Clinical and molecular characterization of ILD in patients with overlapping ASyS and SjD: a retrospective...

Interstitial lung disease (ILD) is a frequent complication in both anti-synthetase syndrome (ASyS) and primary Sjögren's disease (pSjD), but the clinical and molecular phenotype of patients with overlapping ASyS and pSjD (ASyS-SjD) remains poorly defined. This study aimed to characterize the clinical, serological, radiological and transcriptomic features of ASyS-SjD patients with ILD, and to determine whether this overlap represents a distinct disease entity.

We retrospectively analysed 131 ASyS, 78 pSjD and 42 ASyS-SjD patients from the First Affiliated Hospital of Nanjing Medical University between June 2020 and June 2023. Clinical features, laboratory findings, pulmonary function and HRCT patterns were compared. RNA sequencing was performed on peripheral blood mononuclear cells from eight ASyS, nine pSjD, 10 ASyS-SjD patients and 10 controls.

ASyS-SjD patients had earlier ILD onset (10.0 vs 67.5 months, P < 0.001), more RP-ILD (16.7% vs 3.9%, P = 0.015) and worse pulmonary function than pSjD patients (FEV1%: 63.5% vs 76.6%, P = 0.010; FVC%: 64.2% vs 77.0%, P = 0.024; DLCO%: 60.7% vs 72.6%, P = 0.046). HRCT showed predominantly NSIP in ASyS-SjD (75.6%), similar to ASyS, with rare LIP (2.4%). ILD characteristics between ASyS-SjD and ASyS were comparable. Transcriptomics revealed shared inflammation with ASyS plus unique profibrotic signalling in ASyS-SjD.

ASyS-SjD exhibits an ASyS-like clinical phenotype with additional profibrotic features, suggesting it may represent an overlap subtype rather than a coincidental coexistence. While ILD in ASyS-SjD appears more aggressive than in SjD, it is not clearly more severe than in ASyS.