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

Abstract

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.

Krebs von den Lungen‐6, a promising marker in evaluating the severity of interstitial lung disease in Egyptian rheumatoid arthritis patients

“…Thus, during the inflammatory and regenerative process of ILD, KL-6 increases reflecting alveolar epithelial cells damages. 20 Our findings are consistent with those reported by several studies. Avouac et al, 2020 20 assessed KL-6 levels in 40 RA patients with ILD and 107 RA patients without ILD and reported higher levels of KL-6 in RA patients with ILD compared to RA without ILD.…”

“…Hence, finding reliable circulating biomarkers may aid in earlier diagnosis and clinical assessment of these cases. 19,20 KL-6 is being intensively investigated as a circulating biomarker in the context of ILD, 21,22 ILD associated with connective tissue diseases (CTD-ILD), 16,23,24 ILD associated with systemic sclerosis 19,25 and ILD associated with RA. 20,[26][27][28] In this study, we assessed the levels of KL-6 in 89 RA patients; 25 patients without ILD and 64 patients with ILD and evaluated the performance of KL-6 in diagnosis of ILD.…”

“…19,20 KL-6 is being intensively investigated as a circulating biomarker in the context of ILD, 21,22 ILD associated with connective tissue diseases (CTD-ILD), 16,23,24 ILD associated with systemic sclerosis 19,25 and ILD associated with RA. 20,[26][27][28] In this study, we assessed the levels of KL-6 in 89 RA patients; 25 patients without ILD and 64 patients with ILD and evaluated the performance of KL-6 in diagnosis of ILD. Results revealed higher levels of serum KL-6 in RA patients with ILD compared to those without ILD.…”

The role of lung ultrasound B-lines and serum KL-6 in the screening and follow-up of rheumatoid arthritis patients for an identification of interstitial lung disease: review of the literature, proposal for a preliminary algorithm, and clinical application to cases

“…KL-6 concentrations were significantly higher in patients with ILD compared to those without ILD and showing a correlation to the ILD course [ 70 , 71 ]. Furthermore, KL-6 had predictive value for the development and progression of ILD [ 72 – 75 ]. High KL-6 levels (≥ 640 U/mL) were independently associated with a UIP pattern (OR, 5.173; p = 0.05) in RA-ILD [ 76 ].…”

Rheumatoid Arthritis Interstitial Lung Disease: Measuring and Predictive Factors Among Patients Treated in Rehabilitation Clinics at Royal Medical Services

“…The results indicated that KL-6 is an appropriate marker for the diagnosis and development of RA-ILD. RA-ILD shares some genetic and phenotypic similarities with other fibrotic diseases including idiopathic pulmonary fibrosis, supporting the use of the same drugs in these conditions [ 15 , 16 ].…”