Innate Immunity Activation in Newly Diagnosed Ileocolonic Crohn's Disease: A Cohort Study.
Journal
Diseases of the colon and rectum
ISSN: 1530-0358
Titre abrégé: Dis Colon Rectum
Pays: United States
ID NLM: 0372764
Informations de publication
Date de publication:
06 Feb 2024
06 Feb 2024
Historique:
medline:
6
2
2024
pubmed:
6
2
2024
entrez:
6
2
2024
Statut:
aheadofprint
Résumé
Recent studies showed that early surgery for Crohn's disease leads to a lower recurrence rate. However, the underlying mechanism is unknown. The study aims to analyze the innate immunity microenvironment in ileal mucosa according to Crohn's disease duration. A prospective cohort study. Tertiary referral center for IBD surgery. A total of 88 consecutive Crohn's disease patients undergoing ileocolonic resection were prospectively enrolled. Mucosal samples were obtained from both healthy and inflamed ileum. Data from a public dataset were analyzed as an external validation cohort. Neutrophil infiltration was evaluated at histology and macrophage subpopulation at immunohistochemistry. Expression of TLR2, TLR4, TLR5, DEFB1, DEFB4A, DEFB103, DEFA5 and DEFA6 was quantified by Real-Time qPCR. Concentrations of BDNF, CCL11, ICAM1, IL1A, IL1B, IL1RN, IL12 p40, IL12 p70, IL15, IL17A, IL23A, MMP3, CCL3, KITLG, VEGFA were determined with immunometric assay. Neutrophil infiltration is inversely correlated with disease duration. DEFB4A mRNA expression tended to be higher in late-stage Crohn's disease (p = 0.07). A higher number of macrophages expressed CD163 at low intensity in the late stage (p = 0.04). The concentration of IL15 (p = 0.02) and IL23A (p = 0.05) was higher in healthy ileal mucosa of early-stage patients. In the external cohort, expression of DEFB1 (p = 0.03) and DEFB4A (p = 0.01), IL2 (p = 0.04), and IL3 (p = 0.03) increased in late-stage patients. A relatively small number of patients, especially in the newly diagnosed group. In newly diagnosed Crohn's disease, high levels of IL-15 and IL-23 in healthy mucosa suggest that innate immunity is the starter of acute inflammation. Moreover, M2 macrophages increase in healthy mucosa of late-stage Crohn's disease patients suggesting that reparative and profibrotic processes are predominant in the long term and in this phase, anti-inflammatory therapy may be less efficient. See Video Abstract.
Sections du résumé
BACKGROUND
BACKGROUND
Recent studies showed that early surgery for Crohn's disease leads to a lower recurrence rate. However, the underlying mechanism is unknown.
OBJECTIVE
OBJECTIVE
The study aims to analyze the innate immunity microenvironment in ileal mucosa according to Crohn's disease duration.
DESIGN
METHODS
A prospective cohort study.
SETTINGS
METHODS
Tertiary referral center for IBD surgery.
PATIENTS
METHODS
A total of 88 consecutive Crohn's disease patients undergoing ileocolonic resection were prospectively enrolled. Mucosal samples were obtained from both healthy and inflamed ileum. Data from a public dataset were analyzed as an external validation cohort.
MAIN OUTCOME MEASURES
METHODS
Neutrophil infiltration was evaluated at histology and macrophage subpopulation at immunohistochemistry. Expression of TLR2, TLR4, TLR5, DEFB1, DEFB4A, DEFB103, DEFA5 and DEFA6 was quantified by Real-Time qPCR. Concentrations of BDNF, CCL11, ICAM1, IL1A, IL1B, IL1RN, IL12 p40, IL12 p70, IL15, IL17A, IL23A, MMP3, CCL3, KITLG, VEGFA were determined with immunometric assay.
RESULTS
RESULTS
Neutrophil infiltration is inversely correlated with disease duration. DEFB4A mRNA expression tended to be higher in late-stage Crohn's disease (p = 0.07). A higher number of macrophages expressed CD163 at low intensity in the late stage (p = 0.04). The concentration of IL15 (p = 0.02) and IL23A (p = 0.05) was higher in healthy ileal mucosa of early-stage patients. In the external cohort, expression of DEFB1 (p = 0.03) and DEFB4A (p = 0.01), IL2 (p = 0.04), and IL3 (p = 0.03) increased in late-stage patients.
LIMITATIONS
CONCLUSIONS
A relatively small number of patients, especially in the newly diagnosed group.
CONCLUSIONS
CONCLUSIONS
In newly diagnosed Crohn's disease, high levels of IL-15 and IL-23 in healthy mucosa suggest that innate immunity is the starter of acute inflammation. Moreover, M2 macrophages increase in healthy mucosa of late-stage Crohn's disease patients suggesting that reparative and profibrotic processes are predominant in the long term and in this phase, anti-inflammatory therapy may be less efficient. See Video Abstract.
Identifiants
pubmed: 38319717
doi: 10.1097/DCR.0000000000003145
pii: 00003453-990000000-00552
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © The ASCRS 2024.