Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study.
Colitis
Eosinophil
Eosinophilic Colitis
Inflammatory Bowel Disease
Transcriptome
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
15
10
2021
revised:
09
01
2022
accepted:
11
01
2022
pubmed:
28
1
2022
medline:
27
4
2022
entrez:
27
1
2022
Statut:
ppublish
Résumé
Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.
Sections du résumé
BACKGROUND & AIMS
Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.
METHODS
Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived.
RESULTS
We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001).
CONCLUSIONS
We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.
Identifiants
pubmed: 35085569
pii: S0016-5085(22)00038-5
doi: 10.1053/j.gastro.2022.01.022
pmc: PMC9038694
mid: NIHMS1774352
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1635-1649Subventions
Organisme : NIAID NIH HHS
ID : K99 AI158660
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NCATS NIH HHS
ID : U2C TR002818
Pays : United States
Organisme : NIAID NIH HHS
ID : U54 AI117804
Pays : United States
Investigateurs
J Pablo Abonia
(J)
Seema Aceves
(S)
Samuel Almonte
(S)
Rachel Andrews
(R)
Sara Anvari
(S)
Ashley Arrington
(A)
Nicoleta Arva
(N)
Fred Atkins
(F)
Dominique Bailey
(D)
Alexis Berry
(A)
Bridget Besl
(B)
Scott Bolton
(S)
Peter Bonis
(P)
Wendy Book
(W)
Kimberly Bray
(K)
Teresa Brown
(T)
Cassandra Burger
(C)
Deirdre Burke
(D)
Jonathon Cahoon
(J)
Kelley Capocelli
(K)
Mirna Chehade
(M)
Eric Chiou
(E)
Margaret Collins
(M)
Carla Davis
(C)
Evan Dellon
(E)
Maureen DeMarshall
(M)
Lauren DiTommaso
(L)
Ranjan Dohil
(R)
Michael Eby
(M)
Gary Falk
(G)
David Fleischer
(D)
Heather Foote
(H)
Kelci Foss
(K)
Joel Friedlander
(J)
Patricia Fulkerson
(P)
Glenn Furuta
(G)
Debra Geno
(D)
Nirmala Gonsalves
(N)
Thomas Greuter
(T)
Sandeep Gupta
(S)
Frank Hamilton
(F)
Kirk Harris
(K)
Jennifer Harris
(J)
Ikuo Hirano
(I)
Girish Hiremath
(G)
Nicole Holland-Thomas
(N)
Lea Jacinto
(L)
Amir Kagalwalla
(A)
Timothy Kaseta
(T)
David Katzka
(D)
Kaitlin Keeley
(K)
Emad Khosh-Hemmat
(E)
Paneez Khoury
(P)
Eileen King
(E)
Kara Kliewer
(K)
Amy Klion
(A)
Jennifer Knowles
(J)
Kendra Kocher
(K)
Ellyn Kodroff
(E)
Jeffrey Krischer
(J)
Shay Kyle
(S)
John Leung
(J)
Meredith Levy
(M)
Chris Liacouras
(C)
Denise Mack
(D)
Lisa Martin
(L)
Ellen Martin
(E)
Talaya McCright-Gill
(T)
Paul Menard-Katcher
(P)
Calies Menard-Katcher
(C)
Gabriela Mendoza
(G)
Melissa Mingler
(M)
Mike Minnicozzi
(M)
Amanda Muir
(A)
Vincent Mukkada
(V)
Cristin Murray-Petzold
(C)
Robert Newbury
(R)
Quan Nhu
(Q)
Anthony Olive
(A)
Oghenekpaobor Joel Oyibo
(OJ)
Allisa Paliana
(A)
Zhaoxing Pan
(Z)
Robbie Pesek
(R)
Kathryn Peterson
(K)
Heidi Poppendeck
(H)
Philip Putnam
(P)
Fabian Rivera
(F)
Marc Rothenberg
(M)
Amanda Rudman Spergel
(AR)
Kathleen Sable
(K)
Alain Schoepfer
(A)
Melissa Scott
(M)
Rachel Sheridan
(R)
Selma Sinanovic
(S)
Jonathan Spergel
(J)
Mary Jo Strobel
(MJ)
Kiki Sun
(K)
Amy Tasco
(A)
Crystal Tholen
(C)
Katherine Thompson
(K)
Tiffany Tomkinson
(T)
Daisy Tran
(D)
Alexandra Tylicki
(A)
Tiina Urv
(T)
Mei-Lun Wang
(ML)
Joshua Wechsler
(J)
Barry Wershil
(B)
Lisa Wheatley
(L)
Leah Wilkey
(L)
Guang-Yu Yang
(GY)
Angelika Zalewski
(A)
Amy Zicarelli
(A)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
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