TY - JOUR
T1 - Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease
AU - Van den Brande, Jan M. H.
AU - Koehler, Tamara C.
AU - Zelinkova, Zuzana
AU - Bennink, Roelof J.
AU - Velde, Anje A. te
AU - ten Cate, Fibo J. W.
AU - van Deventer, Sander J. H.
AU - Peppelenbosch, Maikel P.
AU - Hommes, Daniel W.
PY - 2007/4
Y1 - 2007/4
N2 - Background: The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro.Aim: To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease.Methods: (99m)Technetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohns Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of > 100 points).Results: Colonic uptake of Tc-99m-annexin V significantly increased in 2,4,6- trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of T-99m-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic 99mTc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41(0.07) (p <0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of 99mTc-annexin V could be detected in 10 of the 14 responding patients (CDAI.100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis.Conclusions: These in vivo observations support the notion that colonic uptake of 99mTc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.
AB - Background: The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro.Aim: To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease.Methods: (99m)Technetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohns Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of > 100 points).Results: Colonic uptake of Tc-99m-annexin V significantly increased in 2,4,6- trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of T-99m-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic 99mTc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41(0.07) (p <0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of 99mTc-annexin V could be detected in 10 of the 14 responding patients (CDAI.100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis.Conclusions: These in vivo observations support the notion that colonic uptake of 99mTc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.
KW - CHIMERIC MONOCLONAL-ANTIBODY
KW - RADIOLABELED ANNEXIN-V
KW - INFLIXIMAB INDUCES APOPTOSIS
KW - CASPASE-DEPENDENT PATHWAY
KW - PROPRIA T-LYMPHOCYTES
KW - IN-VIVO DETECTION
KW - FACTOR-ALPHA CA2
KW - TNF-ALPHA
KW - RHEUMATOID-ARTHRITIS
KW - CELL-DEATH
U2 - 10.1136/gut.2006.105379
DO - 10.1136/gut.2006.105379
M3 - Article
SN - 0017-5749
VL - 56
SP - 509
EP - 517
JO - Gut
JF - Gut
IS - 4
ER -