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Integrative Transcriptomic Analysis of Peripheral Blood Monocytes in Systemic Sclerosis and Shared Pathogenic Pathways in Autoimmune Diseases.
Chen, Shaoqi; Fan, Yu; Wu, Qiulin; Zhang, Guohong; Wang, Yukai; Li, Weiping; Yang, Shengli; Matucci-Cerinic, Marco; Furst, Daniel E.
Afiliación
  • Chen S; The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
  • Fan Y; Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China.
  • Wu Q; The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
  • Zhang G; Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China.
  • Wang Y; Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, Guangdong, China.
  • Li W; The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. Electronic address: wpli818@126.com.
  • Yang S; The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shanghai Academician Consulting and Academic Activities Center of Chinese Academy of Engineering, Shanghai, China. Electronic address: slyang@caeshc.com.cn.
  • Matucci-Cerinic M; Unit of Immunology, Rheumatology, Allergy and Rare diseases, San Raffaele Hospital, Milan, Italy.
  • Furst DE; Division of Rheumatology, School of Medicine, University of California at Los Angeles, California, USA.
Arch Med Res ; 56(1): 103072, 2024 Aug 28.
Article en En | MEDLINE | ID: mdl-39208548
ABSTRACT

BACKGROUND:

Systemic sclerosis (SSc) is an autoimmune disease (AD), that receives less attention compared to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS). This study aims to analyze transcriptional profiles and immune cell composition in peripheral blood mononuclear cells (PBMC) from SSc patients compared to other ADs.

METHODS:

RNA-seq data from 119 untreated patients (eight with SSc, 42 with RA, 41 with pSS, 28 with SLE) and 20 healthy controls were analyzed. Bioinformatics tools were employed to identify differentially expressed genes (DEGs), biological functions and immune cell profiles unique to SSc and shared with other ADs.

RESULTS:

1,148 DEGs were found in SSc, with upregulated genes associated with megakaryocyte processes and downregulated genes associated with neutrophil function and immune response. DEGs, including ALDH1A1 and MEGF9, were associated with neutropenia. Upregulated transcription factors (TFs) were linked to embryonic hematopoiesis and downregulated TFs were involved in leukocyte differentiation and immune regulation. Comparative analysis with other ADs revealed common pathogenic pathways, emphasizing megakaryocyte proliferation. Neutrophils count was significantly decreased in ADs (p < 0.001) compared to healthy controls. Comparative analysis highlighted common pathways, particularly in megakaryocyte proliferation, and unique genes (MEGF9, MMP8, and KRT family members) in SSc, suggesting roles in neutrophil function, skin integrity, and fibrosis.

CONCLUSIONS:

This study identifies dysregulated gene expression (KRT and MMP8) associated with neutrophil function and increased megakaryocytes in SSc, highlighting common patterns across autoimmune diseases. These findings offer new insights into the potential pathogenesis of SSc, and help to explore new targets for the treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Arch Med Res Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Arch Med Res Asunto de la revista: MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos