A75-22 Serologic Autoantibodies and Telomere Length in Unclassifiable and Connective Tissue Disease-Related Interstitial Lung Disease

Rationale

Autoimmune disease and telomere shortening are both risk factors for interstitial lung disease (ILD). Even without a connective tissue disease related-ILD diagnosis (CTD-ILD), autoimmune features and serologies are highly prevalent amongst those with unclassifiable ILD (UILD). Whether the prevalence of genetic features such as telomere shortening differs between CTD-ILD and UILD is unknown.

Methods

We conducted a retrospective observational cohort study of patients evaluated at the Columbia University ILD clinic from 2019-2025. We abstracted medical records including clinical demographics, family history of pulmonary fibrosis, and autoimmune serologic testing (ANA, rheumatoid factor, anti-CCP, anti-dsDNA, anti-Smith, anti-SSA/SSB, anti-Scl-70, anti-centromere, anti-Jo-1, anti-RNP, or other myositis-specific antibodies). We performed qPCR leukocyte telomere length (LTL) measurements from banked biospecimens. We compared telomere length across diagnostic categories using ANOVA and Tukey’s test. We also compared family history of pulmonary fibrosis across ILD diagnoses using chi-squared test and logistic regression to determine adjusted odds of familial disease.

Results

In total, we included 119 patients with CTD-ILD and 109 patients with UILD. We stratified UILD patients by autoimmune features and serologies, including those meeting criteria for idiopathic pneumonia with autoimmune features (IPAF, n = 35), and those not meeting IPAF criteria with and without any positive serologic testing (seropositive UILD, n = 33, seronegative UILD, n = 41). LTL varied across diagnostic categories of CTD-ILD (mean age-adjusted LTL -0.05±0.25), IPAF (-0.13±0.25), seropositive UILD (-0.16±0.24), and seronegative UILD (-0.17±0.27) with significant between-group differences (ANOVA p = 0.01). Pair-wise Tukey’s test showed significantly shorter LTL in patients with seronegative UILD vs. CTD-ILD (adjusted p = 0.03). We also found overall differences in proportion of familial disease amongst all diagnostic categories (chi-squared p = 0.002). Amongst UILD patients, there was a significant difference in family history between IPAF patients (17% familial) and seronegative UILD (54% familial, chi-squared p = 0.007). Having a diagnosis of seronegative UILD was associated with higher adjusted odds of familial disease (OR 3.23 95% CI 1.66-22.4) compared to having a diagnosis of IPAF.

Conclusions

We find that UILD patients without apparent autoimmune features or serologies have shorter telomere lengths compared to CTD-ILD patients. Amongst patients with UILD, those with seronegative UILD have significantly more familial disease than those with IPAF.

This abstract is funded by: NIH