Beatriz Mateos1, Esteban Sáez-González1,2, Inés Moret1,2,3, David Hervás4, Marisa Iborra1,2,3, Elena Cerrillo1,2, Luis Tortosa1,2,3, Pilar Nos1,2,3, Belén Beltrán5,6,7. 1. Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain. 2. Inflammatory Bowel Disease Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain. 3. Centro de Investigación Biomédica en Red de Enfermedades hepáticas y Digestivas (CIBEREHD), Madrid, Spain. 4. Biostatictics Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain. 5. Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain, belenbeltranniclos@gmail.com. 6. Inflammatory Bowel Disease Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain, belenbeltranniclos@gmail.com. 7. Centro de Investigación Biomédica en Red de Enfermedades hepáticas y Digestivas (CIBEREHD), Madrid, Spain, belenbeltranniclos@gmail.com.
Abstract
BACKGROUND: Cytokines emerge as possible biomarkers of response in Crohn's disease (CD). We aimed to determine the plasmatic cytokine profiles of active CD patients who started infliximab (IFX) treatment and their capacity to predict the response to IFX. METHODS: A total of 30 active CD patients receiving an induction therapy of IFX were enrolled in the study. Peripheral blood samples pretreatment were collected. Concentrations of 15 cytokines were measured by Luminex technology. Responses to IFX were evaluated by the drop in fecal calprotectin based on its logarithm-transformed values. A random forest (RF) predictive model was used for data analyses. RESULTS: Samples of 22 patients were analyzed. The RF model ranked the following cytokines as the top predictors of the response: tumor necrosis factor alpha (TNFα), interleukin (IL)-13, oncostatin M (OSM), and IL-7 (p < 0.005). Partial dependency plots showed that high levels of IL-13 pretreatment, low TNFα levels, and low IL-7 levels were associated with a favorable IFX response. Increased levels of OSM and TNFα predicted unfavorable responses to IFX. CONCLUSIONS: We here show that a log drop in calprotectin strongly correlates with clinical parameters and it can be proposed as a useful objective clinical response predictor. Plasma TNFα, IL-13, Il-7, and OSM network could predict CD response to IFX before induction therapy, as assessed by calprotectin log drop.
BACKGROUND: Cytokines emerge as possible biomarkers of response in Crohn's disease (CD). We aimed to determine the plasmatic cytokine profiles of active CDpatients who started infliximab (IFX) treatment and their capacity to predict the response to IFX. METHODS: A total of 30 active CDpatients receiving an induction therapy of IFX were enrolled in the study. Peripheral blood samples pretreatment were collected. Concentrations of 15 cytokines were measured by Luminex technology. Responses to IFX were evaluated by the drop in fecal calprotectin based on its logarithm-transformed values. A random forest (RF) predictive model was used for data analyses. RESULTS: Samples of 22 patients were analyzed. The RF model ranked the following cytokines as the top predictors of the response: tumor necrosis factor alpha (TNFα), interleukin (IL)-13, oncostatin M (OSM), and IL-7 (p < 0.005). Partial dependency plots showed that high levels of IL-13 pretreatment, low TNFα levels, and low IL-7 levels were associated with a favorable IFX response. Increased levels of OSM and TNFα predicted unfavorable responses to IFX. CONCLUSIONS: We here show that a log drop in calprotectin strongly correlates with clinical parameters and it can be proposed as a useful objective clinical response predictor. Plasma TNFα, IL-13, Il-7, and OSM network could predict CD response to IFX before induction therapy, as assessed by calprotectin log drop.
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