Serum KL-6 Levels Research Articles

Mycophenolate mofetil after tacrolimus for refractory clinically amyopathic dermatomyositis: a case report

Dermatomyositis (DM) positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, mainly when linked with rapidly progressive interstitial lung disease (RP-ILD), is considered a refractory disease. Our report describes a critical case of clinically amyopathic dermatomyositis (CADM) with RP-ILD that tested positive for both anti-MDA5 and anti-Ro-52 antibodies. The patient showed a limited response to a combined therapy regimen of prednisone, iguratimod, and tacrolimus. However, after adjunct therapy with mycophenolate mofetil (MMF), the patient’s condition was controlled, his serum KL-6 levels decreased, and anti-MDA5 antibodies became negative. During the 68-week follow-up, the patient’s condition remained stable, with a satisfactory quality of life. This report also discusses the potential role of inflammatory cytokines in the pathophysiology of CADM and RP-ILD. Further research is required to confirm these results and investigate the application of MMF in maintenance therapy for CADM-associated RP-ILD.

Correlation between CT-based phenotypes and serum biomarker in interstitial lung diseases

BackgroundThe quantitative analysis of computed tomography (CT) and Krebs von den Lungen-6 (KL-6) serum level has gained importance in the diagnosis, monitoring, and prognostication of interstitial lung disease (ILD). However, the associations between quantitative analysis of CT and serum KL-6 level remain poorly understood.MethodsIn this retrospective observational study conducted at tertiary hospital between June 2020 and March 2022, quantitative analysis of CT was performed using the deep learning-based method including reticulation, ground glass opacity (GGO), honeycombing, and consolidation. We investigated the associations between CT-based phenotypes and serum KL-6 measured within three months of the CT scan. Furthermore, we evaluated the performance of the combined CT-based phenotypes and KL-6 levels in predicting hospitalizations due to respiratory reasons of ILD patients.ResultsA total of 131 ILD patients (104 males) with a median age of 67 years were included in this study. Reticulation, GGO, honeycombing, and consolidation extents showed a positive correlation with KL-6 levels. [Reticulation, correlation coefficient (r) = 0.567, p < 0.001; GGO, r = 0.355, p < 0.001; honeycombing, r = 0.174, p = 0.046; and consolidation, r = 0.446, p < 0.001]. Additionally, the area under the ROC of the combined reticulation and KL-6 for hospitalizations due to respiratory reasons was 0.810 (p < 0.001).ConclusionsQuantitative analysis of CT features and serum KL-6 levels ascertained a positive correlation between the two. In addition, the combination of reticulation and KL-6 shows potential for predicting hospitalizations of ILD patients due to respiratory causes. The combination of reticulation, focusing on phenotypic change in lung parenchyma, and KL-6, as an indicator of lung injury extent, could be helpful for monitoring and predicting the prognosis of various types of ILD.

Combined use of serum ferritin and KL-6 levels as biomarkers for predicting COVID-19 severity

ObjectivesTo assess the value of serum ferritin and Krebs von den Lungen-6 (KL-6) levels for predicting severe COVID-19 (death or requirement for invasive mechanical ventilation [IMV]/high-flow oxygen). MethodsData were analyzed on 2495 patients with COVID-19 from February 2020 to November 2022 using data from a nationwide COVID-19 database. ResultsPatients with high KL-6 and low ferritin levels were older with more comorbidities and higher mortality rates, whereas those with high ferritin and low KL-6 levels were younger, predominantly male, and more likely to need IMV. A high level of both markers was strongly associated with critical outcomes (adjusted odds ratio: 13.6, 95% confidence interval: 8.58–21.5). The combination of both markers had higher predictive value than either marker alone (area under the curve: 0.709, 0.745, and 0.781 for KL-6, ferritin, and KL-6 + ferritin, respectively). ConclusionsThe combination of both markers accurately predicted COVID-19 severity.

Correlation of serum Krebs von den Lungen-6 levels with fibrosis score on high resolution chest tomography and pulmonary function parameters in treatment naïve Idiopathic Pulmonary Fibrosis.

While serum Krebs von den Lungen-6 (KL-6) has been found to be a helpful biomarker in interstitial lung diseases for evaluating disease severity and progression, especially in connective tissue disease-associated interstitial lung disease (CTD ILD) and idiopathic non-specific interstitial pneumonia (NSIP), data on correlation of serum KL-6 levels with radiological fibrosis and pulmonary function parameters is lacking in treatment naïve Idiopathic Pulmonary Fibrosis (IPF) patients. Serum KL-6 levels were measured in thirty-nine treatment naïve newly detected IPF patients using automated immunofluorescence enzyme assay (AIA) by Tosoh Corporation, bioscience division, Tokyo, Japan. Fibrosis score was calculated by independent visual assessment of the pattern and severity of abnormalities on high resolution computed tomography (HRCT) thorax. HRCT fibrosis scores were correlated with serum KL-6 levels and pulmonary function parameters like forced vital capacity (FVC), diffusion capacity of lung for carbon monoxide (DLco). Median value of serum KL-6 levels was 1519 U/ml (range 199.41-6055 U/ml). There was positive correlation of serum KL-6 with HRCT fibrosis score (r=0.692, p<0.001) and negative correlation with FVC (r=-0.511, p=0.001) and DLco (r=-0.354, p=0.043). In the HRCT fibrosis score pattern subset analysis, the presence of reticulation revealed weak negative and statistically insignificant correlation (r=-0.116, p=0.481) while traction bronchiectasis and honeycombing exhibited statistically significant positive correlation (r=0.425, p=0.007; r=0.584, p<0.001 respectively) with serum KL-6 levels. Serum KL-6 levels showed a positive correlation with the degree of fibrotic abnormalities on HRCT thorax and pulmonary function parameters, indicating a potential use of serum KL-6 in monitoring of parenchymal fibrosis in Idiopathic Pulmonary fibrosis.

Prognostic performance of Krebs von den Lungen-6, surfactant protein A, surfactant protein D levels in the serum and bronchoalveolar lavage fluid in chronic fibrosing interstitial pneumonia: a retrospective study

BackgroundThe serum markers Krebs von den Lungen-6 (KL-6), surfactant protein A (SP-A), and surfactant protein D (SP-D) have been used for the diagnosis, differential diagnosis, and prognosis prediction of interstitial pneumonia. However, the significance of measuring the serum and bronchoalveolar lavage fluid (BALF) KL-6, SP-D, and SP-A levels in predicting the prognosis of chronic fibrosing interstitial pneumonia (CFIP), idiopathic pulmonary fibrosis, and idiopathic nonspecific interstitial pneumonia remains unclear. We aimed to clarify the significance of measuring the serum and BALF KL-6, SP-A, and SP-D levels in predicting the prognosis of patients with CFIP.MethodsAmong 173 patients who were diagnosed with CFIP between September 2008 and February 2021, 39 who underwent bronchoalveolar lavage were included in this study. Among these, patients experiencing an annual decrease in forced vital capacity (FVC) of ≥10% or those facing challenges in undergoing follow-up pulmonary function tests owing to significant deterioration in pulmonary function were categorized as the rapidly progress group. Conversely, individuals with an annual decrease in the FVC of <10% were classified into the slowly progress group. The serum and BALF KL-6, SP-D, and SP-A levels, as well as BALF/serum SP-D and SP-A ratios were compared between the two groups.ResultsAmong the patients with CFIP, the BALF SP-D level (p=0.0111), BALF SP-A level (p<0.0010), BALF/serum SP-D ratio (p=0.0051), and BALF/serum SP-A ratio (p<0.0010) were significantly lower in the rapidly than in the slowly progress group (p<0.0010). The receiver operating characteristics analysis results demonstrated excellent performance for diagnosing patients with CFIP, with the BALF SP-D level (area under the curve [AUC], 0.7424), BALF SP-A level (AUC, 0.8842), BALF/serum SP-D ratio (AUC, 0.7673), and BALF/serum SP-A ratio (AUC, 0.8556). Moreover, the BALF SP-A level showed a notably superior CFIP diagnostic capability. Survival analysis using the Kaplan–Meier method revealed that patients with a BALF SP-A level of <1500 ng/mL and BALF/serum SP-A ratio of <15.0 had poor prognoses.ConclusionsOur results suggest that BALF SP-A measurement may be useful for predicting the prognosis in patients with CFIP.

Exploratory analysis of serum Krebs von den Lungen-6, blood gas analysis & Brixia score in determining COVID-19 severity & mortality.

Background & objectives Krebs von den Lungen-6 (KL-6) is primarily expressed by the damaged type II pneumocytes. In this context, the relationship of KL-6 with blood gas analysis (BGA) parameters and Brixia score is still limitedly discussed. This study aims to analyze the correlation of KL-6, BGA and Brixia scores to the severity and mortality of COVID-19. Methods A cross-sectional study was conducted in adult COVID-19 positive individuals at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, from March to August 2021. KL-6, BGA, and Brixia scores were compared according to severity (severe vs. non-severe) and mortality (non-survivor vs. survivor). The receiver operating characteristic (ROC) analysis was also performed to define the optimal cut-off, sensitivity, as well as the specificity of KL-6, BGA and Brixia scores to determine the COVID-19 severity and mortality. Results Total 35 severe and 20 non-severe COVID-19 positive individuals were enrolled in this study. Of those, there were 22 non-survivors. No significant difference in serum KL-6 levels was observed in the severity and mortality groups. KL-6 and HCO3- had positive correlation in the severe group (r=0.37). KL-6 and Brixia scores showed a significant negative correlation among COVID-19 positive individuals (r=-0.283; P=0.036). KL-6 and Brixia scores together served as the best severity markers in the current study [AUC 0.809 (0.697-0.920); Sn/Sp=0.686/0.900)], followed by KL-6 and P/F ratio [AUC 0.800 (0.637-0.963); Sn/Sp=0.971/0.750]. Interpretation & conclusions The findings of this study suggest that KL-6 has the potential to be a useful adjunct laboratory parameter to the BGA and Brixia score representing COVID-19 severity and mortality.

An in-depth investigation of serum Krebs von den Lungen-6 and other biomarkers in COVID-19 severity and mortality.

Krebs von den Lungen-6 (KL-6) is a glycoprotein mainly expressed by type II pneumocytes and recently known as a lung injury biomarker. However, the number of studies is still limited, especially in Indonesian COVID-19 populations. Therefore, we aim to provide correlation, sensitivity, and specificity analyses of KL-6 and other biomarkers in Indonesian COVID-19 severity and mortality. We conducted a cross-sectional study involving adult COVID-19 patients at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, between March 26, 2021, and August 25, 2021. KL-6 and other biomarker levels were compared according to severity (severe versus non-severe) and mortality (non-survivor versus survivor). We also included the receiver operating characteristic analysis to define the optimal cut-off, sensitivity, and specificity of KL-6 to determine COVID-19 severity and mortality. We enrolled 78 COVID- 19 patients (23 non-survivors), including 39 non-severe and 39 severe patients. There was no significant difference in serum KL-6 levels, neither in severity nor mortality groups. KL-6 had the strongest positive correlations with ferritin in severe patients (r=0.313) and non-survivors (r=0.467). We observed that the best sensitivity was KL-6 combined with platelet-to- lymphocyte ratio (PLR) (0.818) in severe patients and with neutrophil-to-lymphocyte ratio (NLR)/PLR/ferritin/C-reactive protein (0.867) in non-survivors. In contrast, the best specificity was found when KL-6 was combined with NLR/D-dimer (0.750) in severe patients and with D-dimer (0.889) in non-survivors. Serum KL-6 is a useful auxiliary laboratory evaluation index for COVID-19 lung injury to depict its severity and mortality.

Serum Krebs von den Lungen-6 as a potential biomarker for distinguishing combined pulmonary fibrosis and emphysema from chronic obstructive pulmonary disease: A retrospective study

BackgroundThe presence of fibrotic interstitial lung disease (ILD) is relatively common in patients with emphysema. This has been designated combined pulmonary fibrosis and emphysema (CPFE). CPFE had worse prognosis than emphysema alone. Krebs von den Lungen-6 (KL-6) levels as a biomarker of alveolar type 2 epithelial cell injury, which is widely used to identify the presence of ILD, whether it can differentiate CPFE from COPD remains unknown. Methods259 patients from Xiangya Hospital with diagnosis of COPD, with or without ILD, and who had KL-6 tests were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. ResultsAmong 259 patients, 52 patients were diagnosed with CPFE. The mean age was 67.39 ± 8.14 yeas. CPFE patients had higher ratio of rheumatic diseases (21.2 % vs 7.2 %, P = 0.003). CPFE patients exhibited higher values of FEV1 (1.97 vs 1.57, P = 0.002) and FEV1/FVC ratio (69.46 vs 57.64, P < 0.001) compared to COPD patients. CPFE patients had higher eosinophil counts, percentage of eosinophils, lactate dehydrogenase, total bilirubin levels and lower platelet counts. Serum KL-6 levels were higher in CPFE group compared to COPD group (574.95 vs 339.30 U/mL, P < 0.001). Multiple logistic regression showed that KL-6 level was an independent predictive factor for the presence of ILD among COPD patients. The AUC of serum KL-6 levels to differentiate CPFE was 0.711, with 95 % CI being 0.635 to 0.787. The cutoff point of KL-6 level was 550.95 U/mL with 57.7 % sensitivity and 79.7 % specificity for the discrimination of CPFE from COPD. ConclusionCPFE patients show higher KL-6 levels compared to isolated COPD, suggesting the potential of KL-6 as a practical screening tool for interstitial lung disease, specifically CPFE. A KL-6 threshold of 550.95 U/mL in COPD patients may indicate a high need for high-resolution chest computed tomography to detect fibrosis.

Seasonal fluctuation of serum Krebs von den Lungen-6 levels in systemic sclerosis-associated interstitial lung disease.

To evaluate whether seasonal changes influence fluctuations in serum Krebs von den Lungen-6 (KL-6) levels in systemic sclerosis-related interstitial lung disease (SSc-ILD). Summer was defined as the period between July and September, and winter as between December and February. The study was conducted between 2015 and 2016, with a focus on these two seasons. A diagnosis of ILD and ILD progression overtime were evaluated using chest computed tomography. Among patients with SSc-ILD, those with data on serum KL-6 and lactate dehydrogenase (LDH) levels in the 2015 winter, 2015 summer, and 2016 winter seasons were included. Patients with comorbidities that could affect serum KL-6 levels were excluded. Of 60 patients with SSc-ILD, 52 (86.7%) had stable ILD, 5 (8.3%) had worsened ILD, and 3 (5.0%) had improved ILD. Serum KL-6 levels were significantly higher during the winter than those during the summer (2015 winter vs. 2015 summer: 649 U/mL vs. 585 U/mL, p < .0001; 2016 winter vs. 2015 summer: 690 U/mL vs. 585 U/mL, p < .0001). No significant differences were observed between the winters of 2015 and 2016 (649 U/mL vs. 690 U/mL, p = .78). However, serum LDH levels did not exhibit seasonal fluctuations (2015 winter vs. 2015 summer: 203 U/L vs. 199 U/L, p = .3; 2016 winter vs. 2015 summer: 201 U/L vs. 199 U/L, p = .6; 2015 winter vs. 2016 winter: 203 U/L vs. 201 U/L, p = .24). Seasonal fluctuations in serum KL-6 levels were observed in patients with SSc-ILD.

Nintedanib combined with immunosuppressive agents improves forced vital capacity in connective tissue disease-associated PF-ILD: a single-center study

BackgroundIn 2020, Nintedanib (NTB), a tyrosine kinase inhibitor, was the first drug approved worldwide for treating progressive fibrosing interstitial lung disease (PF-ILD). This study evaluated the efficacy and safety of NTB in Japanese patients with CTD-associated PF-ILD in a real-world setting, as there are few reports on this topic. We also evaluated the efficacy and safety of combination therapy with NTB and immunosuppressive agents (IS).MethodsCTD-associated PF-ILD patients receiving NTB at our institution were included in this retrospective study. To evaluate the efficacy and safety of NTB, we investigated changes in forced vital capacity (FVC) (%), diffusing capacity for carbon monoxide (DLCO) (%), monthly change in FVC (%/month), serum Krebs von den Lungen-6 (KL-6) levels (U/mL) before and after NTB treatment, and adverse events (AEs) during NTB treatment. Moreover, to evaluate the efficacy of the NTB + IS combination therapy, we divided the patients into two groups: one received only NTB (NTB group), and the other received both NTB and IS (NTB + IS group) following the diagnosis of CTD-associated PF-ILD. We analyzed the differences in the changes of these variables between the two groups.ResultsTwenty-six patients with CTD-associated PF-ILD were included. After NTB treatment, there were no significant deteriorations in FVC (%) and DLCO (%), while the monthly change in FVC (%/month) significantly increased (p < 0.001). The changes in FVC (%) and the monthly change in FVC (%/month) were significantly greater in the NTB + IS group than in the NTB group. Following NTB treatment, the mean serum KL-6 levels significantly decreased (p < 0.001). AEs associated with NTB in this study were similar to those in previous clinical trials, and there was no significant difference in the incidence of AEs between the two groups.ConclusionsThis study demonstrates that NTB is an effective medication for slowing the progression of CTD-associated PF-ILD in real-world settings. NTB + IS combination therapy for CTD-associated PF-ILD may be more effective than NTB alone in slowing the progression of CTD-associated PF-ILD.

Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.

Risk prediction modelling in idiopathic inflammatory myositis-associated interstitial lung disease based on seven factors including serum KL-6 and lung ultrasound B-lines.

To develop a user-friendly nomogram-based predictive model for interstitial lung disease (ILD) in patients with idiopathic inflammatory myositis (IIM). A retrospective study was conducted at Shantou Central Hospital, encompassing 205 IIM patients diagnosed between January 2013 and December 2022. We used the LASSO regression method in the discovery set to select features for model construction, followed by efficacy verification through AUC of ROC. Afterwards, KL-6 values and LUS B-lines number were added into this model to evaluate whether these 2 factors added to the model efficiency. Finally, a web version was constructed to make it more available. Among the 205 IIM patients, 115 (56.1%) patients were diagnosed with ILD, and 90 (43.9%) did not. The predictive model, derived from the training set, comprised four independent risk factors, including age, presence of respiratory symptoms, anti-melanoma differentiation-associated gene 5 (MDA-5) antibody positivity, and anti-aminoacyl transfer RNA synthetase (anti-ARS) antibodies positivity. Notably, anti-TIF1-γ antibody positivity emerged as a protective factor. The AUC of the ROC based on these 5 factors was 0.876 in the training set and 0.861 in the validation set. The AUC of the ROC based on the 5 factors plus KL-6 was 0.922, 5 factors plus B-line number was 0.949 and 5 factors plus both KL-6 and B-line number was 0.951. Accordingly, a nomogram and a web version were developed. This predictive model demonstrates robust capability to assess ILD risk in IIM patients, particularly when augmented with serum KL-6 level or/and LUS B-line number.

Multivariate logistic regression analysis of poor prognosis of dermatomyositis and clinical value of ferritin/Kl-6 in predicting prognosis.

Dermatomyositis (DM) is a rare inflammatory disease. Our research focuses on predicting poor prognosis in DM patients and evaluating the prognostic significance of ferritin and Salivary Sugar Chain Antigen-6 (KL-6) through multivariate logistic regression analysis. Between February 2018 and April 2020, 80 DM patients at our hospital were categorized into MDA5 positive (n=20) and negative (n=60) groups. We conducted multivariate logistic regression to determine DM's poor prognosis risk factors and evaluate ferritin/KL-6's predictive value for prognosis. Analysis showed no gender, age, body mass index (BMI), or lifestyle (smoking, drinking) differences, nor in dyspnea, muscle weakness, skin ulcers, and acetylcysteine treatment effects (p>0.05). Significant differences emerged in arrhythmias, interstitial pneumonia, C-reactive protein, albumin, and lactate dehydrogenase levels (p<0.05). Before treatment, differences were negligible (p>0.05), but post-treatment, serum KL-6 and ferritin levels dropped. MDA5 positive patients had elevated serum KL-6 and ferritin levels than survivors (p<0.05), with a strong correlation to DM. Combined diagnosis using serum KL-6 and ferritin for DM prognosis showed area under curves of 0.716 and 0.634, significantly outperforming single-index diagnoses with an area under curve (AUC) of 0.926 (p<0.05). Serum KL-6 and ferritin show marked abnormalities in DM, useful as indicators for evaluating polymyositis and DM conditions. However, the study's small sample size is a drawback. Expanding the sample size is essential to monitor serum KL-6 and ferritin changes in DM patients under treatment more closely, aiming to improve clinical assessment and facilitate detailed research.

P136 KL6 and IL-18 levels are negatively correlated with respiratory function tests and interstitial lung disease extent assessed on high-resolution computed tomography in patients with systemic sclerosis-related interstitial lung disease

Abstract Background/Aims Serum biomarkers have been suggested as indicators for pulmonary damage with clinical value in the diagnosis and prognosis of SSc-ILD. We aim to investigate the role of serum biomarkers (Krebs von den Lungen-6 KL-6, IL-18 and IL- 18BP) as potential biomarkers reflecting the severity of SSc-ILD as assessed through high-resolution computed tomography (HRCT) and pulmonary function tests (PFT). Methods A cross-sectional study including patients with SSc fulfilling the 2013 ACR/EULAR criteria was performed. Patients were classified according to disease duration and pulmonary involvement. All SSc patients underwent chest HRCT scans and pulmonary function test at baseline. Serum concentration of KL-6, IL8 and IL18BP were determined usingsandwich ELISA technique (solid phase sandwich Enzyme Linked-Immunosorbent Assay), with kits from MyBiosource for KL-6 and from Invitrogen for IL18 and IL18BP. A semiquantitative grade of ILD extent was evaluated through HRCT scan (grade 1, 0-20%; grade 2, &amp;gt;20%). Extensive lung disease was defined as &amp;gt; 20% of lung involvement on HRCT, and FVC &amp;lt;70% predicted and limited lung involvement as ≤ 20% of ILD involvement on HRCT,and an FVC ≥70% predicted. Results 74 patients were included, 27% were male, with a mean age of 57.5±15 years. 28 patients had ILD (38%). 64 % of patients had &amp;lt;20% of ILD extent classified through HRCT scan. SSc-ILD patients had elevated serum KL- 6 and IL-18 levels compared to patients without ILD (p = 0.003 and p = 0.04). A negative correlation between KL-6 levels and %FVC (β=-0.25, p 0.037) and %DLCO (β=-0.28, p 0.02) and between IL-18 levels and %FVC (β=-0.20, p 0.03) and %DLCO (β=-0.14, p 0.04) were found. Serum KL-6 and IL-18 levels successfully differentiated grades I and II (p = 0.028 and p = 0.021). Semiquantitative grades of ILD on the HRCT scan were significantly proportional to the KL-6 (p 0.01) and IL-18 (p = 0.03). A positive correlation between extensive lung disease and KL-6 (β = 0.61, p 0.007) but not with IL-18 was found. Conclusion Serum KL-6 levels and IL-18 were increased in patients with SSc-ILD and showed a positive correlation with ILD severity as measured using a semiquantitative HRCT grading scale and a negative correlation with PFT parameters. Disclosure C. Sieiro Santos: None. S. Calleja Antolín: None. J. de la Calle Lorenzo: None. E. Bollo de Miguel: None. E. Díez Álvarez: None.

Ciplukan (Physalis angulata Linn) Bioactivity against Bleomycin-Induced Pulmonary Fibrosis in Mice by reducing Subpleural Fibrosis, KL-6 Level and Anti-Inflammatory properties

Pulmonary fibrosis is a fatal lung disease with unknown pathogenesis and limited treatment options. Herbal medicine began to be developed as an antifibrosis drug for this disease. Ciplukan plant (Physalis angulata Linn.), is a wild plant that has been widely used for generations as traditional Indonesian medicine for various diseases; but has never been studied as an antifibrosis. This study aimed to determine Ciplukan herb ethanol extract (CPL) bioactivity as antifibrosis in pulmonary fibrosis disorders in experimental mice model induced by bleomycin. A total of 35 male mice and 35 female mice of the ddy strain was divided into 7 groups respectively with 1 normal control group and 6 experimental animal models of pulmonary fibrosis induced by bleomycin groups. For the pulmonary fibrosis model, bleomycin (BLM) was injected subcutaneously 8 times with a frequency of twice a week for 4 weeks. Furthermore, the mice were given CPL orally starting at week 6 of treatment with 2 different doses, 1.95mg (CPL-1) and 3.9mg (CPL) every day for 4 weeks. Pulmonary fibrosis histopathology was analyzed using HE and MT staining methods. Serum IL-6, KL-6, and TGF-β1 levels determination was carried out using the ELISA method. The administration of CPL significantly reduced the fibrosis score from 2.80±1.095 to 1.67±0.577µm (p=0.026). The CPL also showed anti-inflammatory activity by reducing IL-6 levels from 1916.20±594.27 to 16.81±17.07pg/mL (p=0.003); TGF-β1 levels from 51.25±2.25 to 22.48±0.93ng/mL (p=0.021); and KL-6 levels from 28.09±2.25 to 13.99±0.93ng/mL (p=0.000). CPL was proven to have pulmonary antifibrotic activity in experimental mice model. The pulmonary antifibrotic effect was evidenced by a decrease in pulmonary fibrosis scores also a decrease in KL-6 levels, IL-6 levels, and TGF-β1. The administration of CPL-1 and CPL-2 can provide recovery of pulmonary fibrosis induced by bleomycin.

Two cases of gastric cancer with elevated serum levels of KL-6

BackgroundThe serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6.Case presentationThe first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml.ConclusionsThese two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases.

The Role of SARS-CoV-2 Nucleocapsidic Antigen and Krebs von den Lungen 6 Serum Levels in Predicting COVID-19 Pneumonia Outcome.

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a significant threat worldwide, with severe cases leading to hospitalization and death. This study aims to evaluate the potential use of serum nucleocapsid antigen (NAg) and Krebs von den Lungen-6 glycoprotein (KL-6) as biomarkers of severe COVID-19 and to investigate their correlation with clinical, radiological, and biochemical parameters. This retrospective study included 128 patients with confirmed SARS-CoV-2 infection admitted to a Neapolitan hospital in Italy between October 2020 and July 2021. Demographic, clinical, and laboratory data were collected, including serum levels of NAg and KL-6. The Chung et al. Computed Tomography Severity Score (TSS) was used to assess the severity of pneumonia, and outcomes were classified as home discharge, rehabilitation, and death. Statistical analyses were performed to compare Group I (home discharge and rehabilitation) and Group II (death, sub-intensive care, and ICU stay) based on demographic data, laboratory parameters, and TSS. Group II patients showed worse outcomes with higher levels of NAg, KL-6, and inflammatory markers, including interleukin-6 (IL-6), interleukin-2 receptor (IL-2R), and adrenomedullin. TSS was also significantly higher in Group II, with a positive correlation between TSS and NAg and KL-6 levels. Group I patients had higher values of hemoglobin (Hb) and platelets (PLT), while Group II patients had higher values of C-reactive protein (CRP), procalcitonin (PCT), D-Dimer, and glycemia. No significant difference was observed in gender distribution. Serum NAg and KL-6 levels are potential biomarkers of severe COVID-19 pneumonia, with higher levels indicating greater inflammation and organ damage. NAg may help identify infected patients at an increased risk of severe COVID-19 and ensure their admission to the most appropriate level of care. KL-6 may help predict interstitial lung damage and the severity of clinical features. Further studies are needed to establish a decision-making cut-off for these biomarkers in COVID-19.

Role of BAL and Serum Krebs von den Lungen-6 (KL-6) in Patients with Pulmonary Fibrosis.

Background: Interstitial lung diseases (ILDs) encompass a diverse group of disorders affecting the lung interstitium, leading to inflammation, fibrosis, and impaired respiratory function. Currently, the identification of new diagnostic and prognostic biomarkers for ILDs turns out to be necessary. Several studies show the role of KL-6 in various types of interstitial lung disease and suggest that serum KL-6 levels can be used as a prognostic marker of disease. The aim of this study was to analyze KL-6 expression either in serum or bronchoalveolar lavage samples in order to: (i) make a serum vs. BAL comparison; (ii) better understand the local behavior of fibrosis vs. the systemic one; and (iii) evaluate any differences in patients with progressive fibrosis (PPF) versus patients with non-progressive fibrosis (nPPF). Methods: We used qRT-PCR to detect KL-6 expression both in serum and BAL samples. Mann-Whitney's U test was used to compare the differential expression between groups. Results: In serum, KL-6 is more highly expressed in PPF than in non-progressive fibrosis (p = 0.0295). This difference is even more significant in BAL (p < 0.001). Therefore, it is clear that KL-6 values are related to disease progression. Significant differences were found by making a comparison between BAL and serum. KL-6 was markedly higher in serum than BAL (p = 0.0146). Conclusions: This study identifies KL-6 as a promising biomarker for the severity of the fibrosing process and disease progression in ILDs, with significantly higher levels observed in PPF compared to nPPF. Moreover, the marked difference in KL-6 levels between serum and BAL emphasizes its potential diagnostic and prognostic relevance, providing enlightening insights into both the local and systemic aspects of ILDs.

Diagnostic Value of Serum KL-6 in Interstitial Lung Diseases.

To explore serum KL-6 level and investigate its diagnostic value in interstitial lung diseases (ILDs). Serum KL-6 level was measured using the chemiluminescent enzyme immunoassay. Statistical analysis was performed for determining the KL-6 concentration of each group. KL-6 level (U/mL) in the ILD group was 1388.321 ±1943.116, which was higher than that in the control group, showing a significant statistical difference. ROC curve analysis based on the receiver operating characteristic curve showed the optimal cut-off value of 402.5U/mL, sensitivity of 77.4%, specificity of 93.4%, and accuracy of 89.4%; through Chi-square test with the two groups, the positive rate of KL-6 in patients with ILD was proved to be significantly higher than that in the control group. KL-6 level was 1063.00±504.757 in the idiopathic pulmonary fibrosis (IPF) group, 1346.892 ±1827.252 in the connective tissue disease-associated interstitial lung disease (CTD-ILD) group, 467.889±288.859 in the organizing pneumonia (OP) group, 8252.333±6050.625 in the pulmonary alveolar proteinosis (PAP) group, and 359.200±392.707 in the sarcoidosis group. The rank sum test showed that the differences were statistically significant. KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group. Serum KL-6 level was confirmed to be highly sensitive, specific, and accurate in the diagnosis of ILD. Subgroup analysis showed that the KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.

KL-6 as a Tumor Marker of Primary Peritoneal Cancer in Patients with Connective Tissue Diseases.

We herein report two patients with connective tissue disease who developed primary peritoneal cancer (PPC). Serum Krebs von den Lungen-6 (KL-6) levels increased when PPC was diagnosed, and these levels were correlated with the treatment and worsening of PPC in both cases. In one patient with systemic sclerosis, serum KL-6 levels increased despite stable interstitial lung disease (ILD), leading to a diagnosis of PPC. In the other patient with dermatomyositis and no ILD, PPC was diagnosed with elevated KL-6 levels four months post-treatment, without ILD development. Clinicians should be reminded that KL-6 is a tumor marker in various cancers.