Background/Purpose:  KL-6 is a glycoprotein expressed on and released from type 2 alveolar cells and the measurement of KL-6 in serum was developed by Kohno et al (Am J Respir Crit Care Med 1993). Serum levels of KL-6 have been reported to be higher in ILD (Ohnishi H, Am J Respir Crit Care Med 2002) and be a predictor of prognosis of ILD (Yokiyama A, Am J Respir Crit Care Med 1998). We also reported that serum levels of KL-6 increased when ILD exacerbated after administration of TNF-inhibitors in RA (Nakashita T, BMJ open 2014). Normal range of serum KL-6 is less than 500 U/ml and serum level of more than 1,000 U/ml is a predictor of poor prognosis. However, we have noticed that in some patients serum KL-6 levels are sustained in high levels even when the activity of ILD deceased. We tried to detect the factors that contribute in sustaining serum KL-6 levels high.

Methods:  Subjects were 98 patients including 52 RA, 19 diffuse SSc, and 27 limited SSc. These patients fulfilled the following requirements; 1. presence of ILD proved by chest CT, 2. no changes in chest CT findings for more than 2 years, 3. less than 5 % changes in % VC for more than 2 years, suggesting that the ILD is stable during the period. Serum KL-6 levels were checked periodically, every 2 – 6 months, from the first visit to our department. Nine variables were checked including diagnosis (RA, d-SSc, l-SSC), age, gender, ILD pattern (UIP, NSIP, organizing pneumonia), ILD grade (1 – 3 according to Nakashita), % VC, peak serum KL-6 value, peripheral blood eosinophil count, ANA titer, and RF titer. These variables were statistically analyzed.

Results: Serum KL-6 value was highest in d-SSc followed by l-SSc and RA; the mean values were 776 U/ml, 439 U/ml, and 371 U/ml, respectively (p < 0.0001). % VC values were lowest in d-SSc followed by l-SSc and RA; the mean values were 90.1 %, 98.9 %, and 107.2 %, respectively (p < 0.02). Multivariate analysis was done using 10 variables to extract factors that contribute to discriminate 2 groups, i.e. a very high KL-6 group (KL-6 >= 900 U/ml) and another group (KL6 < 900 U/ml). In a very high KL-6 group included 10 patients. Factors that contribute to discriminate 2 groups (p < 0.1) were diagnosis (RA, d-SSc or l-SSc), % VC, and peak serum KL-6 values. Multiple regression analysis was also done. Multiple regression coefficient was moderately high (0.78), but significant regression factors were diagnosis and peak KL-6 value.

Conclusion: Patients with d-SSc, low % VC and high peak KL-6 value tend to show high serum KL-6 values even when ILD is not active. Our results can contribute to avoid aggressive treatment for patients with stable but very high serum KL-6 levels.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-level-of-kl-6-a-biomarker-of-interstitial-lung-disease-ild-is-higher-in-diffuse-ssc-than-in-limited-ssc-and-ra-even-when-the-activity-of-ild-is-low/