Serum KL-6 and Surfactant Proteins Show Diagnostic Utility in Fibrotic ILD
According to a systematic review and meta-analysis evaluating the diagnostic performance of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D), blood-based biomarkers may help identify fibrotic interstitial lung diseases (ILDs), offering a less invasive adjunct to imaging and pulmonary function testing.
High-resolution CT and pulmonary function tests remain the diagnostic standard but are limited by radiation exposure, access, and interobserver variability. To assess whether serum or bronchoalveolar lavage biomarkers could aid diagnosis, investigators analyzed 19 studies including 3320 participants. Diagnostic accuracy was measured against histopathology or HRCT using pooled sensitivity and specificity estimates.
KL-6 demonstrated a pooled sensitivity of 0.74 and specificity of 0.90 across 16 studies, indicating strong rule-in potential for fibrotic ILD. SP-A showed similar specificity (0.91) but slightly lower sensitivity (0.71), while SP-D demonstrated moderate sensitivity (0.73) and specificity (0.78).
The authors concluded that “KL-6 and SP-A demonstrated high specificity and moderate sensitivity, supporting their use to rule in fibrotic ILDs.” However, diagnostic performance varied by disease subtype. Subgroup analyses revealed significantly lower specificity in autoimmune-associated ILDs compared with idiopathic interstitial pneumonia. For example, KL-6 specificity was 0.87 in autoimmune ILD versus 0.98 in idiopathic disease.
These findings suggest that biomarker thresholds may require adjustment in connective tissue disease–associated ILD and that single-marker testing may not be sufficient in all contexts. The authors noted that reduced diagnostic accuracy in autoimmune ILDs indicates that “tailored thresholds or combined testing may be necessary.”
Reference
Tzang CC, Lin WC, Huang ES, et al. Interstitial lung disease biomarkers: a systematic review and meta-analysis. Clin Chim Acta. 2025;577:120473. doi:10.1016/j.cca.2025.120473
