Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Clin Exp Immunol. 2024 Jun 20;217(1):78-88. doi: 10.1093/cei/uxae027.
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.
虽然肛周克罗恩病（PCD）与炎症加剧高度相关，但区分有肛周病变病史的患者的分子基础和免疫学特征仍不清楚。本文旨在定义与 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。采集血样检测血浆细胞因子和脂多糖（LPS）。通过流式细胞术对外周血单核细胞（PBMC）进行表型分析。用 LPS 或抗 CD3/抗 CD28 抗体刺激白细胞。我们的结果表明，CD 患者的血浆白细胞介素（IL）-6 和 LPS 增加。然而，他们的 PBMC 以 IL-6 产生减少为特征，而有 PCD 病史的患者产生更高水平的 IL-6、IL-8 和干扰素-γ，同时 TNF 减少。CD 患者的 FoxP3 和细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）调节标记物增加，尽管 PCD 患者的 CTLA-4 表达显著降低。CTLA-4 以及 IL-6 和 TNF 的反应能够将 PCD 患者与没有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 患者中表现出独特的表达模式，无论疾病活动如何。这些发现阐明了与肛周表现发展相关的一些机制，可能对疾病管理产生重大影响。
