males and 14 females. Patients were randomly divided into a discovery cohort (21 EoE patients and 12 controls) that identified 544 significant differentially expressed transcripts (P ≤ .01; 1.25-fold change). Those 544 transcripts correctly classified most EoE patients in the validation cohort (n = 20) from healthy controls. Global transcriptional perturbation relative to healthy controls, Molecular Distance to Health scores were greater in EoE patients than controls (P = .003). When we analyzed subjects based on age and sex, males 13 years of age and older were more likely to have food impactions (P = .033) and to have higher endoscopic severity scores (P = .036). Separate group comparisons according to sex identified 294 differentially expressed transcripts in males and 643 transcripts in female EoE patients. Of those, 37 genes were shared and similarly expressed irrespective of sex | ||
| 520 | |a CONCLUSIONS: Whole blood transcriptional analysis represents a promising noninvasive tool to assess activity of the immune/inflammatory response in children with EoE. Male and female EoE patients showed robust differences in gene expression suggesting distinct pathogenic endotypes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Eosinophilic esophagitis | |
| 650 | 4 | |a Pediatrics | |
| 650 | 4 | |a Phenotypes | |
| 650 | 4 | |a Sex differences | |
| 650 | 4 | |a Transcriptional analysis | |
| 700 | 1 | |a Jaramillo, Lisa M |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Bennett |e verfasserin |4 aut | |
| 700 | 1 | |a Kruszewski, Patrice G |e verfasserin |4 aut | |
| 700 | 1 | |a Kahwash, Basil |e verfasserin |4 aut | |
| 700 | 1 | |a Grayson, Mitchell H |e verfasserin |4 aut | |
| 700 | 1 | |a Mejias, Asuncion |e verfasserin |4 aut | |
| 700 | 1 | |a Ramilo, Octavio |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of allergy and clinical immunology. In practice |d 2013 |g 9(2021), 9 vom: 06. Sept., Seite 3350-3358.e8 |w (DE-627)NLM227247523 |x 2213-2201 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2021 |g number:9 |g day:06 |g month:09 |g pages:3350-3358.e8 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jaip.2021.06.043 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2021 |e 9 |b 06 |c 09 |h 3350-3358.e8 | ||