P141 Anti-nucleolar antibody associations in systemic sclerosis-associated interstitial lung disease by disease subset

Anti-nuclear antibody (ANA) assessment plays a key role in the diagnosis, clinical stratification and prognostic evaluation of systemic sclerosis (SSc) patients. Hallmark SSc antibodies like anti-topoisomerase (ATA) have established association with interstitial lung disease (ILD) and are a useful tool to evaluate risk and inform clinical management. Fewer studies have evaluated the less common nucleolar antibodies (ANoA) including anti-U3 RNP (fibrillarin), anti-Th/To, and PmScl which also carry associations with SSc. In this analysis, we analysed clinical associations of ANoA in a well characterised SSc cohort.

Retrospective analysis of 246 SSc patients from a large tertiary centre with a positive ANoA pattern on serum analysis between 2019-2024 was undertaken. Primary ANA pattern and antigen presence was identified by indirect immunofluorescence (IIF) and line immunoblot assay (LIA) respectively. ANoA were analysed with respect to SSc subsets and clinical characteristics by organ involvement. Statistical analysis of ILD association in the Th/To and ENA negative antigen subgroups was performed by Fisher’s exact test and Koopman’s asymptotic score to calculate relative risk and confidence interval respectively.

Baseline characteristics of the SSc patients and presence of antigen reactivity including U3RNP, Th/To, PmScl, Ro 52, ENA negative as well as known hallmark ATA and ARA antibodies were collected (see table).

58% had the diffuse SSc subset. Average time since onset of SSc was 11 years. 37% (92/246) of the ANoA cohort had ILD. Amongst them, 11/92 (12%) were ENA negative. 11/45 (24%) of the ENA-negative group had ILD. The relative risk of ILD in the ANoA with ENA-negative group compared to ANoA with any antigen group was 0.57 (95% CI 0.3266 to 0.9384); p value 0.0275.

Additionally, Th/To was positive in 15/246 ANoA samples and a third (5/15) had ILD.

Our analysis further highlights the heterogeneity across SSc subtypes by the less widely studied ANoA and demonstrates statistically significant relative risk of ILD in the ANoA-positive but ENA-negative subgroup. There may be a role for early screening for ILD in this cohort of SSc patients; however, future prospective studies in larger cohorts and long term follow up are needed.

M. Kanitkar: None. C.P. Denton: None. V.H. Ong: None.