Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity.
Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity.
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通过粘膜微环境和免疫检查点的免疫组织化学分析预测溃疡性结肠炎患者治疗中的类固醇需求：巨噬细胞和调节标记物在疾病严重程度中的作用。
DOI：
10.1111/pin.12794
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
T. Mine.
中科院分区：
文献类型：
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作者：
S.Tsuda;J. Carreras;Y. kikuchi;H.Nakae;M. Dekiden;J. Imai;K. Tsuruya;J. Nakamura;Y. Tsukune;T. Uchida;M. Matsushima;G. Roncador;T. Suzuki;N. Nakamura;T. Mine.
我们的目的是通过免疫组化表征溃疡性结肠炎（UC）的粘膜免疫微环境和免疫检查点与预后的相关性：诊断后2年内（SR）需要二线类固醇治疗。一系列72例病例包括56例UC、43例非SR（一线治疗5-阿萨）和13例SR、11例感染性结肠炎和5例正常结肠活检。正常粘膜的特征是低浸润，但高BTLA和TNFRSF 14。与正常人相比，UC的泛免疫标志物CD 3、CD 8、FOXP 3、PD-1、CD 68、CD 16、CD 163、PTX 3和CD 11 C增加，但BTLA降低（P< 0.05）;通过GSEA分析，在独立的UC基因表达数据集中发现了相当的结果（GSE 38713）。UC组CD 4、CD 8、PTX 3、CD 11 C高于感染组，BTLA低于感染组（P< 0.05）。与非SR相比，SR具有较低的FOXP 3 + T细胞（比值比= 0.114，P = 0.002）、PD-1（OR = 0.176，P = 0.002）和CD 163/CD 68 M2-比值（OR，0.019，P = 0.019），但较高的CD 68+泛巨噬细胞（OR = 6.034，P = 0.002）。Baron内镜和Geboes组织学疾病活动性评分较高也与SR相关。总之，UC的特征是泛免疫标志物增加、TNFRSF 14正常和BTLA低。SR增加了CD 68+泛巨噬细胞，但降低了FOXP 3 + TcP、PD-1和CD 163/CD 68 M2-巨噬细胞比率的免疫抑制剂。总之，免疫稳态机制的改变与UC发病机制和类固醇需求情况相关。
We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second‐line steroid‐therapy within the 2‐years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non‐SR (with first‐line treatment 5‐ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan‐immune‐markers of CD3, CD8, FOXP3, PD‐1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P< 0.05); by GSEA analysis comparable results were found in an independent UC gene‐expression‐data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P< 0.05). Compared to non‐SR, SR had lower FOXP3 + Tregs (Odds‐Ratio = 0.114,P= 0.002), PD‐1 (OR = 0.176,P= 0.002) and CD163/CD68 M2‐ratio (OR, 0.019,P= 0.019) but higher CD68 + pan‐macrophages (OR = 6.034,P= 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan‐immune‐markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan‐macrophages but lower immune inhibitors of FOXP3 + Tregs, PD‐1 and CD163/CD68 M2‐macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid‐requiring situation.