Diagnostic value of KL-6 in idiopathic interstitial pneumonia

Zheng, Peiyan; Liu, Xiaoqing; Huang, Huimin; Guo, Zi-Kuan; Wu, Ge; Hu, Haisheng; Cai, Chuanxu; Luo, Wenting; Wei, Nili; Han, Qin; Sun, Baoqing

doi:10.21037/jtd.2018.07.54

Cited by 25 publications

(18 citation statements)

References 25 publications

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“…Among the changed extracellular factors identified in our study, TNC and KL-6 were found to be the most significant (q < 0.05, Ratio > 4), and both tightly associated with the cytokine-mediated signaling network. Furthermore, TNC has been thought of a clinically relevant, endogenous diver of innate immunity [11,39], and plays important roles in T-lymphocyte trafficking [40], while serum KL-6 is a valuable and significant diagnostic marker of ILD and a useful predictor of clinical prognosis [12,13,41,42]. Thus, we recruited 39 COVID-19 patients and healthy controls to investigate the serum levels of TNC and KL-6.…”

Section: Discussionmentioning

confidence: 99%

Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID‐19 patients

et al. 2020

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Up to 10–20% of patients with coronavirus disease 2019 (COVID‐19) develop a severe pulmonary disease due to immune dysfunction and cytokine dysregulation. However, the extracellular proteomic characteristics in respiratory tract of these critical COVID‐19 patients still remain to be investigated. In the present study, we performed a quantitative proteomic analysis of the bronchoalveolar lavage fluid (BALF) from patients with critical COVID‐19 and from non‐COVID‐19 controls. Our study identified 358 differentially expressed BALF proteins (P < 0.05), among which 41 were significantly changed after using the Benjamini–Hochberg correction (q < 0.05). The up‐regulated signaling was found to be mainly involved in inflammatory signaling and response to oxidative stress. A series of increased extracellular factors including Tenascin‐C (TNC), Mucin‐1 (KL‐6 or MUC1), Lipocalin‐2 (LCN2), periostin (POSTN), Chitinase 3‐like 1 (CHI3L1 or YKL40), and S100A12, and the antigens including lymphocyte antigen 6D/E48 antigen (LY6D), CD9 antigen, CD177 antigen, and prostate stem cell antigen (PSCA) were identified, among which the proinflammatory factors TNC and KL‐6 were further validated in serum of another thirty‐nine COVID‐19 patients and healthy controls, showing high potentials of being biomarkers or therapeutic candidates for COVID‐19. This BALF proteome associated with COVID‐19 would also be a valuable resource for researches on anti‐inflammatory medication and understanding the molecular mechanisms of host response. Database Proteomic raw data are available in ProteomeXchange (http://proteomecentral.proteomexchange.org) under the accession number PXD022085, and in iProX (http://www.iprox.org) under the accession number IPX0002429000.

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Section: Discussionmentioning

confidence: 99%

Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID‐19 patients

et al. 2020

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“…Alessandro et al have also recently reported the persistence of high KL-6 levels in a smaller cohort of patients with fibrotic sequelae of COVID-19 longitudinally followed to 9 months [ 24 ]. Several other groups have described that dynamic change in serum KL-6 levels appears to reflect disease patterns and may be a marker of therapeutic efficacy or disease progression in other fibrotic interstitial lung diseases [ 7 , 25 , 26 ], thus implicating KL-6 as a potential biomarker for longer term sequelae of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks

et al. 2021

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Introduction Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up. Methods Prospective single centre observational study. Results Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml). Conclusions The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.

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“…In addition, we referred to the research results of Doishita et al [ 31 ] and Zheng et al [ 32 ] as well as our previous research results. [ 21 ] There was a significant difference in KL-6 levels at baseline and 52 weeks ( r = 0.325, P < .05), whereas SP-A levels did not differ significantly between these 2 time points ( r = 0.203, P > .05).…”

Section: Resultsmentioning

confidence: 99%

Krebs von den Lungen-6 and surfactant protein-A in interstitial pneumonia with autoimmune features

et al. 2021

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Interstitial pneumonia with autoimmune features (IPAF) is a special subtype of interstitial lung disease that has received worldwide attention. Krebs von den Lungen-6 (KL-6) and surfactant protein-A (SP-A) can be used as an important biomarker of interstitial lung disease, but its exact relationship with IPAF is poorly understood. A total of 65 IPAF patients were included in the study and were followed up for 52 weeks. The KL-6 and SP-A were evaluated by chemiluminescence enzyme immunoassay. The above indicators were tested at 2 time points, baseline (the first admission of patients) and 52 weeks. We also collected the indicators of antinuclear antibodies and rheumatoid factor. Based on high-resolution computed tomography evaluations, patients were divided into: aggravation, stable, and improvement group. At same time, 30 age-matched normal people as normal control were recruited, the same information was collected. Correlations among the groups were compared and analyzed. The KL-6 and SP-A level in IPAF patients were significantly higher than normal controls (fold increase = 11.35 and 1.39, both P < .001) and differed significantly at baseline and 52 weeks in IPAF (difference ratio = 37.7% and 21.3%, P < .05, both). There were significant differences at baseline and 52 weeks ( r values of aggravation, improvement, and stable groups for KL-6 were 0.705, 0.770, and 0.344, P = .001, .001, and .163, and for SP-A the r value were 0.672, 0.375, and 0.316, P = .001, .126, and .152). In aggravation group, KL-6 and SP-A were correlated with CT scores (both P < .05). Diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC), % predicted showed a progressive downward trend, with a significant difference at baseline and 52 weeks in IPAF patients (difference ratio = 23.8% and 20.6%, both P < .05). There was a significant correlation between KL-6 and FVC % predicted and DLCO (both P < .05), SP-A showed negatively correlated with DLCO, but not significantly correlated with FVC % predicted ( P < .05 and .47). This study demonstrated that KL-6 and SP-A can reflect disease progression, and both 2 play a key role at reflection of lung epithelial cell injury and fibrosis degree in IPAF.

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Diagnostic value of KL-6 in idiopathic interstitial pneumonia

Abstract: The serum KL-6 level is a valuable and significant diagnostic marker of IIP and a useful predictor of clinical prognosis.

Cited by 25 publications

References 25 publications

Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID‐19 patients

Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID‐19 patients

Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks

Krebs von den Lungen-6 and surfactant protein-A in interstitial pneumonia with autoimmune features

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