蕈样肉芽肿和塞扎里综合征患者的预测性和预后生物标志物（BIO-MUSE）：一项转化研究方案

Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE): Protocol for a Translational Study.

作者信息

Belfrage Emma, Ek Sara, Johansson Åsa, Brauner Hanna, Sonesson Andreas, Drott Kristina

机构信息

Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.

Department of Immunotechnology, Faculty of Engineering, Lund University, Lund, Sweden.

出版信息

JMIR Res Protoc. 2024 Apr 4;13:e55723. doi: 10.2196/55723.

DOI:10.2196/55723

PMID:38436589

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11027051/

Abstract

BACKGROUND

Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers.

OBJECTIVE

This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS.

METHODS

The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease.

RESULTS

Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted.

CONCLUSIONS

This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS.

TRIAL REGISTRATION

ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55723.

摘要

背景

皮肤T细胞淋巴瘤（CTCL）是一组罕见的淋巴瘤，主要累及皮肤。蕈样肉芽肿（MF）是CTCL最常见的形式，而 Sézary 综合征（SS）则较为少见。早期阶段（IA-IIA）预后良好，而晚期阶段（IIB-IVB）预后较差。约25%的疾病早期患者会进展为晚期。CTCL中恶性皮肤浸润性T细胞伴有非恶性T细胞和其他免疫细胞浸润，这些细胞会产生调节炎症的细胞因子。晚期常发生皮肤感染，通常由金黄色葡萄球菌引起，可导致败血症和死亡。据报道，金黄色葡萄球菌也会促进疾病进展。既往报道表明，CTCL中细胞因子产生从Th1向Th2转变，且皮肤屏障功能存在障碍。治疗反应高度可变且往往不可预测，因此需要新的预测和预后生物标志物。

目的

这项前瞻性转化研究旨在识别MF和SS患者血液和皮肤中的预后生物标志物。

方法

MF和SS患者的预测与预后生物标志物（BIO-MUSE）研究旨在招募120例成年MF或SS患者以及20名健康志愿者作为对照组。治疗将按照临床常规进行。每位患者每3个月进行一次采样，持续3年。对血液样本进行乳酸脱氢酶、免疫球蛋白E、白细胞介素、胸腺和活化调节趋化因子以及淋巴细胞亚群分析。将通过数字空间分析和单细胞RNA测序研究淋巴瘤微环境。进行微生物采样和皮肤屏障功能分析。评估生活质量参数。结果将根据疾病阶段进行评估。