Surfactant Protein D and KL-6 as Serum Biomarkers of Interstitial Lung Disease in Patients with Scleroderma

Objective. To assess whether serum concentrations of surfactant protein D (SP-D) and Krebs von den Lungen-6 (KL-6), glycoproteins expressed by type II pneumocytes, correlate with the presence of alveolitis and measures of lung function in patients enrolled in the Scleroderma Lung Study (SLS). Methods. Serum obtained at baseline screening of patients with systemic sclerosis (SSc, scleroderma) in the SLS was assayed. Alveolitis was defined by either bronchoalveolar lavage or thoracic high-resolution computed tomography (HRCT) by SLS criteria. SP-D and KL-6 levels were measured by ELISA in 66 SSc patients (44 with alveolitis, 22 without alveolitis) and in 10 healthy controls. These were compared to clinical measures of lung disease and alveolitis in the SLS patients. Results. SP-D levels were 300 214 ng/ml (mean +/- SD) in the SSc patients compared to 40 +/- 51ng/ml in controls (p < 0.0001). KL-6 levels were 1225 984 U/ml in the SSc patients and 333 +/- 294 U/ml in controls (p < 0.0001). SSc patients with alveolitis had higher levels of both SP-D and KL-6 than those without alveolitis. The level of SP-D was 353 +/- 219 ng/ml in patients with alveolitis and 161 +/- 143 ng/ml without alveolitis (p = 0.0002). The level of KL-6 was 1458 +/- 1070 U/ml in patients with alveolitis and 640 +/- 487 U/ml without alveolitis (p = 0.0001). Receiver operator characteristic curve analysis demonstrated high sensitivity and specificity of both SP-D and KL-6 for the determination of alveolitis. KL-6 and SP-D were positively correlated with maximum fibrosis scores, but not. with maximum ground-glass opacities, on HRCT. Conclusion. Serum levels of SP-D and KL-6 appear to be indicative of alveolitis in SSc patients as defined by the SLS, and are significantly higher than in SSc patients without alveolitis. Serum SP-D and KL-6 may serve as noninvasive serological means of assessing interstitial lung disease in patients with SSc. (First Release March 15 2009; J Rheumatol 2009;36:773-80; doi: 10.3899/jrheum.080633)