Unveiling the clinical spectrum of ACA-positive SSC-ILD: not as benign as expected

ACA-positive interstitial lung disease (ILD) in SSc is traditionally considered less aggressive than anti-topo I antibody (ATA)-positive ILD. However, its clinical profile and prognosis remain poorly defined. We aimed to characterize ACA-associated SSc-ILD and compare it with other serological subsets.

Multicentre cross-sectional observational study including 76 ACA-positive SSc-ILD patients, compared with ATA-positive (n = 54) and ACA/ATA-negative (n = 147) groups.

ACA-positive patients developed ILD earlier than ATA-positive and ACA/ATA-negative individuals (2.5 vs 5.6 and 3.5 years; P = 0.389). Compared with the other groups, they had higher pFVC (96.3% vs 83.5% and 86.9%; P = 0.013), lower pFEV1/pFVC ratio (91.6% vs 99.2% and 98.8%; P = 0.004) and better functional capacity, with fewer NYHA class III-IV patients (14.5% vs 42.6% and 32%; P = 0.017). They also showed lower pKCO (71.7% vs 85.1% and 77.4%; P = 0.008) and higher pFVC/pDLCO ratio (1.8 vs 1.4 and 1.5; P = 0.016), suggesting indolent microvascular damage and increased pulmonary vascular resistance. Differences in pDLCO were not significant (60.2% vs 60.9% and 65.7%; P = 0.769). ILD worsening (ATS criteria) occurred in 14.5% of ACA-positive patients. No significant differences were found in antifibrotic indication or advanced interventions. However, 2.6% underwent lung transplantation (0% ATA-positive, 1.4% ACA/ATA-negative) and 2.6% received autologous haematopoietic stem cell transplantation (0% and 3.4%, respectively). Overall survival analysis revealed no significant differences across the three groups (P = 0.164), although ACA/ATA-negative patients showed better survival than ACA-positive patients (P = 0.041; HR 0.498, P = 0.045).

ACA-positive SSc-ILD does not seem to have a more favourable long-term prognosis compared with other serological subsets.