Blood KL-6 predicts prognosis in primary Sjögren’s syndrome-associated interstitial lung disease

Kim, Yun Jae; Choe, Jooae; Moon, Su‐Jin; Song, Jin Woo

doi:10.1038/s41598-022-09283-w

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…Weng et al [28] compared the KL-6 levels in 69 pSS patients-among them, 59 complicated with ILD and 10 without-and found that KL-6 was one of the factors associated with the presence of ILD in patents with pSS. Serum KL-6 levels might also be a useful biomarker in predicting the prognosis of patients with pSS-ILD [29]. Zheng et al [30] conducted a retrospective study in patients with RA and found that serum KL-6 and tumor marker (CEA, CA153, and CA19-9) levels were elevated in patients with RA-ILD and were associated with ILD severity, supporting the clinical value of these markers as disease-related biomarkers.…”

Section: Discussionmentioning

confidence: 96%

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren’s Syndrome Complicated with Interstitial Lung Disease

Wei

Zhang

Yang

et al. 2023

JCM

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Objective: primary Sjögren’s syndrome (pSS) is an autoimmune disease, of which the most common complication is interstitial lung disease (ILD). This study aimed to analyze the clinical value of Krebs von den Lungen-6 (KL-6), carcinoembryonic antigen (CEA), and carbohydrate antigen 153(CA153) in patients with pSS complicated with ILD (pSS-ILD), given that only few studies have evaluated this. Methods: This is a cross-sectional study. Serum KL-6 levels (U/mL) were measured using chemiluminescence immunoassay, and concentrations of serum tumor markers were determined using the immunofluorescence method in 64 cases of pSS-ILD (pSS-ILD group), 23 cases without ILD (non-ILD group), and 45 healthy controls. The correlation between KL-6 and tumor markers as well as lung function was analyzed, and the factors that were associated with pSS-ILD were screened. Results: The serum KL-6 was more abnormally increased in patients with pSS-ILD, and the serum KL-6, CEA, carbohydrate antigen 125 (CA125), and CA153 levels were significantly higher in the pSS-ILD group than in the non-ILD and healthy control groups (p < 0.05). KL-6, CEA, and CA153 were negatively correlated with forced vital capacity (FVC%), forced expiratory volume in 1 s (FEV1%), total lung capacity (TLC%), and diffusing capacity for carbon monoxide (DLCO%) (all p < 0.05). Multivariate logistic analysis showed that KL-6 was an independent factor associated with pSS-ILD. Conclusions: In conclusion, we evaluated the association between clinical values of KL-6, tumor markers, and pSS-ILD, and found that KL-6 and tumor markers such as CEA, CA153, and CA125 in patients with pSS-ILD were higher than in patients with non-ILD, and KL-6 was more abnormally increased and significantly associated with ILD development in patients with pSS.

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Section: Discussionmentioning

confidence: 96%

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren’s Syndrome Complicated with Interstitial Lung Disease

Wei

Zhang

Yang

et al. 2023

JCM

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“…Type II pneumocytes in patients with ILD produce a mucin-like glycoprotein called KL-6 (71). The serum level of KL-6 correlates significantly with ILD prognosis and disease severity as defined by HRCT and is considered a potentially useful diagnostic marker for detecting asymptomatic SS-ILD patients (71)(72)(73).…”

Section: Treatmentmentioning

confidence: 99%

Immune-mediated lung diseases: A narrative review

Sweis

Alnaimat

et al. 2023

Front. Med.

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The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

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“…Nevertheless, research examining the correlation between serum KL-6 levels and mortality risk in patients with CTD-ILD has yielded conflicting results (19). While some studies have suggested that elevated baseline levels of serum KL-6 may be indicative of an increased mortality risk in individuals with CTD-ILD (20)(21)(22)(23)(24)(25)(26), others have not found a significant association (27)(28)(29)(30). Therefore, in this study, we performed a meta-analysis to systematically evaluate the association between serum KL-6 and mortality of patients with CTD-ILD.…”

Section: Introductionmentioning

confidence: 99%

Serum KL-6 and the mortality of patients with connective tissue disease-associated interstitial lung disease: A meta-analysis

Hong,

Yin,

Yan

et al. 2024

Biomol Biomed

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Connective tissue disease-associated interstitial lung disease (CTD-ILD) is an important underlying cause of morbidity and mortality in patients with CTD. Serum Krebs von den Lungen-6 (KL-6) is an immune factor which has been related to the severity of ILD. This systematic review and meta-analysis aimed to evaluate the association between serum KL-6 and mortality of patients with CTD-ILD. Longitudinal studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Fifteen cohorts involving 1737 patients with CTD-ILD were included. During a mean follow-up of 35.3 months, 430 (24.8%) patients died. Compared to those with a lower KL-6 at admission, patients with a higher KL-6 were associated with a higher mortality risk during follow-up (risk ratio: 2.18, 95% confidence interval: 1.66 to 2.87, P < 0.001; I2 = 20%). Subgroup analysis showed a significant association in studies from Asian countries, but not in those from non-Asian countries; in studies with cutoff of KL-6 derived in receiver operating characteristic (ROC) curve analysis, but not in those derived from other methods; in studies with multivariate analysis, but not in those with univariate analysis (P for subgroup difference all < 0.05). The association was not significantly affected by different CTDs or methods for measuring serum KL-6. In conclusion, a high serum KL-6 may be a risk factor of increased mortality in patients with CTD-ILD.

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Blood KL-6 predicts prognosis in primary Sjögren’s syndrome-associated interstitial lung disease

Cited by 9 publications

References 42 publications

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren’s Syndrome Complicated with Interstitial Lung Disease

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren’s Syndrome Complicated with Interstitial Lung Disease

Immune-mediated lung diseases: A narrative review

Serum KL-6 and the mortality of patients with connective tissue disease-associated interstitial lung disease: A meta-analysis

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