Prognostic role of blood KL-6 in rheumatoid arthritis–associated interstitial lung disease

Kim, Ho Cheol; Choi, Kwang Hun; Jacob, Joseph; Song, Jin Woo

doi:10.1371/journal.pone.0229997

Cited by 51 publications

(36 citation statements)

References 44 publications

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“…In our study, we show higher KL-6 concentrations in RA-ILD patients with lesion extension> 15% and in patients with the UIP pattern. In line with these results, a retrospective study performed on 84 RA-ILD patients, increased KL-6 levels were independently associated with a UIP pattern and were identified as an independent prognostic factor of mortality [18]. The degree of ILD progression on HRCT within 3 years was proportional to baseline serum KL-6 concentrations in the French subset of patients.…”

Section: Plos Onesupporting

confidence: 60%

Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease

Avouac¹,

Cauvet²,

Steelandt³

et al. 2020

PLoS ONE

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Objective To determine the performance of 3 circulating markers for the diagnosis and the progression of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). Methods Serum concentrations of 3 circulating markers, lung epithelial-derived surfactant protein D (SPD), chemokine CCL-18 and Krebs von den Lungen-6 glycoprotein (KL-6), were measured by ELISA in consecutive patients with established RA. These patients were recruited from 3 tertiary centers and they all had been investigated by chest high-resolution computed tomography (HRCT). For a subset of French patients, a follow-up HRCT was available (mean interval between HRCT: 3±1.5 years). Results Among the 147 included patients (age: 66 ± 12 years, 69% women, disease duration 11 ± 10 years), 40 (27%) had RA-ILD on chest HRCT. SPD, CCL18 and KL-6 concentrations were significantly higher in patients with RA-ILD. ROC curve analysis to assess the diagnostic abilities of the three markers for the diagnosis of RA-ILD showed a superiority of KL-6 (Area under the curve, AUC: 0.79 95% CI 0.72-0.86) compared to SPD (AUC: 0.66 95% CI 0.58-0.74) and CCL18 (AUC: 0.62, 95% CI 0.53-0.70). The sensitivity of KL-6 for the diagnosis of RA-ILD was 68% with a specificity of 83%. The combination of KL-6 with SPD and CCL18 improved its diagnostic ability, with increased sensitivity from 68% to 77%, specificity from 83% to 97%. Increased KL-6 levels were independently associated with the presence of RA-ILD after the adjustment on other RA-ILD risk factors. In the French subset with longitudinal data, baseline KL-6 serum levels were predictive of ILD progression and the degree of ILD progression on HRCT was proportional to baseline KL-6 concentrations.

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Section: Plos Onesupporting

confidence: 60%

Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease

Avouac¹,

Cauvet²,

Steelandt³

et al. 2020

PLoS ONE

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“…In particular, Krebs von den Lungen 6 (KL-6) could reflect the severity of ILD as assessed through HRCT and PFT parameters. Its potential role has been evaluated prevalently in Asian patients both in diagnosis and monitoring lung involvement [217,218]; a high value of KL-6 has been associated with mortality and usual interstitial pneumonia (UIP) pattern at HRCT [218]. Moreover, an increase of KL-6 has been associated with a progression of ILD over time as a possible marker of treatment response [139,219].…”

Section: Biomarkers and Response To Treatmentmentioning

confidence: 99%

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Cassone

Manfredi

Vacchi

et al. 2020

JCM

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Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

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“…KL-6 is considered to reflect the degree and severity of alveolar epithelial injury and might be a useful biomarker for predicting the prognosis of idiopathic pulmonary fibrosis (IPF) [ 10 – 12 ]. In recent years, numerous studies have focused on the relationship between KL-6 and ILD [ 13 , 14 ]. Lee et al found KL-6 levels were higher in RA-ILD than RA-no-ILD patients [ 15 ].…”

Section: Inroductionmentioning

confidence: 99%

Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

et al. 2021

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Introduction This study aimed to evaluate the role of tumor marker carbohydrate antigen (CA) 125 (CA125), CA19-9, carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Methods A retrospective analysis was performed. Fifty RA patients (24 patients with ILD and 26 patients without ILD), 10 healthy subjects and 14 patients with other connective tissue disease-associated interstitial lung disease were included. Serum levels of KL-6 and tumor markers CA19-9, CA125 and CEA were measured. Chest HRCT of patients with ILD was scored quantitatively according to the degree of fibrosis. Data on the C-reactive protein, erythrocyte sedimentation rate, rheumatoid factors and anti-cyclic peptide containing citrulline (anti-CCP) were also collected. Results Serum levels of KL-6, CA19-9, CA125 and CEA in the RA-ILD group were significantly higher than those in the RA-no-ILD group. The serum KL-6 level was positively correlated with the HRCT fibrosis score ( r = 0.63, p = 0.002). The logistic regression analysis showed that CA19-9 and smoking were associated with RA-ILD [OR = 1.118, 95% CI = (1.038, 1.204), p = 0.003 for CA19-9, OR = 14.969, 95% CI = (1.750, 128.043), p = 0.013 for smoking]. Conclusions KL-6 level and tumor markers were elevated in RA-ILD, and strongly associated with the severity of ILD, supporting their value as pathogenically relevant biomarkers, which can contribute to noninvasive detection of this extra-articular disease complication.

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Prognostic role of blood KL-6 in rheumatoid arthritis–associated interstitial lung disease

Cited by 51 publications

References 44 publications

Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease

Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

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