Longitudinal Global Transcriptomic Profiling of Preclinical Systemic Sclerosis Reveals Molecular Changes Associated With Disease Progression

Authors

Chiara Bellocchi
Lorenzo Beretta
Xuan Wang
Marka A Lyons
Maurizio Marchini
Maurizio Lorini
Vincenzo Carbonelli
Nicola Montano
Shervin Assassi

Language

English

Publication Date

4-3-2023

Journal

Rheumatology

DOI

10.1093/rheumatology/keac492

PMID

36040182

PMCID

PMC10072882

PubMedCentral® Posted Date

8-30-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Objective: To investigate peripheral blood cell (PBCs) global gene expression profile of SSc at its preclinical stage (PreSSc) and to characterize the molecular changes associated with progression to a definite disease over time.

Material and methods: Clinical data and PBCs of 33 participants with PreSSc and 16 healthy controls (HCs) were collected at baseline and follow-up (mean 4.2 years). Global gene expression profiling was conducted by RNA sequencing and a modular analysis was performed.

Results: Comparison of baseline PreSSc to HCs revealed 2889 differentially expressed genes. Interferon signalling was the only activated pathway among top over-represented pathways. Moreover, 10 modules were significantly decreased in PreSSc samples (related to lymphoid lineage, cytotoxic/NK cell, and erythropoiesis) in comparison to HCs. At follow-up, 14 subjects (42.4%) presented signs of progression (evolving PreSSc) and 19 remained in stable preclinical stage (stable PreSSc). Progression was not associated with baseline clinical features or baseline PBC transcript modules. At follow-up stable PreSSc normalized their down-regulated cytotoxic/NK cell and protein synthesis modules while evolving PreSSc kept a down-regulation of cytotoxic/NK cell and protein synthesis modules. Transcript level changes of follow-up vs baseline in stable PreSSc vs evolving PreSSc showed 549 differentially expressed transcripts (336 up and 213 down) with upregulation of the EIF2 Signalling pathway.

Conclusions: Participants with PreSSc had a distinct gene expression profile indicating that molecular differences at a transcriptomic level are already present in the preclinical stages of SSc. Furthermore, a reduced NK signature in PBCs was related to SSc progression over time.

Keywords

Humans, Transcriptome, Gene Expression Profiling, Scleroderma, Systemic, Up-Regulation, Disease Progression, preclinical SSc, gene expression, modular analysis, disease progression

Published Open-Access

yes

Recommended Citation

Bellocchi, Chiara; Beretta, Lorenzo; Wang, Xuan; et al., "Longitudinal Global Transcriptomic Profiling of Preclinical Systemic Sclerosis Reveals Molecular Changes Associated With Disease Progression" (2023). Faculty, Staff and Student Publications. 5307.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5307