Dataset Information

Mucosal Interleukin-10 depletion in steroid-refractory Crohn's disease patients.

ABSTRACT:

Background

Previous studies suggested that Interleukin-10 (IL-10) depletion in Crohn's disease (CD) could predict outcome.

Aim

To determine IL-10 in blood and at different intestinal locations in patients with active CD and to assess its potential prognostic capacity to identify aggressive CD.

Methods

Twenty-three patients with CD were included. Ulcerative colitis (UC), infectious colitis and healthy individuals acted as controls. Serum and mucosal samples were taken at baseline and 1 month after steroid initiation in CD patients. Patients were classified according to steroid response. Control samples were obtained from different intestinal locations. IL-10 expression was measured with real-time polymerase chain reaction, immunofluorescence (intestine) and ELISA (serum, biopsy cultures' supernatants and tissue homogenates).

Results

CD and UC showed an increase in IL-10 messenger RNA (mRNA) versus controls (p < .0001) in mucosa, whereas IL-10 protein secretion was increased in all types of intestinal inflammation (p < .001). No differences in IL-10 mRNA were found in CD at baseline regarding steroid response, but levels decreased in non-responders versus responders (p = .027) and were restored with rescue therapy. Serum IL-10 was increased in steroid-refractory CD at baseline and after treatment.

Conclusions

Abnormal IL-10 levels in refractory patients in both mucosa and blood have physiopathological relevance and may have potential clinical applications.

SUBMITTER: Carrasco A

PROVIDER: S-EPMC9514060 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Mucosal Interleukin-10 depletion in steroid-refractory Crohn's disease patients.

Carrasco Anna A Tristán Eva E Fernández-Bañares Fernando F Martín-Cardona Albert A Aceituno Montserrat M Zabana Yamile Y Fluvià Lourdes L Hernández José María JM Lorén Violeta V Manyé Josep J Salas Antonio A Andújar Xavier X Loras Carme C Esteve Maria M

Immunity, inflammation and disease 20221001 10

<h4>Background</h4>Previous studies suggested that Interleukin-10 (IL-10) depletion in Crohn's disease (CD) could predict outcome.<h4>Aim</h4>To determine IL-10 in blood and at different intestinal locations in patients with active CD and to assess its potential prognostic capacity to identify aggressive CD.<h4>Methods</h4>Twenty-three patients with CD were included. Ulcerative colitis (UC), infectious colitis and healthy individuals acted as controls. Serum and mucosal samples were taken at bas ...[more]

PMID: 36169258

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Project description:Background & aimsDurable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications.MethodsDNA from patients and their HLA-matched unrelated donors was genotyped and Polygenic Risk Scores calculated. Donor marrow was infused following non-myeloablative conditioning. Patient symptoms and endoscopic findings were documented at intervals after transplant.ResultsWe screened 807 patients, 143 of whom met eligibility criteria; 2 patients received allografts. Patient 1 had multiple complications and died at day 332 from respiratory failure. Patient 2 had resolution of CD symptoms until day 178 when CD recurred, associated with persistent host chimerism in both peripheral blood and intestinal mucosa. Withdrawal of immune suppression was followed by dominant donor immune chimerism in peripheral blood and resolution of CD findings. Over time, mucosal T-cells became donor-dominant. At 5 years after allografting, Patient 2 remained off all medications but had mild symptoms related to a jejunal stricture that required stricturoplasty at 6 years. At 8 years, she remains stable off medications.ConclusionsThe kinetics of immunologic chimerism after allogeneic marrow transplantation for CD patients depends on the intensity of the conditioning regimen and the magnitude of immune suppression. One patient achieved durable improvement of her previously refractory CD only after establishing donor immunologic chimerism in intestinal mucosa. Her course provides proof-of-principal for allografting as a potential treatment for refractory CD, but an immunoablative conditioning regimen should be considered for future studies.(ClinicalTrials.gov, NCT01570348).

Dataset Information

Mucosal Interleukin-10 depletion in steroid-refractory Crohn's disease patients.

Background

Aim

Methods

Results

Conclusions

Publications

Mucosal Interleukin-10 depletion in steroid-refractory Crohn's disease patients.

Similar Datasets

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