Background/Purpose:  ILD is a frequent and potentially severe complication of CTDs. The course of ILD can be difficult to predict in this setting. The term IPAF (Interstitial Pneumonia with Auto-immune Features) has been recently created to design patients not fulfilling the diagnostic criteria for defined CTD. KL-6 (Krebs von den Lungen-6) biomarker, also known as Mucin1, is a glycoprotein produced by type II pneumocytes. Levels of serum KL-6 are well recognized to be correlated to the clinical outcome of idiopathic ILDs. However, its prognostic relevance in CTDs and IPAF-ILDs needs to be better determined.

Methods:  The levels of KL-6 of the sera of 129 patients (66 males; age 61 ± 13 years; smokers or ex-smokers: n = 56(43%) have been retrospectively analyzed using the FUJIREBIO Lumipulse Chemiluminescent enzyme immunoassay at the time of ILD diagnosis. Cut-off for normal values has been set to 500 U/mL according to previous published studies. Among the 128 patients, 61 had CTDs-ILD, 21 had IPAF-ILD, 34 had idiopathic pulmonary fibrosis (IPF), and 13 had nonspecific interstitial pneumonia (NSIP). KL-6 levels were correlated with baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) using the Spearman non parametric correlation test. Correlation of KL-6 levels with the clinical outcome (improvement/stabilization of ILD or worsening, as defined by a decrease of 10% in FVC or 15% in DLCO/death) at one year were studied using a U Mann-Whitney test.

Results:  The mean levels of KL-6 for CTDs, IPAF, IPF, and NSIP were 2204 ± 2285, 2393 ± 2172, 1802 ± 1584, and 1839 ± 1328 U/mL, respectively. KL-6 levels were over the normal value in 87 % (53/61), 90 % (19/21), 91 % (31/34) and 100 % (13/13) in CTDs, IPAF, IPF, and NSIP, respectively. Overall, KL-6 levels were negatively correlated with FVC (r=-0.2, p=0.035) and DLCO (r=-0.28, p=0.004). As regards the clinical outcome of ILD, higher levels of KL-6 were observed in patients with poor outcome (progression/death) when compared to those with better outcome (stabilization or improvement) in CTDs (2855 ± 2490 vs 1932 ± 2166 U/mL, p=0.05). Similar trends were observed in IPF (2351 ± 1908 vs 1107 ± 561, p=0.04) and in NSIP (2628 ± 1667 vs 1360 ± 543.7, p=0.18), while no difference was observed in IPAF (2418 ± 1583 vs 2388 ± 2679, p=0.33).

Conclusion:  High levels of KL-6 measured at early time points in the clinical history of CTDs-associated may be predictive of poorer outcomes. Similar trends were observed in IPF and NSIP. Further prospective studies are required to confirm these results.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-kl-6-levels-in-interstitial-lung-diseases-ilds-associated-to-connective-tissue-diseases-ctds/