Severe lung involvement in SSc linked to anti-Ro/SSA antibodies

Recent findings from a study based on the EUSTAR database highlight that anti-Ro/SSA antibodies are strongly associated with severe lung involvement. These findings underscore the potential of anti-Ro/SSA antibodies as valuable biomarkers for better risk assessment and management in systemic sclerosis (SSc).

Anti-Ro/SSA antibodies have been associated with interstitial lung disease (ILD) in different connective tissue diseases [1,2]. Yet, despite better stratification of SSc patients with SSc-specific antibodies, individual prognosis remains unpredictable [3]. Thus, further exploration of SSc non-specific antibodies is crucial to enhance risk assessment and refine management strategies for SSc patients.

Dr Blaž Burja (University Hospital Zurich, Switzerland) and his team evaluated the prevalence of anti-Ro/SSA antibodies in patients with SSc and the association of these antibodies with disease phenotype and clinical outcomes, focussing on lung involvement [4]. “We examined the largest available cohort of established SSc patients selected from the EUSTAR database together with available data on anti-Ro/SSA antibodies,” Dr Burja explained.

The team assessed the presence of lung fibrosis using high-resolution computer tomography (HRCT) over a median of 2.7 years of follow-up, employing multivariable logistic regression to identify associated factors. In addition, the impact of anti-Ro/SSA antibodies on lung function (i.e. functional vital capacity [FVC] and diffusing capacity for carbon monoxide [DLCO]) in these patients was calculated.

Out of 4,421 patients with SSc meeting the 2013 criteria in the EUSTAR database, 661 (15.2%) tested positive for anti-Ro/SSA antibodies. These antibodies were significantly linked (P<0.001) with anti-SSB, anti-U1RNP antibodies, and rheumatoid factor. Patients with anti-Ro/SSA antibodies showed higher rates of muscular involvement (18% vs 12.5%; P<0.001) and ILD (56.2% vs 47.8%; P=0.001) compared with those without. The presence of anti-Ro/SSA antibodies independently predicted the presence of lung fibrosis during follow-up (OR 1.24; 95% CI 1.07–1.44; P=0.006; see Figure) and was associated with lower DLCO (regression coefficient -1.93; 95% CI -3.83 to 0.02; P=0.049) in affected patients. Also, it revealed a trend for lower FVC in these individuals (P=0.082). However, anti-Ro/SSA antibodies did not predict the progression of lung fibrosis or mortality over time.

Figure: Anti-Ro/SSA antibodies are a risk factor for ILD [4]



ANA, antinuclear antibodies; CRP, C-reactive protein; GI, gastrointestinal; ILD, interstitial lung disease; LVEF, left ventricular ejection fraction; SSc, systemic sclerosis.

Multivariable analysis from 14,066 visits; adjusted for known risk factors for ILD.

“Overall, the presence of anti-Ro/SSA antibodies in 15.2% of the SSc cohort signifies an independent risk factor for lung fibrosis development,” Dr Burja concluded. Therefore, integrating the assessment of anti-Ro/SSA antibodies into routine clinical practice is advisable to identify individuals at higher risk of ILD, particularly beneficial in settings without access to HRCT scans, where these antibodies can serve as crucial biomarkers for screening.

1. Wodkowsky M, et al. Clin Exp Rheum 2015;33 (Suppl. 91):S131-135.
2. Nagy A, et al. Front Pharmacol 2021;12:778649.
3. Elhai M, et al. Lancet Rheumatol 2022;4:E785-794.
4. Burja B, et al. Anti-Ro/SSA antibodies are predictive of a more severe lung involvement in patients with systemic sclerosis: a study from the EUSTAR database. OP0013, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 202429 July 2024