Antibodies may predict ILD progression in SSc patients

The presence of certain autoantibodies in patients with systemic sclerosis (SSc) is predictive of interstitial lung disease (ILD) progression, suggests a Singapore study.

“We ... identified that anti-La was associated with ILD progression within 1 and 3 years and anti-Scl-70 was associated with ILD progression within 5 years,” the researchers said. “This knowledge is helpful for risk stratification in the management of SSc-ILD and is potentially informative for cohort enrichment strategies in treatment trials of SSc-ILD.”

A total of 124 SSc patients with ILD diagnosed by high-resolution computed tomography were included in this prospective, multicentre study conducted from January 2008 to February 2021 in Singapore. The researchers performed multivariable logistic and Cox regression analyses, adjusting for malignancy and treatment, to identify the independent risk factors of ILD progression.

ILD progression was characterized by forced vital capacity (FVC) decline ≥10 percent predicted or FVC decline 5 percent to 9 percent predicted, with diffusing lung capacity of carbon monoxide decline ≥15 percent from the time of ILD diagnosis.

Of the participants, 47.6 percent had limited cutaneous SSC, 33.9 percent had diffuse SSC, and 18.5 percent had SSc-overlap. ILD progression occurred in 6 percent of patients within 1 year, 15 percent within 3 years, and 23 percent within 5 years. [Singapore Med J 2026;67:37-45]

Following adjustments for treatment and malignancy, anti-La was found to have a significant association with ILD progression within 1 (odds ratio [OR], 6.94, 95 percent confidence interval [CI], 1.14—42.2; p=0.04) and 3 years (OR, 5.98, 95 percent CI, 1.31—27.4; p=0.02). Anti-Scl-70 also significantly correlated with ILD progression within 5 years (OR, 2.54, 95 percent CI, 1.05—6.12; p=0.04).

Furthermore, in the analysis of time to ILD progression as an outcome, anti-La still showed a robust association with an increased risk of ILD progression (hazard ratio, 3.47, 95 percent CI, 1.18—10.2; p=0.02). Specifically, time to progression was 1.4 years in patients with anti-La vs 6.9 years in those without (p=0.02) and 4.7 years in patients with anti-Scl-70 vs 8.9 years in those without (p=0.12).

Antibodies

Previous studies have shown a link between anti-La antibodies and Sjogren’s syndrome, an autoimmune disorder that affects the exocrine gland. Furthermore, the La protein functions as a transcription termination factor of RNA polymerase III transcript. [Autoimmun Rev 2011;10:123-125]

“Although the number of patients with anti-La antibodies [in the current study (n=8, 6.5 percent)] was relatively small and the findings might have been due to chance alone, this is an interesting observation that warrants further investigation,” the researchers said.

On the other hand, anti-Scl-70 antibodies have been shown to have robust associations with ILD and diffuse cutaneous SSc in an earlier study. [Respir Res 2019;20:13]

When the anti-Scl-70 antibodies bind to DNA topoisomerase, it potentially triggers an inflammation response and contributes to the activation of fibroblasts, according to a previous study. [J Scleroderma Relat Disord 2020;5:103-129]

“The identification of anti-Scl-70 as a predictor of ILD progression during the 5-year follow-up in our cohort is important as it helps to stratify the patients who are at high risk of progression and would benefit from early treatment,” the researchers said. 

“This would lend support to proposed expert consensus recommendations to initiate treatment for ILD in high-risk patients who are asymptomatic and have preserved FVC >80 percent predicted,” they added. [Respir Res 2023;24:6]