There is little sound evidence for an independent prognostic value of ATA and ACA for mortality in SSc.

Disease duration at baseline should be taken into account in study designs, specifically because disease trajectories differ significantly between ACA and ATA patients.

Future studies are warranted in well described early SSc cohorts to determine the possible role of ATA and/or ACA as biomarkers for every day clinical management and trial enrichment.

Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) are the most prevalent systemic sclerosis (SSc) specific antibodies and are associated with distinct clinical phenotypes. This study reviews the prognostic potential of these autoantibodies for disease specific complications.

Literature searches of PubMed (MEDLINE), Embase, Web of Science and Cochrane Library were performed to identify longitudinal SSc-studies, reporting on the prognostic value of ATA and ACA for any aspect of survival or disease complications. After full text review, studies with <30 events of interest, <30 ACA positive and/or ATA positive patients, and with a moderate to high risk of bias (according to the QUIPS risk of bias tool) were excluded.

Of 872 retrieved articles, 43 fulfilled the inclusion criteria. The included studies showed great heterogeneity in baseline characteristics and study design: mean baseline disease duration varied from 1 to 12 years and follow-up duration ranged from 1 to 18.1 years. One of the 21 studies found that ATA has prognostic value for mortality. Five of the nineteen available studies observed higher survival rates for ACA positive patients. Future development of ILD was associated with ATA in four of the seven studies, whereas ACA was associated with lower risk of ILD development in three out of four studies. For other disease outcomes, data are scarce.

In conclusion, there is little sound evidence to support an independent prognostic value of ATA and ACA for mortality in SSc. ATA is associated with future ILD development, while ACA decreases the risk of ILD development. To determine the possible role of ATA and/or ACA as biomarkers for every day clinical management and trial enrichment, future studies are warranted in well described cohorts in early SSc.

© 2025 The Authors. Published by Elsevier Inc.