The role of serum KL-6 measurement in common pediatric respiratory infections

doi:10.1007/s10156-005-0416-9

Journal of Infection and Chemotherapy

Volume 12, Issue 1, 2006, Pages 22-24

https://doi.org/10.1007/s10156-005-0416-9 Get rights and content

Abstract

KL-6 is a useful marker for interstitial pneumonia of various origins. However, the role of KL-6 in common pediatric respiratory infections is largely unknown. In order to determine whether the KL-6 level is elevated during respiratory infection, and whether KL-6 is a useful biomarker for the disease activity, we evaluated serum KL-6 levels in 132 children with various respiratory infections. KL-6 levels were significantly higher in patients with measles, influenza, or respiratory syncytial virus infection than in the control subjects. On the other hand, KL-6 levels in patients with bacterial infections such as mycoplasma, chlamydia, or pertussis were comparable to the control values. In patients with viral infections, high KL-6 levels, as defined by the mean plus 2 standard deviations of the control group, significantly correlated with low SpO₂ or days of O₂ administration, but did not correlate with C-reactive protein or white blood cell counts. These results indicate that measurement of serum KL-6 levels is helpful for the management of common pediatric respiratory infections.

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Citation Excerpt :
Over the past few decades, research efforts for biomarkers of RA-ILD have focused on Krebs von den Lungen-6 (KL-6) [3], the surfactant protein A and surfactant protein D (SP-D) [4], antibodies against cyclic citrullinated peptide (CCP) [5,6] and peptidylarginine deiminase type 3/4 [7], and the matrix metalloproteinases [8]. Among them, KL-6 and SP-D have been confirmed and gradually applied in clinics, but abnormal expressions of KL-6 and SP-D may also occur in respiratory diseases involving destruction or regeneration of alveolar epithelial cells, such as lung cancer [9], respiratory infections [10,11], and drug-induced pneumonia [12]. Thus, it is imperative to further explore the pathogenesis of ILD and search for reliable biomarkers.
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In this study, we detected CXCL16 levels in patients with rheumatoid arthritis-associated ILD (RA-ILD) and examined the critical role of the CXCL16/CXCR6 axis in the proliferation and collagen production of human pulmonary fibroblasts (MRC-5 cells). The effect of anti-CXCL16 antibody on the bleomycin-induced fibrogenesis in cultured MRC-5 cells was also evaluated.
Our results indicated that serum soluble CXCL16 was significantly higher in RA-ILD patients and also associated with the severity of lung fibrosis. CXCL16 facilitates fibrosis by enhancing proliferation, migration, and collagen production of MRC-5 cells. Furthermore, a synergistic fibrogenic effect of CXCL16 and bleomycin has been found. CXCL16 stimulated the activation of PI3K/AKT/FOXO3a signaling pathway in MRC-5 cells, and the inhibition by specific inhibitors Wortmannin and LY294002, or knockdown of CXCR6 by siRNA also suppressed the biological functions of MRC-5 cells mediated by CXCL16. Similarly, down-regulation of CXCR6 also partly blocked BLM-induced fibrogenesis in MRC-5 cells.
CXCL16/CXCR6 axis promotes proliferation and collagen production of MRC-5 cells by the PI3K/AKT/FOXO3a signaling pathway, and inhibition of the CXCL16/CXCR6 axis may provide a new therapeutic strategy targeting pulmonary fibrosis.
Serum KL-6 differentiates neuroendocrine cell hyperplasia of infancy from the inborn errors of surfactant metabolism
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The study was conducted in order to determine if the glycoprotein KL-6 is a useful biomarker in differentiating neuroendocrine cell hyperplasia of infancy (NEHI), a benign form of children's interstitial lung disease, from the more severe inborn errors of surfactant metabolism (IESM), since their clinical presentation can be similar.
Serum KL-6 levels were measured in 10 healthy control children, 6 with NEHI and 13 with IESM (4 with surfactant protein C (SP-C) and 9 with ABCA3 mutations). The initial clinical presentation, findings on previous CT scans and interstitial lung disease (ILD) scores at the time of KL-6 testing were compared. Correlations of KL-6 levels with age and with interval from lung biopsy were evaluated.
The median (range) KL-6 levels were 265 (1–409), 194 (47–352), 1149 (593–4407) and 3068 (726–9912) U/ml for the control, NEHI, SP-C and ABCA3 groups, respectively. When compared with the control and NEHI groups, median KL-6 levels were significantly higher in the SP-C (p<0.01; p = 0.01, respectively) and ABCA3 groups (p<0.001; p = 0.001, respectively); however, there was no difference between the control and NEHI groups (p = 0.91). An inverse relationship was seen between KL-6 levels and age in the IESM groups, but not in the NEHI or control groups. Children with NEHI had similar presenting clinical features and were equally symptomatic at the time of KL-6 measurement as those with IESM.
Children with NEHI have normal KL-6 levels, in contrast to those with IESM, who have elevated serum KL-6 levels; serum KL-6 may be a useful biomarker in distinguishing between these entities when their clinical presentations overlap.
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The role of serum KL-6 measurement in common pediatric respiratory infections

Abstract

Chest

J Pediatr

J Pediatr

Tuberc Lung Dis

Toxicol Appl Pharmacol

Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma

Jpn J Clin Oncol