Abstract Rationale Anti-SS-A (Ro) antibodies are commonly associated with connective tissue diseases (CTDs) such as Sjögren’s, systemic lupus erythematosus, or myositis. However, some patients present with interstitial lung disease (ILD) and isolated SS-A positivity in the absence of clinical or other serologic evidence of CTD. The clinical significance and trajectory of this subset remain unclear. Methods We retrospectively reviewed CT chest reports and open-lung biopsy reports, and surveyed clinicians at our institutions who manage ILD patients. We found three patients with ILD and isolated SS-A positivity. All other rheumatologic serologies—including Antinuclear Antibodies, Rheumatoid Factor, Anti-Cyclic Citrullinated Peptide, Antineutrophil Cytoplasmic Antibodies, and myositis antibody panels—were negative. None had elevated Creatinine Kinase or aldolase. None met CTD classification criteria. Demographic, clinical, radiologic, and histopathologic data were summarized. Results Three patients with isolated anti-SS-A-positive interstitial lung disease (ILD) were identified, all lacking clinical or serologic evidence of connective tissue disease (CTD). The cohort included two females and one male, aged 56-72 years. Radiologic patterns included usual interstitial pneumonia (UIP) in one and nonspecific interstitial pneumonia (NSIP) in two, with one case showing overlapping organizing pneumonia (OP). Histopathology, available in two cases, showed autoimmune-related UIP and NSIP with chronic inflammation/fibrosis. Pulmonary function testing demonstrated moderate-to-severe restriction (FVC 1.62-1.8 L; 48-56% predicted; TLC 2.24-2.64 L; 39-57% predicted) and reduced diffusing capacity (DLCO 9.85-11.4 mL/min/mmHg; 52-57% predicted). Six-minute walk distance ranged from 400 ft to 1,400 ft. None developed extrapulmonary autoimmune manifestations or met CTD classification criteria during 9-36 months of follow-up. Clinical course ranged from stable to progressive fibrosing ILD. Conclusion Isolated SS-A positive IPAF may be an underrecognized phenotype within the autoimmune spectrum. The presence of histologic inflammation and varying disease behavior suggests an immune-mediated mechanism in our series. Recognizing this subgroup could help guide prognosis, biopsy interpretation, and long-term management. However, no studies have focused specifically on isolated anti-SSA antibody-positive phenotypes of IPAF. Further research is needed in this area. This abstract is funded by: None
Synn et al. (Fri,) studied this question.