AB1191 KL-6 AND IL-18 AS DIAGNOSTIC MARKERS FOR INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS: OUTPERFORMING TRADITIONAL ASSESSMENTS FOR IMPROVED RISK STRATIFICATION AND EARLY DETECTION
Authors: C. Sieiro Santos, S. Calleja Antolín, J. De la Calle Lorenzo, M. Retuerto-Guerrero, C. Moriano, L. Sierra Herránz, E. Bollo de Miguel, P. Pérez-García, J. Ordas Martínez, P. Baenas González, C. Álvarez Castro, I. González, I. González Fernández, C. Díez, E. Diez Álvarez
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Despite advancements in SSc management, ILD remains the primary cause of death. Treating extensive or progressive SSc-ILD is crucial, but early identification and predicting progression risk are challenging. Recognizing high-risk cases for early intervention remains elusive, highlighting the urgent need for biomarkers. <h3>Objectives:</h3> The study aimed to assess the utility of serum biomarkers KL-6 and IL-18 in distinguishing different grades of fibrosis identified by semiquantitative CT extension in systemic sclerosis-associated interstitial lung disease (SSc-ILD), assess correlations with sociodemographic, immunological and clinical manifestations. Additionally, the research sought to compare the diagnostic performance of these biomarkers with traditional pulmonary function tests (FVC% and DLCO%). <h3>Methods:</h3> A cross-sectional study was conducted involving patients diagnosed with systemic sclerosis (SSc) based on the 2013 ACR/EULAR criteria. Patients were stratified based on disease duration and the presence of interstitial lung disease (ILD). All participants underwent baseline chest high-resolution computed tomography (HRCT) scans and pulmonary function tests. The serum concentrations of KL-6, IL8, and IL18BP were determined using quantitative ELISA techniques. The ILD extent was semiquantitatively graded via HRCT scans (grade 1: 0–20%; grade 2: &gt;20%). Extensive disease was defined as &gt;20% lung involvement on HRCT with FVC &lt;70% predicted, while limited lung involvement was defined as ≤20% ILD involvement on HRCT with FVC ≥70% predicted. The ELISA kits from MyBiosource (KL-6) and Invitrogen (IL8 and IL18BP) were employed for the analyses. <h3>Results:</h3> 74 patients were included, 27% were male. The mean age at diagnosis was 57.5±15 years and the mean time since diagnosis was 7.67±8 years. 28 patients had ILD (38%). 64 % of patients had &lt;20% ILD extent classified through HRCT scan. Correlation analysis revealed significant associations between serum levels of KL-6 (β=0.78, p=0.01) and IL-18 (β=0.62, p=0.03) and semiquantitative CT grade (Table 1). Significant correlation between IL-18 and skin involvement was found (β =0.43, p=0.0007). Receiver operating characteristic (ROC) analysis established optimal cut-off values for serum KL-6 (273.80 U/mL) and IL-18 (290.83 U/mL) in detecting ILD presence. The area under the curve (AUC) values for KL-6 and IL-18 outperformed FVC% and DLCO%, particularly in discriminating grade 2 from grade 1 ILD (Table 2 and Figure 1). <h3>Conclusion:</h3> The results demonstrated a significant correlation between KL-6 and IL-18 levels and semiquantitative CT grades, suggesting their utility as diagnostic markers for ILD in SSc patients. Notably, these biomarkers outperformed traditional pulmonary function tests in discriminating between ILD grades. The study highlights the promise of KL-6 and IL-18 for early detection and risk stratification in SSc-ILD, offering valuable insights for improved clinical management.REFERENCES: NIL. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>