Serum KL-6 level as a biomarker of interstitial lung disease in childhood connective tissue diseases: a pilot study


Krebs von den Lungen-6 (KL-6) has been described as a promising biomarker in the diagnosis and determining the severity of interstitial lung disease in adults with connective tissue disease. This study was performed to determine whether the serum KL-6 level is useful as a biomarker for detecting the interstitial lung disease (ILD) in pediatric cases of connective tissue disease (CTD). In total, 88 patients [36 patients with systemic juvenile idiopathic arthritis (sJIA), 27 patients with juvenile systemic lupus erythematosus (JSLE), 14 patients with juvenile dermatomyositis (JDM), and 11 patients with juvenile systemic sclerosis (JSSc)] and 68 healthy controls were included in this study. Age, sex, and duration of CTD and ILD (if any) were recorded. Blood samples from all the patients and controls were examined by ELISA. Eleven of the 88 patients with CTD (12.5%) had ILD and all of them were symptomatic. Subgroup analysis indicated that eight patients had JSSc, two had JSLE, and one had systemic JIA. The median serum KL-6 level was 1450.5 U/mL (interquartile range (IQR) 742.9–2603.2) in the CTD with ILD group, 415.9 U/mL (IQR 233.4–748.4) in the CTD without ILD group, and 465.9 U/mL (IQR 273.6–1036) in the control group. KL-6 levels were significantly higher in the CTD with ILD group than the CTD without ILD group and the control group (p = 0.003). At a cut-off of 712.5 U/ml identified by ROC curve, serum KL-6 yielded a sensitivity of 81% and specificity of 72% for CTD with ILD group. There was no significant difference in serum KL-6 level among the disease subgroups (sJIA, JSLE, JSSc, JDM), in either the CTD with ILD group or the CTD without ILD group (p > 0.05). In conclusion, KL-6 is a useful biomarker of CTD with ILD in pediatric patients.

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All co-authors contributed substantial contributions to the conception and design of the work; the acquisition, analysis, and interpretation of data for the work. All co-authors made drafting for the work and revising it critically for important intellectual content and made final approval of the version to be published. All co-authors contributed to agreement to be accountable for all aspects of the work in ensuring that the questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All co-authors are familiar and take full responsibility for all aspects of the study and the final manuscript. AAK, HC, AA, and OK contributed to the conception and design of the study, data analysis, and manuscript writing. AAK, AA, AA, and MY had substantially contributed to conception and design of the study and to data analysis. AA, MY, and MK contributed to data collection and data input. HC, KB, OK, and AA contributed to data analysis and manuscript writing. SS, AA, and KB contributed to data analysis and critical revisions. AAK, HC, and OK made final contributions to the conception and design, revision of draft manuscript, and approval of the manuscript to be submitted for publication. All the authors read and approved the final version of the manuscript.

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Correspondence to Ozgur Kasapcopur.

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Kilinc, A.A., Arslan, A., Yildiz, M. et al. Serum KL-6 level as a biomarker of interstitial lung disease in childhood connective tissue diseases: a pilot study. Rheumatol Int 40, 1701–1706 (2020).

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  • Interstitial lung diseases
  • Connective tissue diseases
  • Systemic sclerosis
  • Juvenile idiopathic arthritis
  • Systemic lupus erythematosus
  • KL-6