Novel endotypes of antisynthetase syndrome identified independent of anti-aminoacyl transfer RNA synthetase antibody specificity that improve prognostic stratification.
Ann Rheum Dis
; 83(6): 775-786, 2024 May 15.
Article
in En
| MEDLINE
| ID: mdl-38395605
ABSTRACT
OBJECTIVES:
To systemically analyse the heterogeneity in the clinical manifestations and prognoses of patients with antisynthetase syndrome (ASS) and evaluate the transcriptional signatures related to different clinical phenotypes.METHODS:
A total of 701 patients with ASS were retrospectively enrolled. The clinical presentation and prognosis were assessed in association with four anti-aminoacyl transfer RNA synthetase (ARS) antibodies anti-Jo1, anti-PL7, anti-PL12 and anti-EJ. Unsupervised machine learning was performed for patient clustering independent of anti-ARS antibodies. Transcriptome sequencing was conducted in clustered ASS patients and healthy controls.RESULTS:
Patients with four different anti-ARS antibody subtypes demonstrated no significant differences in the incidence of rapidly progressive interstitial lung disease (RP-ILD) or prognoses. Unsupervised machine learning, independent of anti-ARS specificity, identified three endotypes with distinct clinical features and outcomes. Endotype 1 (RP-ILD cluster, 23.7%) was characterised by a high incidence of RP-ILD and a high mortality rate. Endotype 2 (dermatomyositis (DM)-like cluster, 14.5%) corresponded to patients with DM-like skin and muscle symptoms with an intermediate prognosis. Endotype 3 (arthritis cluster, 61.8%) was characterised by arthritis and mechanic's hands, with a good prognosis. Transcriptome sequencing revealed that the different endotypes had distinct gene signatures and biological processes.CONCLUSIONS:
Anti-ARS antibodies were not significant in stratifying ASS patients into subgroups with greater homogeneity in RP-ILD and prognoses. Novel ASS endotypes were identified independent of anti-ARS specificity and differed in clinical outcomes and transcriptional signatures, providing new insights into the pathogenesis of ASS.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoantibodies
/
Lung Diseases, Interstitial
/
Amino Acyl-tRNA Synthetases
/
Myositis
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Ann Rheum Dis
Year:
2024
Type:
Article