Background Patients with ulcerative colitis (UC) are often treated with biological therapies or small molecules. Knowledge about the impact of these therapies on the intestinal and peripheral blood immune cell composition is scarce. Therefore, we investigated how advanced therapies modulate immune cell distribution in UC patients. Methods We included 30 UC patients (53% male, median age 42 years) who started a biological or small molecule. Before the first drug administration, mucosal colonic biopsies and a peripheral blood sample were obtained. At the end of induction, colonic biopsies and peripheral blood were sampled again. Patients starting adalimumab (n=2), infliximab (n=3), vedolizumab (n=11), ustekinumab (n=6), ozanimod (n=2) and the JAK inhibitors filgotinib (n=3) and tofacitinib (n=3) were included. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0-1 at the end of induction. From the biopsies, a single-cell suspension was made. Intestinal and circulating immune cells were characterized via flow cytometry. Statistical analysis was performed using a paired t-test. Results Independent of the mechanism of action (MOA), patients responding to therapy showed a decrease of colonic granulocytes (neutrophils (p<0.0001) (Figure 1A), basophils (p<0.0001) (Figure 1B) and eosinophils (p=0.008) (Figure 1C)), active eosinophils (p=0.002) (Figure 1D)), B cells (p=0.05) (Figure 1E), regulatory T cells (p<0.0001) (Figure 1F) and T helper (Th) 2 cells (p=0.02) (Figure 1G), balanced with an increase of Th1 cells (p=0.03) (Figure 1H). In peripheral blood, eosinophils increased in patients not responding to therapy (p=0.05) (Figure 1I). Furthermore, we observed that only patients starting vedolizumab (n=11) showed a decrease in colonic eosinophils (p=0.02) (Figure 1J), active eosinophils (p=0.002) (Figure 1K), B cells (p=0.03) (Figure 1L) and T cells (p=0.004) (Figure 1M). Considering only non-vedolizumab patients (n=19), we did not observe this effect. Conclusion UC patients responding to advanced therapies showed a different intestinal immune cell distribution compared to non-responders, regardless of MOA. Vedolizumab therapy furthermore decreased several mucosal immune cell subsets that migrate to the gut through α4β7-MAdCAM-1 binding. While the effect of vedolizumab on B cells and T cells was previously described, we have now potentially identified an additional eosinophil-reducing effect in the colon.

中文翻译：

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P016 溃疡性结肠炎患者维多珠单抗治疗后粘膜（活性）嗜酸性粒细胞、B 细胞和 T 细胞减少

背景 溃疡性结肠炎（UC）患者通常接受生物疗法或小分子治疗。关于这些疗法对肠道和外周血免疫细胞组成的影响的知识很少。因此，我们研究了先进疗法如何调节 UC 患者的免疫细胞分布。方法 我们纳入了 30 名开始使用生物药物或小分子药物的 UC 患者（53% 为男性，中位年龄 42 岁）。在第一次给药之前，获得粘膜结肠活检和外周血样本。诱导结束时，再次采集结肠活检和外周血样本。开始使用阿达木单抗 (n=2)、英夫利昔单抗 (n=3)、维多珠单抗 (n=11)、乌特克单抗 (n=6)、奥扎尼莫德 (n=2) 以及 JAK 抑制剂非戈替尼 (n=3) 和托法替尼 (n=3) 的患者=3) 包括在内。内窥镜改善被定义为诱导结束时 Mayo 内窥镜分项评分为 0-1。从活组织检查中制成单细胞悬浮液。通过流式细胞术对肠道和循环免疫细胞进行表征。使用配对 t 检验进行统计分析。结果 与作用机制 (MOA) 无关，对治疗有反应的患者显示结肠粒细胞（中性粒细胞 (p<0.0001)（图 1A）、嗜碱性粒细胞 (p<0.0001)（图 1B）和嗜酸性粒细胞 (p=0.008) 减少） (图 1C))、活性嗜酸性粒细胞 (p=0.002) (图 1D))、B 细胞 (p=0.05) (图 1E)、调节性 T 细胞 (p<0.0001) (图 1F) 和 T 辅助细胞 (Th) 2细胞 (p=0.02) (图 1G)，与 Th1 细胞的增加相平衡 (p=0.03) (图 1H)。在外周血中，对治疗无反应的患者中嗜酸性粒细胞增加 (p=0.05)（图 1I）。此外，我们观察到，只有开始使用维多珠单抗的患者 (n=11) 表现出结肠嗜酸性粒细胞 (p=0.02) (图 1J)、活性嗜酸性粒细胞 (p=0.002) (图 1K)、B 细胞 (p=0.03) 的减少。图 1L) 和 T 细胞 (p=0.004) (图 1M)。仅考虑非维多珠单抗患者 (n=19)，我们没有观察到这种效应。结论 无论 MOA 为何，对先进疗法有反应的 UC 患者与无反应者相比，表现出不同的肠道免疫细胞分布。维多珠单抗治疗还减少了通过 α4β7-MAdCAM-1 结合迁移到肠道的几种粘膜免疫细胞亚群。虽然之前描述了维多珠单抗对 B 细胞和 T 细胞的影响，但我们现在可能发现了结肠中额外的嗜酸性粒细胞减少作用。