Immune reconstitution after autologous hematopoietic stem cell transplantation in Crohn’s disease: current status and future directions. A review on behalf of the EBMT Autoimmune Diseases Working Party and the autologous stem cell transplantation in refractory CD—low intensity therapy evaluation study investigators

Pockley, A.G. ORCID: 0000-0001-9593-6431, Lindsay, J.O., Foulds, G.A., Rutella, S. ORCID: 0000-0003-1970-7375, Gribben, J.G., Alexander, T. and Snowden, J.A., 2018. Immune reconstitution after autologous hematopoietic stem cell transplantation in Crohn’s disease: current status and future directions. A review on behalf of the EBMT Autoimmune Diseases Working Party and the autologous stem cell transplantation in refractory CD—low intensity therapy evaluation study investigators. Frontiers in Immunology, 9: 646. ISSN 1664-3224

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Abstract

Patients with treatment refractory Crohn’s disease (CD) suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity via the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD—Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT.

Item Type: Journal article
Publication Title: Frontiers in Immunology
Creators: Pockley, A.G., Lindsay, J.O., Foulds, G.A., Rutella, S., Gribben, J.G., Alexander, T. and Snowden, J.A.
Publisher: Frontiers Research Foundation
Date: 4 April 2018
Volume: 9
ISSN: 1664-3224
Identifiers:
NumberType
10.3389/fimmu.2018.00646DOI
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 05 Apr 2018 10:39
Last Modified: 05 Apr 2018 10:39
URI: http://irep.ntu.ac.uk/id/eprint/33188

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