ABSTRACT

Background: Loss of immune homeostasis to enteric pathogens is considered to be involved in the pathogenesis of ulcerative colitis (UC), and regulatory T cells (Tregs) are key for this immune homeostasis. Helios exhibits an important effect on regulating the suppressive function of Tregs. Epstein–Barr virus (EBV) is more commonly detected in UC. However, whether there is an association between EBV infection and Helios⁺Tregs and its impact on disease activity of UC remain unclear. We aimed to explore the clinical significance of Helios⁺Tregs and their potential association with EBV infection in UC.

Methods: Seventy-six UC patients and 38 controls were consecutively enrolled. Helios⁺FoxP3⁺Tregs were analyzed using flow cytometry and compared among groups. Eight active UC patients treated with 5-aminosalicylic acid were followed up. Correlation analyses were conducted between Helios⁺FoxP3⁺Tregs and disease activity indicators. In addition, EBV viral loads in the mucosal lesion were quantified in active UC by quantitative polymerase chain reaction and were comprehensively analyzed in subgroups of different disease severity, and their associations with Helios⁺FoxP3⁺Tregs were also analyzed.

Results: Helios⁺FoxP3⁺Tregs were significantly decreased in active UC and were inversely correlated with serum C-reactive protein and Mayo score. Moreover, we observed the recovery of Helios⁺FoxP3⁺Tregs in followed-up active UC achieving remission after treatment. EBV loads were higher in active UC, and levels of Helios⁺FoxP3⁺Tregs in the EBV-positive subgroup were lower than the EBV-negative subgroup in moderate and severe active patients. Most importantly, we found that Helios⁺FoxP3⁺Tregs were significantly negatively correlated with EBV viral loads.

Conclusion: Helios⁺FoxP3⁺Tregs are likely to play a pivotal role in disease activity of UC and may be influenced by EBV infection.

摘要

背景：肠道病原体的免疫稳态丧失被认为与溃疡性结肠炎 (UC) 的发病机制有关，而调节性 T 细胞 (Tregs) 是这种免疫稳态的关键。Helios 在调节 Tregs 的抑制功能方面具有重要作用。爱泼斯坦-巴尔病毒 (EBV) 在 UC 中更常见。然而，EBV 感染与 Helios ⁺ Tregs之间是否存在关联及其对 UC 疾病活动的影响尚不清楚。我们旨在探讨 Helios ⁺ Tregs的临床意义及其与 UC 中 EBV 感染的潜在关联。

方法：连续入组UC患者76例，对照组38例。使用流式细胞术分析Helios ⁺ FoxP3 ⁺ Tregs 并在组间进行比较。对 8 名接受 5-氨基水杨酸治疗的活动性 UC 患者进行了随访。在 Helios ⁺ FoxP3 ⁺ Tregs 和疾病活动指标之间进行了相关分析。此外，通过定量聚合酶链反应在活动性UC中量化粘膜病变中的EBV病毒载量，并在不同疾病严重程度的亚组中进行综合分析，还分析了它们与Helios ⁺ FoxP3 ⁺ Tregs的关联。

结果：Helios ⁺ FoxP3 ⁺ Tregs 在活动性 UC 中显着降低，与血清 C 反应蛋白和 Mayo 评分呈负相关。此外，我们观察到 Helios ⁺ FoxP3 ⁺ Tregs 在后续活动性 UC 中的恢复，达到治疗后的缓解。活动期UC的EBV载量较高，EBV阳性亚组的Helios ⁺ FoxP3 ⁺ Tregs水平低于中重度活动期患者的EBV阴性亚组。最重要的是，我们发现 Helios ⁺ FoxP3 ⁺ Tregs 与 EBV 病毒载量显着负相关。

结论：Helios ⁺ FoxP3 ⁺ Tregs 可能在 UC 的疾病活动中起关键作用，并可能受到 EBV 感染的影响。