Serum interleukin-18 levels are specifically elevated in auto-inflammatory diseases involving the pyrin inflammasome: A study on 516 patients

Auto-inflammatory diseases (AIDs) are characterized by excessive activation of innate immunity. Current biomarkers, such as C-reactive protein (CRP) and serum Amyloid A (SAA), are not disease-specific and cannot reflect disease severity. Interleukin-18 (IL-18), a pro-inflammatory cytokine of the IL-1 superfamily, has been recently studied as, biomarker for AIDs; This study aims to evaluate total serum IL-18 levels in a large cohort of AID patients from the adult French national reference center for AID. We conducted a retrospective analysis of 708 IL-18 measurements from 516 patients. The highest IL-18 levels were observed in diseases involving the pyrin inflammasome, such as Familial Mediterranean fever, mevalonate kinase deficiency, CDC42-associated AID and PSTPIP1-associated AID. Receiver operating characteristic (ROC) curve analysis demonstrated an AUC of 0.87 for IL-18, with a sensitivity of 83.4 % and specificity of 76.2 % at a cut-off value of 412 pg/mL, in differentiating pyrin inflammasome-related diseases from other monogenic inflammatory diseases. Our findings suggest the utility of total serum IL-18 as a diagnostic tool, particularly for pyrin inflammasome-related AIDs, that could in the future help to personalized treatment strategies.