Background: Anti-centromere antibodies (ACA) are generally considered protective against the development of interstitial lung disease (ILD) in systemic sclerosis (SSc). However, ILD can still occur and progress in ACA-positive patients.

Objectives: To analyze the prevalence, clinical characteristics, risk of ILD progression, and prognosis of ILD-SSc ACA-positive patients.

Methods: We conducted a multicenter retrospective observational study involving 277 patients who fulfilled the 2013 ACR/EULAR classification criteria for SSc. All patients had ILD confirmed by thoracic HRCT. A comparative analysis was performed across three groups: ACA-positive, ATA-positive, and ACA/ATA-negative patients.

Results: The demographic and clinical characteristics of the study population are summarized in Table 1. Out of 277 patients, 76 (27.4%) were ACA-positive, 54 (19.5%) were ATA-positive, and 146 (53.1%) were ACA/ATA-negative. The comparative analysis of the three groups (see Table 2) indicates that ACA-positive patients exhibited a distinct ILD profile. Notably, these patients demonstrated better functional status, as reflected by their superior NYHA class (p=0.017), despite no significant differences in the 6-minute walking test (p=0.859) or mortality rates (p=0.196). The time from SSc onset to ILD diagnosis was comparable across groups (p=0.389), suggesting that ACA positivity does not significantly delay ILD onset. The predominant radiological pattern in all groups was NSIP, with no significant differences in other radiological patterns (p=0.403). Pulmonary function tests revealed that, at ILD diagnosis, ACA-positive patients had higher %FVC (p=0.013), FEV1/FVC ratio (p=0.004), %pDLCO (p=0.008), and FVC/DLCO ratio (p=0.016), indicating better preserved lung function compared to ATA-positive and ACA/ATA-negative patients. This likely explains the better clinical course observed in ACA-positive cases. Regarding treatment, ACA-positive patients were less frequently treated with mycophenolate mofetil (p=0.003), whereas the use of other therapies, including rituximab, cyclophosphamide, and nintedanib, showed no significant differences between groups. Notably, two ACA-positive patients (2.6%) required lung transplantation, and another two (2.6%) underwent autologous hematopoietic stem cell transplantation.

Conclusion: ACA-positive SSc-ILD represents a distinct phenotype, characterised by better preserved pulmonary function and less severe functional impairment compared to ATA-positive or ACA/ATA-negative ILD. However, ACA positivity does not ensure a benign disease course, as some patients may still experience severe progression, requiring advanced therapies, including lung or autologous stem cell transplantation.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.