Objectives Systemic sclerosis (SSc) is a heterogeneous disease, complicating its management. Its complexity and the insufficiency of clinical manifestations alone to delineate homogeneous patient groups further challenge this task. However, autoantibodies could serve as relevant markers for the pathophysiological mechanisms driving the disease. Identifying specific immunological mechanisms based on patients’ serological statuses might facilitate a deeper understanding of the diversity of the disease. Methods A cohort of 206 patients with SSc enrolled in the PRECISESADS cross-sectional study was examined. Patients were stratified based on their anti-centromere (ACA) and anti-SCL70 (SCL70) antibody statuses. Comprehensive omics analyses including transcriptomic, flow cytometric, cytokine and metabolomic data were analysed to characterise the differences between these patient groups. Results Patients with SCL70 antibodies showed severe clinical features such as diffuse cutaneous sclerosis and pulmonary fibrosis and were biologically distinguished by unique transcriptomic profiles. They exhibit a pro-inflammatory and fibrotic signature associated with impaired tissue remodelling and increased carnitine metabolism. Conversely, ACA-positive patients exhibited an immunomodulation and tissue homeostasis signature and increased phospholipid metabolism. Conclusions Patients with SSc display varying biological profiles based on their serological status. The findings highlight the potential utility of serological status as a discriminating factor in disease severity and suggest its relevance in tailoring treatment strategies and future research directions.

Bénedicte Rouvière

Christelle Le Dantec

Eleonore Bettacchioli

Lorenzo Beretta

Nathan Foulquier

Celine Cao

Christophe Jamin

Jacques-Olivier Pers

Martin Kerick

Javier Martin

Marta Eugenia Alarcón-Riquelme

Claire de Moreuil

Divi Cornec

Sophie Hillion

Annals of the Rheumatic Diseases

风湿病年鉴 (ARD) 是一份国际同行评审期刊，致力于促进最高标准的科学交流和教育。它涵盖了风湿病学的所有方面，包括肌肉骨骼疾病、关节炎疾病和结缔组织疾病的谱系。 ARD 发表基础、临床和转化科学研究。鼓励简明的科学交流，并以同行评审的国际会议论文集为特色。教育论文包括最先进的评论、“如何”文章和教育案例，重点关注临床实践中面临的问题。该杂志于 1939 年首次出版，拥有权威的全球编辑委员会和不断增长的国际读者群。

The Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal dedicated to promoting the highest standards of scientific communication and education. It covers all aspects of rheumatology, including musculoskeletal disorders, arthritic diseases, and connective tissue diseases. ARD publishes basic, clinical, and translational scientific research, encouraging concise scientific communication and featuring peer-reviewed conference proceedings. Educational papers include cutting-edge reviews, 'how-to' articles, and educational cases, focusing on issues faced in clinical practice. Since its first publication in 1939, the journal has maintained a prestigious global editorial board and a growing international readership.

《Annals of the Rheumatic Diseases》（风湿病年鉴，ARD）是一份国际同行评审的学术期刊，旨在促进高标准的科学交流与教育。期刊涵盖风湿病学的各个方面，包括肌肉骨骼疾病、关节炎和结缔组织疾病等。ARD发表基础研究、临床研究和转化科学研究，鼓励简洁明了的科学交流，并定期刊登国际会议的同行评审论文。教育类论文包括前沿评论、实用指南和教育案例，重点关注临床实践中遇到的问题。该杂志自1939年创刊以来，拥有权威的全球编辑委员会和不断扩大的国际读者群。

Stratification according to autoantibody status in systemic sclerosis reveals distinct molecular signatures

根据系统性硬化症自身抗体状态的分层揭示不同的分子特征

Category	Quartile
医学	1
医学, 风湿病学	1

Stratification according to autoantibody status in systemic sclerosis reveals distinct molecular signatures

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