title: 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.
  
  
  OBJECTIVE
  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.
authors: Chair of Immunology, Department of Biomedical Sciences and Technologies, University of Milano, Milano, Italy. mario.clerici@unimi.it
authors: Mario
authors: M
authors: Clerici
authors: Andrea
authors: A
authors: Cassinotti
authors: Francesco
authors: F
authors: Onida
authors: Daria
authors: D
authors: Trabattoni
authors: Claudio
authors: C
authors: Annaloro
authors: Aldo
authors: A
authors: Della Volpe
authors: Veronica
authors: V
authors: Rainone
authors: Francesca
authors: F
authors: Lissoni
authors: Piergiorgio
authors: P
authors: Duca
authors: Gianluca
authors: G
authors: Sampietro
authors: Paolo
authors: P
authors: Fociani
authors: Gianluca
authors: G
authors: Vago
authors: Diego
authors: D
authors: Foschi
authors: Sandro
authors: S
authors: Ardizzone
authors: Giorgio Lambertenghi
authors: GL
authors: Deliliers
authors: Gabriele Bianchi
authors: GB
authors: Porro
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology* / Q000628:therapy*; D004351:Drug Resistance; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma