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

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 12 months 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 12 months 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.