INTRODUCTION In patients with ulcerative colitis (UC), dysplasia develops in 10%-20% of cases. The persistence of low-grade dysplasia (LGD) in UC in 2 consecutive observations is still an indication for restorative proctocolectomy. Our hypothesis is that in the case of weak cytotoxic activation, dysplasia persists. We aimed to identify possible immunological markers of LGD presence and persistence. METHODS We prospectively enrolled 112 UC patients who underwent screening colonoscopy (T0) who had biopsies taken from their sigmoid colon. Ninety of them had at least a second colonoscopy (T1) with biopsies taken in the sigmoid colon and 8 patients had dysplasia in both examinations suggesting a persistence of LGD in their colon. Immunohistochemistry and real time polymerase chain reaction for CD4, CD69, CD107, and CD8β messenger RNA (mRNA) expression and flow cytometry for epithelial cells expressing CD80 or HLA avidin-biotin complex were performed. Non-parametric statistics, receiver operating characteristic curves analysis, and logistic multiple regression analysis were used. RESULTS Thirteen patients had LGD diagnosed at T0. The mucosal mRNA expression of CD4, CD69, and CD8β was significantly lower than in patients without dysplasia (P = 0.033, P = 0.046 and P = 0.007, respectively). A second colonoscopy was performed in 90 patients after a median follow-up of 17 (12-25) months and 14 of the patients were diagnosed with LGD. In these patients, CD8β mRNA expression at T0 was significantly lower in patients without dysplasia (P = 0.004). A multivariate survival analysis in a model including CD8β mRNA levels and age >50 demonstrated that both items were independent predictors of dysplasia at follow-up (hazard ratio [HR] = 0.47 [95% confidence interval [CI]: 0.26-0.86], P = 0.014, and HR = 13.32 [95% CI: 1.72-102.92], P = 0.013). DISCUSSION These data suggest a low cytotoxic T cell activation in the colonic mucosa of UC patients who do not manage to clear dysplasia. Thus, low level of CD8β mRNA expression in non-dysplastic colonic mucosa might be considered in future studies about the decision making of management of LGD in UC.

中文翻译：

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弱的细胞毒性T细胞活化可预测溃疡性结肠炎的低度异型增生持续性。

简介在溃疡性结肠炎（UC）患者中，发育异常的发生率占10％-20％。连续2次观察到UC中存在低度不典型增生（LGD），这仍然是恢复性结肠直肠癌切除术的指标。我们的假设是，在细胞毒性激活较弱的情况下，发育异常持续存在。我们旨在确定LGD存在和持续存在的可能的免疫学标记。方法我们前瞻性招募了112例行结肠镜检查（T0）并从乙状结肠进行活检的UC患者。他们中至少有90人进行了第二次结肠镜检查（T1），并在乙状结肠中进行了活检，并且8位患者在两次检查中均出现了不典型增生，表明LGD在其结肠中持续存在。CD4，CD69，CD107的免疫组织化学和实时聚合酶链反应 对表达CD80或HLA抗生物素蛋白-生物素复合物的上皮细胞进行CD8β信使RNA（mRNA）表达和流式细胞术。使用非参数统计，接收器工作特性曲线分析和逻辑多元回归分析。结果13例T0确诊为LGD。CD4，CD69和CD8β的粘膜mRNA表达显着低于无发育异常的患者（分别为P = 0.033，P = 0.046和P = 0.007）。在中位随访17（12-25）个月后，对90例患者进行了第二次结肠镜检查，其中14例被诊断为LGD。在这些患者中，无发育异常的患者在T0时CD8βmRNA表达明显降低（P = 0.004）。模型中的多变量生存分析，包括CD8βmRNA水平和年龄> 50个研究表明，这两项都是随访时发育异常的独立预测因子（危险比[HR] = 0.47 [95％置信区间[CI]：0.26-0.86]，P = 0.014和HR = 13.32 [95％CI：1.72] -102.92]，P = 0.013）。讨论这些数据表明，UC患者结肠粘膜细胞毒性T细胞活化程度较低，这些患者未能清除异型增生。因此，在未来关于UC LGD决策管理的研究中，可能会考虑非增生性结肠黏膜中CD8βmRNA表达的低水平。