Chair of Immunology, Department of Biomedical Sciences and Technologies, University of Milano, Milano, Italy.
Dig Liver Dis. 2011 Dec;43(12):946-52. doi: 10.1016/j.dld.2011.07.021. Epub 2011 Sep 9.
Autologous haematopoietic stem cells transplantation (HSCT) has been shown to be effective in refractory Crohn's disease.
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.
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.
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.
HSCT can induce and maintain clinical and endoscopic remission in refractory Crohn's disease, which is associated with immunomodulation.
自体造血干细胞移植（HSCT）已被证明对难治性克罗恩病有效。
我们分析了 HSCT 对接受多种药物治疗难治或不耐受的中重度克罗恩病患者免疫反应的影响。
在环磷酰胺（CTX）和 G-CSF 动员后采集未选择的外周血干细胞。预处理方案包括 CTX 和兔抗胸腺球蛋白。在移植前、动员后以及移植后 3、6 和 12 个月采集免疫分析用血液样本。免疫分析评估：（1）CD4+/CD25 高表达/FoxP3+调节性 T 细胞（Tregs）；（2）Toll 样受体 2（TLR2）和 TLR4 表达的单核细胞（CD14+细胞）；（3）CD14+细胞刺激物产生的 IL-12、IL-10、TNF-α和 CD4+T 细胞产生的 IFN-γ。将免疫结果与健康供体进行比较，并与 12 个月随访期间的临床和内镜反应相关联。
总体而言，Tregs 增加，而 TLR4 表达细胞以及 TNF-α和 IL-10 均高于基线时的健康供体，移植后显著降低。T（3）时完全缓解者 Tregs 更高，IFN-γ和 IL12 更低。唯一复发患者的 Tregs 减少，IL12 和 TLR2 增加。
HSCT 可诱导并维持难治性克罗恩病的临床和内镜缓解，这与免疫调节有关。
