Immunological profiling of patients with ulcerative colitis leads to identification of two inflammatory conditions and CD1a as a disease marker.
Immunological profiling of patients with ulcerative colitis leads to identification of two inflammatory conditions and CD1a as a disease marker.
复制标题
DOI：
10.1186/s12967-016-1048-9
复制
发表时间：
2016-11-03
影响因子：
7.4
通讯作者：
Gropp R
中科院分区：
文献类型：
--
作者：
Föhlinger M;Palamides P;Mansmann U;Beigel F;Siebeck M;Gropp R
了解溃疡性结肠炎（UC）病理表现发展机制的传统方法主要依赖于鉴定某些细胞类型和细胞因子，然后验证它们在体外和体内的作用。鉴于UC中的高度动态过程，需要免疫细胞、上皮细胞、内皮细胞、肌肉细胞和纤维细胞的串扰，这种方法可能会忽略个体不同炎症反应的时间和空间连接性。我们采取了一种更全面的方法，据此我们设计了流式细胞术分析和ELISA面板，并确定了UC患者与非UC供体相比的免疫学特征。该组由B细胞、T细胞、巨噬细胞、单核细胞、NK和NK T细胞及其亚型、细胞因子TGF β 1和HGF、趋化因子TARC和骨膜蛋白组成。从41名UC患者和30名非UC供体中采集血液。对分离的PBMC进行流式细胞术分析，并通过ELISA分析血清。数据进行聚类分析和相关分析。为了证实鉴定的细胞反映了UC患者结肠中的炎症状况，从UC患者的结肠中分离白细胞并进行相同的流式细胞术分析。免疫学分析后进行聚类和相关性分析导致鉴定两种炎性病症：“急性”病症，其特征在于适应性免疫细胞如浆细胞、表达TSLPR的CD 11b+巨噬细胞、表达CD 64和CCR 2的CD 14+单核细胞、HGF和TARC，以及“重塑”病症，其特征在于NK T细胞和表达TLSPR的CD 14+单核细胞、TGF β 1和骨膜蛋白。ROC分析确定TARC和TGF β 1是区分这两种情况的高潜力生物标志物（Δ = −6687.72 ng/ml; p = 1 E −04; AUC = 0.87）。此外，CD 1a + CD 11b+巨噬细胞（Δ = 17.73%CD1a + CD 11b +; p = 5E−04; AUC = 0.86）和CD 1a + CD 14+单核细胞（Δ = 20.35; p = 0.02，AUC = 0.75）被确定为具有区分UC和非UC供体的高潜力的标志物。与非UC对照样本相比，发现UC患者炎症结肠中的CD 1a + CD 11b+巨噬细胞和NK T细胞显著增加（p = 0.02）。UC患者的免疫学分析可能会提高我们对疾病个体表现和阶段的病理学基础的理解。这可能导致开发适应个人需求和疾病不同阶段的新型诊断和治疗干预措施。此外，这可能导致临床试验的患者分层。本文的在线版本（doi：10.1186/s12967-016-1048-9）包含补充材料，可供授权用户使用。
Conventional approaches to understand mechanisms underlying the development of pathological manifestations in ulcerative colitis (UC) mostly rely on identification of certain cell types and cytokines followed by verification of their roles in vitro and in vivo. In light of the highly dynamic processes in UC, requiring the cross talk of immune cells, epithelial-, endothelial-, muscle cells and fibrocytes, this approach might neglect temporal and spatial connectivity of individually differing inflammatory responses. We undertook a more holistic approach whereby we designed a flow cytometric analysis- and ELISA panel and determined the immunological profiles of UC patients in comparison to Non UC donors. This panel consisted of B-cells, T-cells, macrophages, monocytes, NK- and NK T-cells and subtypes thereof, the cytokines TGFß1 and HGF, the chemokine TARC and periostin. Blood was collected from 41 UC patients and 30 non-UC donors. Isolated PBMC were subjected to flow cytometric analysis and sera were analyzed by ELISA. Data were analysed by cluster- and correlation analysis. To corroborate that the identified cells reflected the inflammatory condition in the colon of UC patients, leucocytes were isolated from colons of UC patients and subjected to the same flow cytometric analysis. Immunological profiling followed by cluster- and correlation analysis led to the identification of two inflammatory conditions: An ‘acute’ condition characterized by adaptive immune cells as plasma cells, TSLPR expressing CD11b+ macrophages, CD64 and CCR2 expressing CD14+ monocytes, HGF and TARC and a ‘remodeling’ condition signified by NK T-cells and TLSPR expressing CD14+ monocytes, TGFß1 and periostin. ROC analysis identified TARC and TGFß1 as biological markers with high potential to discriminate between these two conditions (Δ = −6687.72 ng/ml; p = 1E−04; AUC = 0.87). In addition, CD1a+ CD11b+ macrophages (Δ = 17.73% CD1a+ CD11b+; p = 5E−04; AUC = 0.86) and CD1a+ CD14+ monocytes (Δ = 20.35; p = 0.02, AUC = 0.75) were identified as markers with high potential to discriminate between UC and Non UC donors. CD1a+ CD11b+ macrophages and NK T-cells were found to be significantly increased in inflamed colons of UC patients as compared to non-UC control samples (p = 0.02). Immunological profiling of UC patients might improve our understanding of the pathology underlying individual manifestations and phases of the disease. This might lead to the development of novel diagnostics and therapeutic interventions adapted to individual needs and different phases of the disease. In addition, it might result in stratification of patients for clinical trials. The online version of this article (doi:10.1186/s12967-016-1048-9) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
32.4
作者：
Basu R;O'Quinn DB;Silberger DJ;Schoeb TR;Fouser L;Ouyang W;Hatton RD;Weaver CT
通讯作者：
Weaver CT
DOI：
10.1073/pnas.192162899
发表时间：
2002-10-01
影响因子：
11.1
作者：
Lehmann, J;Huehn, J;Hamann, A
通讯作者：
Hamann, A
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1084/jem.20141505
发表时间：
2015-02-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bourgeois EA;Subramaniam S;Cheng TY;De Jong A;Layre E;Ly D;Salimi M;Legaspi A;Modlin RL;Salio M;Cerundolo V;Moody DB;Ogg G
通讯作者：
Ogg G