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

IF 10.9 1区医学 Q1 RHEUMATOLOGY Arthritis & Rheumatology Pub Date : 2024-12-25 DOI:10.1002/art.43096

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

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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.

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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Sjögren疾病的分层

最近，基于聚类分析，描述了Sjögren's病（SjD）患者的三种不同表型：B细胞活性低症状（BALS），高全身活性（HSA）和低全身活性高症状（LSAHS）。我们的目的是评估这些簇是否与不同的生物标志物和IFN信号的预后价值相关。方法：评估队列是一项为期20年的SjD患者前瞻性队列研究。比较以下生物标志物：IFN‐α2、IFN‐γ、CXCL10、CXCL13、BAFF、IL7、FLT3、CCL19和TNFRII。使用转录组学分析评估IFN特征。然后，我们比较了系统和症状的演变，以及新的免疫抑制剂处方和淋巴瘤的风险，根据三个集群的IFN特征。结果纳入395例患者（94%为女性，中位年龄53[43‐63]岁）。与LSAHS组相比，BALS组和HSA组的CXCL - 13、IL7和TNF - RII水平较高。IFN高信号主要出现在BALS组（57%，HSA组48%，LSAHS组38%）。这种IFN信号主要由I型IFN驱动，IFN‐α2水平较高。在BALS群中，IFN信号高与新的免疫抑制剂治疗的高风险相关(HR 9.38；95% ci 1.22‐72.16)。所有淋巴瘤都发生在具有高干扰素特征的患者中。结论三种SjD簇均表达不同的IFN特征，以及T细胞和B细胞活化标志物，证实了不同的病理生理机制。高IFN特征可以预测BALS集群的系统进化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Arthritis & Rheumatology RHEUMATOLOGY-

CiteScore

20.90

自引率

3.00%

发文量

371

期刊介绍： Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.