Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn's disease.

IF 3.4 3区 医学 Q3 IMMUNOLOGY Clinical and experimental immunology Pub Date : 2024-06-20 DOI:10.1093/cei/uxae027
Murillo Duarte-Silva, Rogério Serafim Parra, Marley Ribeiro Feitosa, Viviani Nardini, Sandra Regina Maruyama, José Joaquim Ribeiro da Rocha, Omar Feres, Cristina Ribeiro de Barros Cardoso
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Abstract

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.

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白细胞功能障碍和 CTLA-4 表达减少与肛周克罗恩病有关
虽然肛周克罗恩病(PCD)与炎症加重高度相关,但区分肛周病变患者的分子基础和免疫学特征仍不清楚。本文旨在明确与 PCD 相关的免疫学特征。在这项横断面观察性研究中,我们招募了 20 名健康对照者和 39 名 CD 患者。采集血样用于检测血浆细胞因子和 LPS。用流式细胞仪对白细胞进行表型。用 LPS 或抗-CD3/抗-CD28 抗体刺激白细胞。结果显示,CD 患者的血浆 IL-6 和 LPS 增高。而有 PCD 病史的患者产生的 IL-6、IL-8 和 IFN-γ 较高,TNF 较低。CD患者的FoxP3和CTLA-4调节标志物增加,而PCD患者的CTLA-4表达明显减少。CTLA-4以及IL-6和TNF反应能够将PCD患者与未出现肛周并发症的患者区分开来。总之,IL-6、TNF 和 CTLA-4 在有 PCD 病史的 CD 患者中表现出不同的表达模式,与疾病活动无关。这些发现阐明了肛周表现的一些发病机制,可能会对疾病的治疗产生重大影响。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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