Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver · 2011
Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease.
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Clerici Mario, Cassinotti Andrea, Onida Francesco, Trabattoni Daria, Annaloro Claudio, Della Volpe Aldo, Rainone Veronica, Lissoni Francesca, Duca Piergiorgio, Sampietro Gianluca, Fociani Paolo, Vago Gianluca, Foschi Diego, Ardizzone Sandro, Deliliers Giorgio Lambertenghi, Porro Gabriele Bianchi
Аннотация
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.
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.
Предметные рубрики MeSH
AdultCD4 AntigensCD4-Positive T-LymphocytesCrohn DiseaseDrug ResistanceFemaleForkhead Transcription FactorsHematopoietic Stem Cell TransplantationHumansImmunomodulationInterferon-gammaInterleukin-10Interleukin-12Interleukin-2 Receptor alpha SubunitLongitudinal StudiesLymphocyte CountMaleMiddle AgedMonocytesT-Lymphocytes, RegulatoryToll-Like Receptor 2Toll-Like Receptor 4Transplantation, AutologousTumor Necrosis Factor-alpha