TY - JOUR
T1 - Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease
AU - Clerici, Mario
AU - Cassinotti, Andrea
AU - Onida, Francesco
AU - Trabattoni, Daria
AU - Annaloro, Claudio
AU - Della Volpe, Aldo
AU - Rainone, Veronica
AU - Lissoni, Francesca
AU - Duca, Piergiorgio
AU - Sampietro, Gianluca
AU - Fociani, Paolo
AU - Vago, Gianluca
AU - Foschi, Diego
AU - Ardizzone, Sandro
AU - Deliliers, Giorgio Lambertenghi
AU - Porro, Gabriele Bianchi
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - Immunomodulation
KW - Refractory disease
KW - Stem cells
KW - Transplantation
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U2 - 10.1016/j.dld.2011.07.021
DO - 10.1016/j.dld.2011.07.021
M3 - Article
C2 - 21907652
AN - SCOPUS:80055072032
VL - 43
SP - 946
EP - 952
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
SN - 1590-8658
IS - 12
ER -