Abstract Background Hermansky-Pudlak Syndrome (HPS) type I is a rare autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and progressive pulmonary fibrosis—the latter being a leading cause of morbidity and mortality. While lung transplantation remains the only definitive treatment in advanced stages, there is an unmet need for reliable, non-invasive biomarkers to monitor disease progression. Carbohydrate antigen 15-3 (CA 15-3), a tumor-associated glycoprotein traditionally used in breast cancer surveillance, has recently been implicated in fibrotic and inflammatory lung diseases. This study investigates the potential of CA 15-3 as a biomarker for pulmonary fibrosis severity in patients with HPS. Methods A cross-sectional observational study was conducted involving 25 patients aged 20-50 years with genetically confirmed HPS and radiologically established pulmonary fibrosis. Diagnosis was based on high-resolution computed tomography (HRCT) findings and a restrictive pattern on pulmonary function testing (PFT). Exclusion criteria included malignancy, rheumatologic disease, recent respiratory infection, or immunosuppressive therapy. Serum CA 15-3 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Correlations between CA 15-3 levels and Forced Vital Capacity (FVC) were analyzed to assess associations with disease severity. Results Elevated serum CA 15-3 levels were observed in patients with moderate-to-severe restrictive patterns on PFTs. CA 15-3 potentially distinguishes fibrotic vs non fibrotic patterns. A statistically significant inverse correlation was identified between CA 15-3 levels and FVC (r = -0.51; 95% CI: -0.75 to -0.14), indicating that higher CA 15-3 concentrations were associated with greater impairment of pulmonary function. Conclusions This study demonstrates a significant inverse relationship between CA 15-3 levels and pulmonary function in patients with HPS-related fibrosis. These findings suggest that CA 15-3 may serve as a promising non-invasive biomarker for disease severity and progression in HPS, potentially detecting fibrotic activity before overt declines in PFTs. If validated in larger, longitudinal cohorts, CA 15-3 could transform the clinical approach to monitoring progressive pulmonary fibrosis in HPS. By providing an earlier and more sensitive indicator of disease activity than traditional PFTs, CA 15-3 may enable proactive, personalized interventions—optimizing management, delaying the need for lung transplantation, and ultimately improving quality of life for this vulnerable patient population. This abstract is funded by: None
Caro et al. (Fri,) studied this question.