基于症状、临床和常规生物学数据，不同的病理生理途径支持干燥综合征的分层。

Distinct Pathophysiologic Pathways Support Stratification of Sjögren's Disease Based on Symptoms, Clinical, and Routine Biological Data.

作者信息

Nguyen Yann, Beydon Maxime, Gottenberg Jacques-Eric, Morel Jacques, Perdriger Aleth, Dernis Emmanuelle, Cornec Divi, Devauchelle-Pensec Valérie, Sène Damien, Dieudé Philippe, Couderc Marion, Fauchais Anne-Laure, Larroche Claire, Vittecoq Olivier, Salliot Carine, Hachulla Eric, Le Guern Véronique, Mariette Xavier, Seror Raphaèle, Nocturne Gaëtane

机构信息

Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Saclay, Le Kremlin-Bicêtre, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, Université Paris Cité, Clichy, Centre de Recherche en Epidémiologie et Statistiques, INSERM UMR 1153, Université Paris Cité, Paris, France.

出版信息

Arthritis Rheumatol. 2025 Jul;77(7):876-883. doi: 10.1002/art.43096. Epub 2025 Jan 27.

DOI:10.1002/art.43096

PMID:39721742

Abstract

OBJECTIVE

Recently, three distinct phenotypes of patients with Sjögren disease (SjD) have been described based on cluster analysis: B cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS). We aimed to assess whether these clusters were associated with distinct biomarkers and the prognostic value of interferon (IFN) signature.

METHODS

The Assessment of Systemic Signs and Evolution in Sjögren's Syndrome cohort is a 20-year prospective cohort of patients with SjD. The following biomarkers were compared: IFN-α2, IFN-γ, CXCL10, CXCL13, BAFF, interleukin (IL)-7, fms-like tyrosine kinase 3 ligand, CCL19, and tumor necrosis factor receptor 2 (TNF-RII). IFN signature was assessed using transcriptomic analysis. We then compared systemic and symptomatic evolution, and the risk of new immunosuppressant prescription and of lymphoma, according to the IFN signature across the three clusters.

RESULTS

A total of 395 patients (94% female, median age 53 [interquartile range 43-63] years) were included. Higher levels of CXCL13, IL-7, and TNF-RII were found in the BALS and HSA clusters compared with the LSAHS cluster. A high IFN signature was mainly found in the BALS cluster (57%, vs 48% and 38% in the HSA and LSAHS clusters, respectively). This IFN signature was mainly driven by type I IFN, with higher levels of IFN-α2. In the BALS cluster, a high IFN signature was associated with a higher risk of new immunosuppressant treatment (hazard ratio 9.38; 95% confidence interval 1.22-72.16). All lymphoma occurred in patients with high IFN signature.

CONCLUSION

The three SjD clusters displayed distinct expressions of IFN signature and markers of T and B cell activation, confirming distinct pathophysiologic mechanisms. High IFN signature could predict systemic evolution in the BALS cluster.

摘要

目的

最近，基于聚类分析描述了干燥综合征（SjD）患者的三种不同表型：低症状的B细胞活跃型（BALS）、高全身活动型（HSA）和高症状的低全身活动型（LSAHS）。我们旨在评估这些聚类是否与不同的生物标志物以及干扰素（IFN）特征的预后价值相关。

方法

干燥综合征全身症状评估与疾病进展队列研究是一项对SjD患者进行的为期20年的前瞻性队列研究。比较了以下生物标志物：IFN-α2、IFN-γ、CXCL10、CXCL13、BAFF、白细胞介素（IL）-7、fms样酪氨酸激酶3配体、CCL19和肿瘤坏死因子受体2（TNF-RII）。使用转录组分析评估IFN特征。然后，我们根据三个聚类中的IFN特征比较了全身和症状进展，以及新的免疫抑制剂处方和淋巴瘤的风险。

结果

共纳入395例患者（94%为女性，中位年龄53岁[四分位间距43 - 63岁]）。与LSAHS聚类相比，BALS和HSA聚类中CXCL13、IL-7和TNF-RII水平更高。高IFN特征主要见于BALS聚类（57%，而HSA和LSAHS聚类中分别为48%和38%）。这种IFN特征主要由I型IFN驱动，IFN-α2水平更高。在BALS聚类中，高IFN特征与新的免疫抑制剂治疗风险较高相关（风险比9.38；95%置信区间1.22 - 72.16）。所有淋巴瘤均发生在具有高IFN特征的患者中。