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.
Longitudinal global transcriptomic profiling of preclinical systemic sclerosis reveals molecular changes associated with disease progression / C. Bellocchi, L. Beretta, X. Wang, M. A Lyons, M. Marchini, M. Lorini, V. Carbonelli, N. Montano, S. Assassi. - In: RHEUMATOLOGY. - ISSN 1462-0324. - (2023). [Epub ahead of print] [10.1093/rheumatology/keac492]
Longitudinal global transcriptomic profiling of preclinical systemic sclerosis reveals molecular changes associated with disease progression
C. Bellocchi
Primo
;M. Marchini;M. Lorini;V. Carbonelli;N. Montano;
2023
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.File | Dimensione | Formato | |
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