AIM:To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to antitumor necrosis factor-α (TNF-α) therapy.METHODS:Se...AIM:To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to antitumor necrosis factor-α (TNF-α) therapy.METHODS:Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy.The individual stage of immune activation was studied applying our new in vitro assay,in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ),interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)].The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent.RESULTS:Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e.CDEIS assessed before therapy (r=-0.621,P=0.013 and r=-0.625,P=0.013,respectively).FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r=-0.548,P=0.034).Low serum induced FOXP3 (r=-0.600,P=0.018) and GITR (r=-0.589,P=0.021) expression and low IFNγ secretion from target cells (r =-0.538,P=0.039) associated with treatment response detected as a decrease in CDEIS.CONCLUSION:The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.展开更多
AIM:To study the individual effects of glucocorticoid (GC) therapy on the state ofimmune activation in patient serum.METHODS:We developed a novel assay in which the effect of corticosteroid-treated patient serum on he...AIM:To study the individual effects of glucocorticoid (GC) therapy on the state ofimmune activation in patient serum.METHODS:We developed a novel assay in which the effect of corticosteroid-treated patient serum on healthy donor peripheral blood mononuclear cells (target cells) was studied,with a panel of markers for effector [interferon (IFN)γ and interleukin (IL)-5] and regulatory T cells (FOXP3 and glucocorticoid-induced tumor necrosis factor receptor,GITR).The study group comprised 19 children with inflammatory bowel disease.The individual effect of patient serum on target cells was analyzed prior to GC therapy and 2 wk later.RESULTS:The effect of GC therapy mediated by patient serum was seen as a decrease in the target cells expression of regulatory T-cell-related markers GITR (median suppression 24%,range of suppression 1%-63%,in 2 cases increase of 6% and 77%,P < 0.01 for mitogen-activated target cells) and FOXP3 (median suppression 33%,range of suppression 0%-79%,in one case an increase of 173%,P < 0.05 for resting cells),and secretion of IFNγ [from a mean of 87 700 pg/mL (SD 33 900 pg/mL) to 60 900 pg/mL (SD 44 200 pg/mL) in mitogen-activated target cells,13 of the cases showed a decrease,P < 0.01].The total or weight-related prednisolone dose did not correlate with the patient-seruminduced changes in the target cell markers.CONCLUSION:GC response could be monitored at an individual level by studying the effect of patient serum on signaling pathways of target immune cells.展开更多
基金Supported by The Finnish Cultural Foundationthe Finnish Pediatric Research Foundation+3 种基金the Pivikki and Sakari Sohlberg Foundationthe Helsinki University Central Hospital Grantthe Orion-Farmos Research Foundationthe Maryand George C Ehrnrooth Foundation
文摘AIM:To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to antitumor necrosis factor-α (TNF-α) therapy.METHODS:Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy.The individual stage of immune activation was studied applying our new in vitro assay,in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ),interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)].The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent.RESULTS:Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e.CDEIS assessed before therapy (r=-0.621,P=0.013 and r=-0.625,P=0.013,respectively).FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r=-0.548,P=0.034).Low serum induced FOXP3 (r=-0.600,P=0.018) and GITR (r=-0.589,P=0.021) expression and low IFNγ secretion from target cells (r =-0.538,P=0.039) associated with treatment response detected as a decrease in CDEIS.CONCLUSION:The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.
基金Supported by The Finnish Cultural Foundation,the Finnish Pediatric Research Foundation,the Pivikki and Sakari Sohlberg Foundation,and the Orion Research Foundation
文摘AIM:To study the individual effects of glucocorticoid (GC) therapy on the state ofimmune activation in patient serum.METHODS:We developed a novel assay in which the effect of corticosteroid-treated patient serum on healthy donor peripheral blood mononuclear cells (target cells) was studied,with a panel of markers for effector [interferon (IFN)γ and interleukin (IL)-5] and regulatory T cells (FOXP3 and glucocorticoid-induced tumor necrosis factor receptor,GITR).The study group comprised 19 children with inflammatory bowel disease.The individual effect of patient serum on target cells was analyzed prior to GC therapy and 2 wk later.RESULTS:The effect of GC therapy mediated by patient serum was seen as a decrease in the target cells expression of regulatory T-cell-related markers GITR (median suppression 24%,range of suppression 1%-63%,in 2 cases increase of 6% and 77%,P < 0.01 for mitogen-activated target cells) and FOXP3 (median suppression 33%,range of suppression 0%-79%,in one case an increase of 173%,P < 0.05 for resting cells),and secretion of IFNγ [from a mean of 87 700 pg/mL (SD 33 900 pg/mL) to 60 900 pg/mL (SD 44 200 pg/mL) in mitogen-activated target cells,13 of the cases showed a decrease,P < 0.01].The total or weight-related prednisolone dose did not correlate with the patient-seruminduced changes in the target cell markers.CONCLUSION:GC response could be monitored at an individual level by studying the effect of patient serum on signaling pathways of target immune cells.
