Chie Kurihara, Toshihide Ohmori, Hirotaka Furuhashi, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Gastroenterology 2019 156 (6) Suppl. S-1146
Tu1846 Higher TNFα and Mip-1β Expression in Pretreatment Colonic Mucosa Have Potential to Predict of Achieving Mucosal Healing by Granulocyte and Monocyte Adsorptive Apheresis Therapy in Ulcerative Colitis Patients
Background: Granulocyte and monocyte adsorptive apheresis (GMA) is non-pharmacological therapy which selective depletion of activated granulocytes and monocytes/macrophages from peripheral blood. GMA is effective and safe as induction therapy in ulcerative colitis (UC) of moderate to severe patients, and commonly used in Asia and north Europe. However, therapeutic mechanism of GMA, especially its effect on mucosal healing, has not been well characterized. Since moderate to severe patients with UC sometimes become fulminant, it is important to select an appropriate induction therapy. GMA treatment efficacy is reported about 60% patients respond, whereas, there is not useful parameter that predicts GMA therapeutic efficacy before treatment. In this study, we attempted to identify predictive factors of clinical response to GMA treatment in UC patients. Methods: Thirty-two active UC patients (Mayo score ^ 5 and Mayo endoscopic score ^ 2) and 10 non-IBD control subjects were enrolled in this study. All UC patients received 10 or 11 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Control subjects underwent colonoscopies for screening of colon cancer. Assessment of disease activity and colonic mucosal healing were determined based on Mayo score. Inflammation-related molecules mRNA expressions were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. ROC curves analysis was used to assess sensitivity and specificity in prediction of GMA therapeutic efficacy. Results: GMA treatment efficacy is 11 patients (34.4%) achieved clinical remission, 17 patients (53.1%) were response and 4 patients (12.5%) were non-response. Mucosal healing was observed in 18 patients (56.3%) and it was not observed in 14 patients (43.7%). Baseline characteristics were not significantly different according to GMA efficacy. Before the first GMA session, the clinical remission group showed significantly higher expressions of TNFα, MAdCAM-1 and MIP-1β mRNA than those of the non-response group (P <0.05). Patients in the response group who highly expressed these mRNA achieved mucosal healing. In the mucosal healing group, the mRNA levels of TNFα, IL-1β, IL-8, MIP-1β, TGFβ and IL-10 were significantly higher than those in the non-mucosal healing group (P <0.05). TNFα and MIP-1β had 0.83 and 0.79 of area under the curve with 83.3% and 66.7% sensitivity, 71.4% and 100% specificity, 78.9% and 100%positive predictive value, and 76.9% and 70.0% negative predictive value, respectively, for prediction of mucosal healing. Conclusion: Mucosal expression of TNFα and MIP-1β mRNA before treatment in the remission group and the mucosal healing group was significantly higher than non-responder to GMA treatment. We propose that measuring of these molecules’ expression is useful to expect GMA therapeutic efficacy in patients with UC.
Tu1846 Higher Expression of MIP-1β and IL23 in Colonic Mucosa of Pretreatment may Predict Therapeutic Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Elderly Patients with Ulcerative Colitis
Chie Kurihara Toshihide Ohmori Shingo Kato Koji Yakabi Satoshi Mochida Soichiro Miura Gastroenterology 2017 152 (5) Suppl. S764
Background: The number of the elderly patients of ulcerative colitis (UC) is growing as the population ages. Because elderly patients with UC sometimes become refractory to treatment, it is important to select an appropriate induction therapy for elderly patients at the early phase of UC disease. To predict which therapy is effective before treatment will be useful for the decision of later therapeutic strategy. Granulocyte and monocyte adsorptive apheresis (GMA) that was developed for selective depletion of activated granulocytes and monocytes/
macrophages from peripheral blood is non-pharmacological therapy for inflammatory bowel disease. It is beneficial than the other therapy in the point that it has fewer side effects. GMA is effective and safe as induction therapy in UC, and commonly used in Asia and north Europe. GMA is one of hopeful candidate of elderly therapy. We investigated the relationship between therapeutic efficacy of GMA and age, and examined whether mRNA expressions of cytokines and chemokines in colonic mucosa showed presence of age-related change. Methods: Thirty-two active UC patients, mean age 36.7 years, range 14-70 years, were enrolled in this study. All patients received 10 or 11 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Assessment of disease activity and colonic mucosal healing were determined based on Mayo score. In this study, elderly patients were defined as those >55 years of age. mRNA expressions of cytokines and chemokines were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: There were no significant differences in sex, duration of disease, location of disease, CRP, WBC and Mayo score before the first GMA treatment between elderly group and non-elderly group. After the last GMA session, the ratios of mucosal healing in elderly group and non-elderly group were 2 of 6 (33.3%) and 16 of 26 (61.5%), respectively. In all patients, before treatment of GMA, mucosal healing group showed significantly higher mRNA expression of inflammatory cytokines and chemokines such as MIP-1β, TNFα, IL1β and IL8 in colonic mucosal tissue than that of non-mucosal healing group (P <0.05). In particular, in elderly group, the degree of mRNA expression of MIP-1β and IL23 in colonic mucosa before GMA treatment was higher in mucosal healing group than in non-mucosal healing group (P <0.05). High expressions of MIP-1β and IL23 showed sensitivity, specificity, positive predictive value and negative predictive value of 100% as a marker of mucosal healing after GMA in elderly group. Conclusion: Mucosal IL23 and MIP-1β mRNA expression before treatment in elderly were significantly higher in responder than non-responder to GMA treatment. We propose that measuring of expression of these molecules is useful to expect therapeutic efficacy of GMA in elderly patients with UC.
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