{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bellocchi C"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","Gruppo Italiano per la Lotta alla Sclerodermia GILS Bando Giovani Ricercatori","National Institutes of Health","NIAMS NIH HHS"],"pagination":["1662-1668"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10072882"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["62(4)"],"pubmed_abstract":["<h4>Objective</h4>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.<h4>Material and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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."],"journal":["Rheumatology (Oxford, England)"],"pubmed_title":["Longitudinal global transcriptomic profiling of preclinical systemic sclerosis reveals molecular changes associated with disease progression."],"pmcid":["PMC10072882"],"funding_grant_id":["R61 AR078078","R61AR078078","R56 AR078211","R56AR078211"],"pubmed_authors":["Lorini M","Bellocchi C","Beretta L","Lyons MA","Assassi S","Marchini M","Montano N","Wang X","Carbonelli V"],"additional_accession":[]},"is_claimable":false,"name":"Longitudinal global transcriptomic profiling of preclinical systemic sclerosis reveals molecular changes associated with disease progression.","description":"<h4>Objective</h4>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.<h4>Material and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2025-06-25T03:04:35.708Z","creation":"2025-04-05T14:02:26.175Z"},"accession":"S-EPMC10072882","cross_references":{"pubmed":["36040182"],"doi":["10.1093/rheumatology/keac492"]}}