Scientific corner


Chie Kurihara, Toshihide Ohmori, Kenichi Inaba, Nao Sugihara, Yoshinori Hanawa, Kazuki Horiuchi, Akinori Wada, Shin Nishii, Akinori Mizoguchi, Suguru Ito, Rina Tanemoto, Akira Tomioka, Yoshikiyo Okada, Yoshihiro Akita, Kazuyuki Narimatsu, Masaaki Higashiyama, Shunsuke Komoto, Kengo Tomita, Ryota Hokari

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is non-pharmacological therapy which selective depletion of activated granulocytes and monocytes/macrophages from peripheral blood, and it is used as induction therapy for IBD. However, its therapeutic mechanism has not been well characterized. Recently, mucosal healing has been emerged as a therapeutic goal for IBD. It has been reported that growth factors play a role in improvement of mucosal repair and regeneration in animal colitis models, and tight junction proteins which impact mucosal permeability play a crucial role in mucosal healing. We investigated that changes in mRNA expression levels of these molecules in colonic mucosa of ulcerative colitis (UC) patients before and after GMA treatment in order to obtain further understanding of GMA therapeutic mechanisms. Methods: Thirty-two active UC patients (Mayo score ≥ 5 and Mayo endoscopic score ≥ 2) were enrolled in this study. All UC patients received 10-11 times of GMA, and colonoscopies were applied before the first GMA (preGMA) and after the last GMA (post-GMA). Assessment of GMA therapeutic efficacy and colonic mucosal healing were determined based on Mayo score. Growth factors such as EGF and HGF, and tight junction proteins such as occludin and ZO-1 mRNA expressions were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: After GMA treatment, 11 patients (34.4%) achieved clinical remission, 17 patients (53.1%) showed clinical response and 4 patients (12.5%) showed non-response. All patients of the clinical remission group achieved mucosal healing, whereas none of patients in non-response group achieved mucosal healing. Baseline characteristics such as sex, location of disease, CRP, WBC and Mayo score were not significantly different according to GMA efficacy. In both pre-GMA and post-GMA, the clinical remission group showed significantly higher expressions of occludin, ZO-1 and EGF mRNA in mucosal tissue than those of the nonresponse group (P <0.05). Post-GMA, HGF mRNA expression tended to be lower in the remission group than those in non-response group. In the non-response group, levels of occludin and ZO-1 mRNA significantly decreased post-GMA compared to their pre-GMA levels (P <0.05), but they were not decreased in the clinical remission group. In contrast, HGF mRNA level decreased post-GMA compared to its pre-GMA level in the remission group, but it was not decreased in the non-response group. Conclusion: In UC patients who achieved clinical remission by GMA, expressions of EGF and tight junction molecules were higher significantly, and mRNA level of HGF decreased after GMA treatment. These results suggest that these molecules play an important role in mucosal healing, and could be helpful for choosing patients who are respond to GMA before treatment

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