Background/Purpose: Interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (SSc). KL-6, a mucin-like glycoprotein highly expressed on type II pneumocytes, is known as a circulating biomarker for lung injury and various forms of ILD. Previous cross-sectional studies have shown that circulating KL-6 level is elevated in patients with SSc-ILD and is inversely correlated with percent predicted forced vital capacity (%FVC). We have recently found that elevated KL-6 level at baseline is an independent predictor of %FVC decline and mortality, although information on serial changes of KL-6 during the course of SSc is scarce. In this study, we investigated clinical utility of serial KL-6 measurement in patients with SSc-ILD using a prospective cohort.

Methods: We enrolled 58 consecutive patients who were diagnosed as having SSc between 2006 and 2012. These patients were selected from our SSc database, based on fulfillment of 1980 American College of Rheumatology preliminary criteria, disease duration ≤8 years at diagnosis, follow-up period >2 years, availability of pulmonary function test (PFT) and chest high-resolution CT (HRCT) at diagnosis, and availability of serial PFT results in an interval of <2 years. Serum KL-6 was measured using a monoclonal antibody-based kit (Eidia, Japan) at every visit. Clinically meaningful change of KL-6 levels was defined as 20% increase or decrease from the baseline. All clinical information had been prospectively recorded on the database.  

Results: Twenty-three patients (40%) were classified as having diffuse cutaneous SSc, and 39 (67%) had ILD detected by HRCT at diagnosis. Baseline serum KL-6 level was significantly elevated in SSc patients with ILD than in those without (P = 0.001), and was higher in extensive than in limited disease in patients with ILD (P < 0.001). In 19 patients without ILD at diagnosis, KL-6 was below 500 U/ml at baseline, and was pretty stable during disease course. In contrast, baseline KL-6 level was highly variable in patients with ILD: 51% <500 U/ml, 18% 500-1000 U/ml, and 31% >1000 U/ml. KL-6 levels changed with variation in patients with ILD: 7 increase, 19 unchanged, and 13 decrease during 4.5 ± 1.1 years (range 2.0 – 6.3 years), regardless of the treatment. Yearly change of %FVC was inversely correlated with both the final KL-6 level and the final to initial KL-6 ratio (p = 0.047 and <0.001, respectively). Moreover, 20 patients who showed sustained increase of KL-6 (>500 U/ml) experienced significantly higher %FVC deterioration than those who did not (p = 0.03). Eleven patients with ILD received treatment with oral or intravenous cyclophosphamide during disease course. In these patients, KL-6 level significantly reduced at 12 months after initiation of the treatment (p = 0.045).

Conclusion: Serial measurement of KL-6 may be useful in predicting progression of pulmonary function and in evaluating treatment response of cyclophosphamide in patients with SSc-ILD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-utility-of-serial-kl-6-measurement-in-interstitial-lung-disease-associated-with-systemic-sclerosis/