Background: Autologous haematopoietic stem cells transplantation (HSCT) has been shown to be effective in refractory Crohn's disease. Aim: We analysed the effects of HSCT on the immune response of patients treated for moderate-severe Crohn's disease, refractory or intolerant to multiple drugs. Methods: Unselected peripheral blood stem cells were collected after mobilisation with cyclophosphamide (CTX) and G-CSF. The conditioning regimen included CTX and rabbit antithymocyte globulin. Blood samples for immunological analyses were collected at baseline, after mobilisation, and 3, 6 and 12months after transplantation. Immunological analyses evaluated: (1) CD4 +/CD25 high+/FoxP3 + regulatory T cells (T-regs); (2) Toll-like receptor 2-(TLR2) and TRL4-expressing monocytes (CD14 + cells); (3) IL-12, IL-10, TNF-alpha-production by mitogen-stimulated CD14 + cells and IFN-gamma production by CD4 + T cells. Immunological results were compared with healthy donors and associated with clinical and endoscopic response during 12months of follow-up. Results: Overall, T-regs increased, whilst TLR4-expressing cells, as well as TNF-alpha and IL-10, all higher than healthy donors at baseline, significantly decreased after transplantation. Full responders at T 3 had higher T-regs and lower IFN-gamma and IL12. T-regs decreased and IL12 and TLR2 increased in the only relapsed patient. Conclusions: HSCT can induce and maintain clinical and endoscopic remission in refractory Crohn's disease, which is associated with immunomodulation.

Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease / M.S. Clerici, A. Cassinotti, F. Onida, D. Trabattoni, C. Annaloro, A. Della Volpe, V. Rainone, F. Lissoni, P. Duca, G. Sampietro, P. Fociani, G. Vago, D. Foschi, S. Ardizzone, G. Lambertenghi Deliliers, G. Bianchi Porro. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - 43:12(2011 Dec), pp. 946-952.

Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease

M.S. Clerici;F. Onida;D. Trabattoni;V. Rainone;P. Duca;G. Vago;D. Foschi;S. Ardizzone;G. Bianchi Porro
2011

Abstract

Background: Autologous haematopoietic stem cells transplantation (HSCT) has been shown to be effective in refractory Crohn's disease. Aim: We analysed the effects of HSCT on the immune response of patients treated for moderate-severe Crohn's disease, refractory or intolerant to multiple drugs. Methods: Unselected peripheral blood stem cells were collected after mobilisation with cyclophosphamide (CTX) and G-CSF. The conditioning regimen included CTX and rabbit antithymocyte globulin. Blood samples for immunological analyses were collected at baseline, after mobilisation, and 3, 6 and 12months after transplantation. Immunological analyses evaluated: (1) CD4 +/CD25 high+/FoxP3 + regulatory T cells (T-regs); (2) Toll-like receptor 2-(TLR2) and TRL4-expressing monocytes (CD14 + cells); (3) IL-12, IL-10, TNF-alpha-production by mitogen-stimulated CD14 + cells and IFN-gamma production by CD4 + T cells. Immunological results were compared with healthy donors and associated with clinical and endoscopic response during 12months of follow-up. Results: Overall, T-regs increased, whilst TLR4-expressing cells, as well as TNF-alpha and IL-10, all higher than healthy donors at baseline, significantly decreased after transplantation. Full responders at T 3 had higher T-regs and lower IFN-gamma and IL12. T-regs decreased and IL12 and TLR2 increased in the only relapsed patient. Conclusions: HSCT can induce and maintain clinical and endoscopic remission in refractory Crohn's disease, which is associated with immunomodulation.
Crohn's disease; Immunomodulation; Refractory disease; Stem cells; Transplantation
Settore MED/12 - Gastroenterologia
Settore MED/18 - Chirurgia Generale
Settore MED/01 - Statistica Medica
Settore MED/04 - Patologia Generale
Settore MED/15 - Malattie del Sangue
dic-2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/176375
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