Single-cell analysis reveals key differences between early-stage and late-stage systemic sclerosis skin across autoantibody subgroups.
Ann Rheum Dis
; 82(12): 1568-1579, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37580109
ABSTRACT
OBJECTIVES:
The severity of skin involvement in diffuse cutaneous systemic sclerosis (dcSSc) depends on stage of disease and differs between anti-RNA-polymerase III (ARA) and anti-topoisomerase antibody (ATA) subsets. We have investigated cellular differences in well-characterised dcSSc patients compared with healthy controls (HCs).METHODS:
We performed single-cell RNA sequencing on 4 mm skin biopsy samples from 12 patients with dcSSc and HCs (n=3) using droplet-based sequencing (10× genomics). Patients were well characterised by stage (>5 or <5 years disease duration) and autoantibody (ATA+ or ARA+). Analysis of whole skin cell subsets and fibroblast subpopulations across stage and ANA subgroup were used to interpret potential cellular differences anchored by these subgroups.RESULTS:
Fifteen forearm skin biopsies were analysed. There was a clear separation of SSc samples, by disease, stage and antibody, for all cells and fibroblast subclusters. Further analysis revealed differing cell cluster gene expression profiles between ATA+ and ARA+ patients. Cell-to-cell interaction suggest differing interactions between early and late stages of disease and autoantibody. TGFß response was mainly seen in fibroblasts and smooth muscle cells in early ATA+dcSSc skin samples, whereas in early ARA+dcSSc patient skin samples, the responding cells were endothelial, reflect broader differences between clinical phenotypes and distinct skin score trajectories across autoantibody subgroups of dcSSc.CONCLUSIONS:
We have identified cellular differences between the two main autoantibody subsets in dcSSc (ARA+ and ATA+). These differences reinforce the importance of considering autoantibody and stage of disease in management and trial design in SSc.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
/
Esclerodermia Difusa
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article