Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
23
09
2022
received:
28
02
2022
accepted:
06
10
2022
pmc-release:
01
04
2024
medline:
3
4
2023
pubmed:
26
10
2022
entrez:
25
10
2022
Statut:
ppublish
Résumé
Patients with diffuse cutaneous systemic sclerosis (dcSSc) display a complex clinical phenotype. Transcriptional profiling of whole blood or tissue from patients are affected by changes in cellular composition that drive gene expression and an inability to detect minority cell populations. We undertook this study to focus on the 2 main subtypes of circulating monocytes, classical monocytes (CMs) and nonclassical monocytes (NCMs) as a biomarker of SSc disease severity. SSc patients were recruited from the Prospective Registry for Early Systemic Sclerosis. Clinical data were collected, as well as peripheral blood for isolation of CMs and NCMs. Age-, sex-, and race-matched healthy volunteers were recruited as controls. Bulk macrophages were isolated from the skin in a separate cohort. All samples were assayed by RNA sequencing (RNA-seq). We used an unbiased approach to cluster patients into 3 groups (groups A-C) based on the transcriptional signatures of CMs relative to controls. Each group maintained their characteristic transcriptional signature in NCMs. Genes up-regulated in group C demonstrated the highest expression compared to the other groups in SSc skin macrophages, relative to controls. Patients from groups B and C exhibited worse lung function than group A, although there was no difference in SSc skin disease at baseline, relative to controls. We validated our approach by applying our group classifications to published bulk monocyte RNA-seq data from SSc patients, and we found that patients without skin disease were most likely to be classified as group A. We are the first to show that transcriptional signatures of CMs and NCMs can be used to unbiasedly stratify SSc patients and correlate with disease activity outcome measures.
Identifiants
pubmed: 36281773
doi: 10.1002/art.42380
pmc: PMC10165944
mid: NIHMS1843383
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-608Subventions
Organisme : NIAMS NIH HHS
ID : R21 AR074902
Pays : United States
Organisme : NIAMS NIH HHS
ID : K24 AR063120
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073270
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001424
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR075423
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135964
Pays : United States
Organisme : NIH HHS
ID : S10 OD026814
Pays : United States
Organisme : CSRD VA
ID : I01 CX001777
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134375
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK117824
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152677
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR064313
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147575
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR007611
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR072579
Pays : United States
Organisme : NIAMS NIH HHS
ID : R56 AR078211
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073284
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI163742
Pays : United States
Informations de copyright
© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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